Tag Archives: aging

Comfort, Texas, the Timeship and Technological Immortality

Timeship-screenshot

There’s a small town deep in the heart of Texas’ Hill Country called Comfort. It was founded in the mid-19th century by German immigrants. Its downtown area is held to be one of the most well-preserved historic business districts in Texas. Now, just over 160 years on there’s another preservation effort underway in Comfort.

This time, however, the work goes well beyond preserving buildings; Comfort may soon be the global hub for life-extension research and human cryopreservation. The ambitious, and not without controversy, project is known as the Timeship, and is the brainchild of architect Stephen Valentine and the Stasis Foundation.

Since one the the key aims of the Timeship is to preserve biological material — DNA, tissue and organ samples, and even cryopreserved humans — the building design presents some rather unique and stringent challenges. The building must withstand a nuclear blast or other attack; its electrical and mechanical systems must remain functional and stable for hundreds of years; it must be self-sustaining and highly secure.

Read more about the building and much more about the Timeship here.

Image: Timeship screenshot. Courtesy of Timeship.

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Steps of Life

Steps-of-life-19th-century-print

Are you adolescent or middle-aged? Are you on life’s upwardly mobile journey towards the peak years (whatever these may be) or are you spiraling downwards in terminal decline?

The stages of life — from childhood to death — may be the simplistic invention of ancient scholars who sought a way to classify and explain the human condition, but over hundreds of years authors and artists have continued to be drawn to the subject. Our contemporary demographers and market researchers are just the latest in a long line of those who seek to explain, and now monetize, particular groups by age.

So, if you’re fascinated by this somewhat arbitrary chronological classification system the Public Domain Review has a treat. They’ve assembled a fine collection of images from the last five hundred years that depict the different ages of man and woman.

A common representation is to show ages ascending a series of steps from infancy to a peak and then descending towards old-age, senility and death. The image above is a particularly wonderful example of the genre and while the ages are noted in French the categories are not difficult to decipher:

20 years: “Jeunesse”

40 years: “Age de discretion”

50 years: “Age de Maturité”

90 years: “Age de decrépitude”

Image: “Le cours de la vie de l’homme dans ses différents âges”. Early 19th-century print showing stages of life at ten year intervals from 10-90 years as ascending and then descending steps. Courtesy: Wikipedia. Public Domain.

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Pass the Nicotinamide Adenine Dinucleotide

NAD-moleculeFor those of us seeking to live another 100 years or more the news and/or hype over the last decade belonged to resveratrol. The molecule is believed to improve functioning of specific biochemical pathways in the cell, which may improve cell repair and hinder the aging process. Resveratrol is found — in trace amounts — in grape skin (and hence wine), blueberries and raspberries. While proof remains scarce, this has not stopped the public from consuming large quantities of wine and berries.

Ironically, one would need to ingest such large amounts of resveratrol to replicate the benefits found in mice studies, that the wine alone would probably cause irreversible liver damage before any health benefits appeared. Oh well.

So, on to the next big thing, since aging cannot wait. It’s called NAD or Nicotinamide Adenine Dinucleotide. NAD performs several critical roles in the cell, one of which is energy metabolism. As we age our cells show diminishing levels of NAD and this is, possibly, linked to mitochondrial deterioration. Mitochondria are the cells’ energy factories, so keeping our mitochondria humming along is critical. Thus, hordes of researchers are now experimenting with NAD and related substances to see if they hold promise in postponing cellular demise.

From Scientific American:

Whenever I see my 10-year-old daughter brimming over with so much energy that she jumps up in the middle of supper to run around the table, I think to myself, “those young mitochondria.”

Mitochondria are our cells’ energy dynamos. Descended from bacteria that colonized other cells about 2 billion years, they get flaky as we age. A prominent theory of aging holds that decaying of mitochondria is a key driver of aging. While it’s not clear why our mitochondria fade as we age, evidence suggests that it leads to everything from heart failure to neurodegeneration, as well as the complete absence of zipping around the supper table.

Recent research suggests it may be possible to reverse mitochondrial decay with dietary supplements that increase cellular levels of a molecule called NAD (nicotinamide adenine dinucleotide). But caution is due: While there’s promising test-tube data and animal research regarding NAD boosters, no human clinical results on them have been published.

NAD is a linchpin of energy metabolism, among other roles, and its diminishing level with age has been implicated in mitochondrial deterioration. Supplements containing nicotinamide riboside, or NR, a precursor to NAD that’s found in trace amounts in milk, might be able to boost NAD levels. In support of that idea, half a dozen Nobel laureates and other prominent scientists are working with two small companies offering NR supplements.

The NAD story took off toward the end of 2013 with a high-profile paper by Harvard’s David Sinclair and colleagues. Sinclair, recall, achieved fame in the mid-2000s for research on yeast and mice that suggested the red wine ingredient resveratrol mimics anti-aging effects of calorie restriction. This time his lab made headlines by reporting that the mitochondria in muscles of elderly mice were restored to a youthful state after just a week of injections with NMN (nicotinamide mononucleotide), a molecule that naturally occurs in cells and, like NR, boosts levels of NAD.

It should be noted, however, that muscle strength was not improved in the NMN-treated micethe researchers speculated that one week of treatment wasn’t enough to do that despite signs that their age-related mitochondrial deterioration was reversed.

NMN isn’t available as a consumer product. But Sinclair’s report sparked excitement about NR, which was already on the market as a supplement called Niagen. Niagen’s maker, ChromaDex, a publicly traded Irvine, Calif., company, sells it to various retailers, which market it under their own brand names. In the wake of Sinclair’s paper, Niagen was hailed in the media as a potential blockbuster.

In early February, Elysium Health, a startup cofounded by Sinclair’s former mentor, MIT biologist Lenny Guarente, jumped into the NAD game by unveiling another supplement with NR. Dubbed Basis, it’s only offered online by the company. Elysium is taking no chances when it comes to scientific credibility. Its website lists a dream team of advising scientists, including five Nobel laureates and other big names such as the Mayo Clinic’s Jim Kirkland, a leader in geroscience, and biotech pioneer Lee Hood. I can’t remember a startup with more stars in its firmament.

A few days later, ChromaDex reasserted its first-comer status in the NAD game by announcing that it had conducted a clinical trial demonstrating that a single dose of NR resulted in statistically significant increases in NAD in humansthe first evidence that supplements could really boost NAD levels in people. Details of the study won’t be out until it’s reported in a peer-reviewed journal, the company said. (ChromaDex also brandishes Nobel credentials: Roger Kornberg, a Stanford professor who won the Chemistry prize in 2006, chairs its scientific advisory board. Hes the son of Nobel laureate Arthur Kornberg, who, ChromaDex proudly notes, was among the first scientists to study NR some 60 years ago.)

The NAD findings tie into the ongoing story about enzymes called sirtuins, which Guarente, Sinclair and other researchers have implicated as key players in conferring the longevity and health benefits of calorie restriction. Resveratrol, the wine ingredient, is thought to rev up one of the sirtuins, SIRT1, which appears to help protect mice on high doses of resveratrol from the ill effects of high-fat diets. A slew of other health benefits have been attributed to SIRT1 activation in hundreds of studies, including several small human trials.

Here’s the NAD connection: In 2000, Guarente’s lab reported that NAD fuels the activity of sirtuins, including SIRT1the more NAD there is in cells, the more SIRT1 does beneficial things. One of those things is to induce formation of new mitochondria. NAD can also activate another sirtuin, SIRT3, which is thought to keep mitochondria running smoothly.

Read the entire article here.

Image: Structure of nicotinamide adenine dinucleotide, oxidized (NAD+). Courtesy of Wikipedia. Public Domain.

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On the Joys of Not Being Twenty Again

I’m not twenty, and am constantly reminded that I’m not — both from internal alerts and external messages. Would I like to be younger? Of course. But it certainly comes at a price. So, after reading the exploits of a 20-something forced to live without her smartphone for a week, I realize it’s not all that bad being a cranky old luddite.

I hope that the ordeal, excerpted below, is tongue-very-much-in-cheek but I suspect it’s not: constant status refreshes, morning selfies, instant content gratification, nano-scale attention span, over-stimulation, life-stream documentation, peer ranking, group-think, interrupted interruptions. Thus, I realize I’m rather content not to be twenty after all.

From the Telegraph:

I have a confession to make: I am addicted to my smartphone. I use it as an alarm clock, map, notepad, mirror and camera.

I spend far too much time on Twitter and Instagram and have this week realised I have a nervous tick where I repeatedly unlock my smartphone.

And because of my phone’s many apps which organise my life and help me navigate the world, like many people my age, I am quite literally lost without it.

I am constantly told off by friends and family for using my phone during conversations, and I recently found out (to my horror) that I have taken over 5,000 selfies.

So when my phone broke I seized the opportunity to spend an entire week without it, and kept a diary each day.

Day One: Thursday

Frazzled, I reached to my bedside table, so I could take a morning selfie and send it to my friends.

Realising why that could not happen, my hand and my heart both felt empty. I knew at this point it was going to be a long week.

Day Two: Friday

I basked in the fact my colleagues could not contact me – and if I did not reply to their emails straight away it would not be the end of the world.

I then took the train home to see my parents outside London.

I couldn’t text my mother about any delays which may have happened (they didn’t), and she couldn’t tell me if she was going to be late to the station (she wasn’t). The lack of phone did nothing but make me feel anxious and prevent me from being able to tweet about the irritating children screaming on the train.

Day Three: Saturday

It is a bit weird feeling completely cut off from the outside world; I am not chained to my computer like I am at work and I am not allowed to constantly be on my laptop like a teen hacker.

It was nice though – a real detox. We went on a walk with our spaniel in the countryside near the Chiltern Hills. I had to properly talk to everyone, instead of constantly refreshing Twitter, which was novel.

I do feel like my attention span is improving every day, but I equally feel anchorless and lost without having any way of contacting anyone, or documenting my life.

….

Day Seven: Wednesday

My attention span and patience have grown somewhat, and I have noticed I daydream and have thoughts independent of Twitter far more often than usual.

Read the entire account here.

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Forget Broccoli. It’s All About the Blue Zones

You should know how to live to be 100 years old by now. Tip number one: inherit good genes. Tip number two: forget uploading your consciousness to an AI, for now. Tip number three: live and eat in a so-called Blue Zone. Tip number four: walk fast, eat slowly.

From the NYT:

Dan Buettner and I were off to a good start. He approved of coffee.

“It’s one of the biggest sources of antioxidants in the American diet,” he said with chipper confidence, folding up his black Brompton bike.

As we walked through Greenwich Village, looking for a decent shot of joe to fuel an afternoon of shopping and cooking and talking about the enigma of longevity, he pointed out that the men and women of Icaria, a Greek island in the middle of the Aegean Sea, regularly slurp down two or three muddy cups a day.

This came as delightful news to me. Icaria has a key role in Mr. Buettner’s latest book, “The Blue Zones Solution,” which takes a deep dive into five places around the world where people have a beguiling habit of forgetting to die. In Icaria they stand a decent chance of living to see 100. Without coffee, I don’t see much point in making it to 50.

The purpose of our rendezvous was to see whether the insights of a longevity specialist like Mr. Buettner could be applied to the life of a food-obsessed writer in New York, a man whose occupational hazards happen to include chicken wings, cheeseburgers, martinis and marathon tasting menus.

Covering the world of gastronomy and mixology during the era of David Chang (career-defining dish: those Momofuku pork-belly buns) and April Bloomfield (career-defining dish: the lamb burger at the Breslin Bar and Dining Room) does not exactly feel like an enterprise that’s adding extra years to my life — or to my liver.

And the recent deaths (even if accidental) of men in my exact demographic — the food writer Joshua Ozersky, the tech entrepreneur Dave Goldberg — had put me in a mortality-anxious frame of mind.

With my own half-century mark eerily visible on the horizon, could Mr. Buettner, who has spent the last 10 years unlocking the mysteries of longevity, offer me a midcourse correction?

To that end, he had decided to cook me something of a longevity feast. Visiting from his home in Minnesota and camped out at the townhouse of his friends Andrew Solomon and John Habich in the Village, this trim, tanned, 55-year-old guru of the golden years was geared up to show me that living a long time was not about subsisting on a thin gruel of, well, gruel.

After that blast of coffee, which I dutifully diluted with soy milk (as instructed) at O Cafe on Avenue of the Americas, Mr. Buettner and I set forth on our quest at the aptly named LifeThyme market, where signs in the window trumpeted the wonders of wheatgrass. He reassured me, again, by letting me know that penitent hedge clippings had no place in our Blue Zones repast.

“People think, ‘If I eat more of this, then it’s O.K. to eat more burgers or candy,’ ” he said. Instead, as he ambled through the market dropping herbs and vegetables into his basket, he insisted that our life-extending banquet would hinge on normal affordable items that almost anyone can pick up at the grocery store. He grabbed fennel and broccoli, celery and carrots, tofu and coconut milk, a bag of frozen berries and a can of chickpeas and a jar of local honey.

The five communities spotlighted in “The Blue Zones Solution” (published by National Geographic) depend on simple methods of cooking that have evolved over centuries, and Mr. Buettner has developed a matter-of-fact disregard for gastro-trends of all stripes. At LifeThyme, he passed by refrigerated shelves full of vogue-ish juices in hues of green, orange and purple. He shook his head and said, “Bad!”

“The glycemic index on that is as bad as Coke,” he went on, snatching a bottle of carrot juice to scan the label. “For eight ounces, there’s 14 grams of sugar. People get suckered into thinking, ‘Oh, I’m drinking this juice.’ Skip the juicing. Eat the fruit. Or eat the vegetable.” (How about a protein shake? “No,” he said.)

So far, I was feeling pretty good about my chances of making it to 100. I love coffee, I’m not much of a juicer and I’ve never had a protein shake in my life. Bingo. I figured that pretty soon Mr. Buettner would throw me a dietary curveball (I noticed with vague concern that he was not putting any meat or cheese into his basket), but by this point I was already thinking about how fun it would be to meet my great-grandchildren.

I felt even better when he and I started talking about strenuous exercise, which for me falls somewhere between “root canal” and “Justin Bieber concert” on the personal aversion scale.

I like to go for long walks, and … well, that’s about it.

“That’s when I knew you’d be O.K.,” Mr. Buettner told me.

It turns out that walking is a popular mode of transport in the Blue Zones, too — particularly on the sun-splattered slopes of Sardinia, Italy, where many of those who make it to 100 are shepherds who devote the bulk of each day to wandering the hills and treating themselves to sips of red wine.

“A glass of wine is better than a glass of water with a Mediterranean meal,” Mr. Buettner told me.

Red wine and long walks? If that’s all it takes, people, you’re looking at Methuselah.

O.K., yes, Mr. Buettner moves his muscles a lot more than I do. He likes to go everywhere on that fold-up bike, which he hauls along with him on trips, and sometimes he does yoga and goes in-line skating. But he generally believes that the high-impact exercise mania as practiced in the major cities of the United States winds up doing as much harm as good.

“You can’t be pounding your joints with marathons and pumping iron,” he said. “You’ll never see me doing CrossFit.”

For that evening’s meal, Mr. Buettner planned to cook dishes that would make reference to the quintet of places that he focuses on in “The Blue Zones Solution”: along with Icaria and Sardinia, they are Okinawa, Japan; the Nicoya Peninsula in Costa Rica; and Loma Linda, Calif., where Seventh-day Adventists have a tendency to outlive their fellow Americans, thanks to a mostly vegetarian diet that is heavy on nuts, beans, oatmeal, 100 percent whole-grain bread and avocados.

We walked from the market to the townhouse. And it was here, as Mr. Buettner laid out his cooking ingredients on a table in Mr. Solomon’s and Mr. Habich’s commodious, state-of-the-art kitchen, that I noticed the first real disconnect between the lives of the Blue Zones sages and the life of a food writer who has enjoyed many a lunch hour scarfing down charcuterie, tapas and pork-belly-topped ramen at the Gotham West Market food court.

Where was the butter? Hadn’t some nice scientists determined that butter’s not so lethal for us, after all? (“My view is that butter, lard and other animal fats are a bit like radiation: a dollop a couple of times a week probably isn’t going to hurt you, but we don’t know the safe level,” Mr. Buettner later wrote in an email. “At any rate, I can send along a paper that largely refutes the whole ‘Butter is Back’ craze.” No, thanks, I’m good.)

Where was the meat? Where was the cheese? (No cheese? And here I thought we’d be friends for another 50 years, Mr. Buettner.)

Read the entire article here.

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Kodokushi. A Lonely Death

As we age many of us tend to ponder our legacies. We wonder if we did good throughout our lives; we wonder if we’ll be remembered. Then we die.

Some will pass on treasured mementos to their descendents, families and friends; others — usually the one percenters — will cast their names on buildings, art bequests, research funds, and academic chairs. And yet others may not entrust any physical objects to their survivors, but nonetheless they’ll leave behind even more significant artifacts: trails of goodwill, moral frameworks, positive behaviors and traits, sound knowledge and teachings, passion, wonder.

Some of us will die in our sleep. A few will die in accidents or at the hands of others. Many of us will die in hospitals or clinics, attached to our technologies, sometimes attended by nearest and dearest, sometimes attended only by clinicians.

Sadly, some will die alone. Paradoxically, despite our increasing technologically enabled interconnectedness this phenomenon is on the increase, especially in aging societies with a low birth rate. Japan is a striking example — to such an extent that the Japanese even have a word for it: kodokushi or “lonely death”. Sadder still, where there are kodokushi victims there are now removal companies dedicated to their cleanup.

From Roads and Kingdoms:

Three months ago in an apartment on the outskirts of Osaka, Japan, Haruki Watanabe died alone. For weeks his body slowly decomposed, slouched in its own fluids and surrounded by fetid, fortnight-old food. He died of self-neglect, solitude, and a suspected heart problem. At 60, Watanabe, wasn’t old, nor was he especially poor. He had no friends, no job, no wife, and no concerned children. His son hadn’t spoken to him in years, nor did he want to again.

For three months no one called, no one knew, no one cared. For three months Watanabe rotted in his bedsheets, alongside pots of instant ramen and swarming cockroaches. The day that someone eventually called, he came not out of concern but out of administration. Watanabe had run out of money, and his bank had stopped paying the rent. The exasperated landlord, Toru Suzuki, had rung and rung, but no one had picked up. Sufficiently angry, he made the trip from his own home, in downtown Osaka, to the quiet suburb where his lodger lived. (Both men’s names are pseudonyms.)

First, there was the smell, a thick, noxious sweetness oozing from beneath the door frame. Second, there was the sight, the shape of a mortally slumped corpse beneath urine-soaked bedsheets. Third, there was the reality: Suzuki had come to collect his dues but had instead found his tenant’s dead body.

Disgusted, angry, but mostly shocked that this could happen to him, the landlord rang the police. The police came; they investigated with procedural dispassion and declared the death unsuspicious. This wasn’t suicide in the traditional sense, they said, but it did seem that the deceased had wanted to die. They’d seen it before, and it was an increasingly common occurrence throughout Japan: a single man dying, essentially, from loneliness.

They noted down what was required by their forms, wrapped up the body in officialdom, tied it with red tape, and removed it amid gawps and gags of inquisitive neighbors. The police then departed for the cemetery, where, because no family member had stepped forward to claim the body, they would intern Watanabe in an unmarked grave alongside the rest of Japan’s forgotten dead.

Suzuki was now left to his festering property and precarious financials. He was concerned. He didn’t know who to call or how to deal with the situation. In Japan, suicide can dramatically reduce the value of a property, and although this wasn’t suicide, his neighbors had seen enough; the gossip would spread fast. He heard whispers of kodokushi, a word bandied about since the Great Hanshin earthquake in 1995, when thousands of elderly Japanese were relocated to different residences and started dying alone, ostracized or isolated from family and friends. But what did that really mean for Suzuki, and how was he going to deal with it? Like most Japanese, he had heard of the “lonely death” but had not really believed in it; he certainly didn’t know what to do in such circumstances. So he turned to the Internet, and after hours of fruitless searching found a company called Risk-Benefit, run by a man named Toru Koremura.

With no other options he picked up the phone and gave the company a call.

With one of the fastest aging populations in the world and traditional family structures breaking down, Japan’s kodokushi phenomenon is becoming harder to ignore—not that the government and the Japanese people don’t do their best to sweep it under the carpet. Inaccurate statistics abound, with confusing definitions of what is and isn’t considered kodokushi being created in the process. According to the Ministry of Health, Labour and Welfare, there were some 3,700 “unaccompanied deaths” in Japan in 2013. However, other experts estimate the number is nearer 30,000 a year.

Scott North, a sociologist at Osaka University, argues that this extreme divergence could be the result of experts including some forms of suicide (of which there are around 27,000 cases a year in Japan) into the category of kodokushi. It could also be the result of bad accounting. Recently, senior Japanese bureaucrats admitted to having lost track of more than 250,000 people older than age 100. In a case that made international headlines in 2010, Sogen Kato, thought to be Tokyo’s oldest man at 111 years of age, turned out to have been mummified in his own apartment for more than 30 years.

Read the entire story here.

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Thirty Going On Sixty or Sixty Going on Thirty?

By now you probably realize that I’m a glutton for human research studies. I’m particularly fond of studies that highlight a particular finding one week, only to be contradicted by the results of another study the following week.

However, despite lack of contradictions, this one published via the Proceedings of the National Academy of Sciences caught my eye. It suggests that we age at remarkably different rates. While most subjects showed a perceived, biological age within a handful of years of their actual, chronological age, there were some surprises. Some 30-year-olds showed a biological age twice that of their chronological age, while some appeared ten years younger.

From the BBC:

A study of people born within a year of each other has uncovered a huge gulf in the speed at which their bodies age.

The report, in Proceedings of the National Academy of Sciences, tracked traits such as weight, kidney function and gum health.

Some of the 38-year-olds were ageing so badly that their “biological age” was on the cusp of retirement.

The team said the next step was to discover what was affecting the pace of ageing.

The international research group followed 954 people from the same town in New Zealand who were all born in 1972-73.

The scientists looked at 18 different ageing-related traits when the group turned 26, 32 and 38 years old.

The analysis showed that at the age of 38, the people’s biological ages ranged from the late-20s to those who were nearly 60.

“They look rough, they look lacking in vitality,” said Prof Terrie Moffitt from Duke University in the US.

The study said some people had almost stopped ageing during the period of the study, while others were gaining nearly three years of biological age for every twelve months that passed.

People with older biological ages tended to do worse in tests of brain function and had a weaker grip.

Most people’s biological age was within a few years of their chronological age. It is unclear how the pace of biological ageing changes through life with these measures.

Read the entire story here.

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Syndrome X

DNA_Structure

The quest for immortality or even great longevity has probably led humans since they first became self-aware. Entire cultural movements and industries are founded on the desire to enhance and extend our lives. Genetic research, of course, may eventually unlock some or all of life and death’s mysteries. In the meantime, groups of dedicated scientists continue to look for for the foundation of aging with a view to understanding the process and eventually slowing (and perhaps stopping) it. Richard Walker is one of these singularly focused researchers.

From the BBC:

Richard Walker has been trying to conquer ageing since he was a 26-year-old free-loving hippie. It was the 1960s, an era marked by youth: Vietnam War protests, psychedelic drugs, sexual revolutions. The young Walker relished the culture of exultation, of joie de vivre, and yet was also acutely aware of its passing. He was haunted by the knowledge that ageing would eventually steal away his vitality – that with each passing day his body was slightly less robust, slightly more decayed. One evening he went for a drive in his convertible and vowed that by his 40th birthday, he would find a cure for ageing.

Walker became a scientist to understand why he was mortal. “Certainly it wasn’t due to original sin and punishment by God, as I was taught by nuns in catechism,” he says. “No, it was the result of a biological process, and therefore is controlled by a mechanism that we can understand.”

Scientists have published several hundred theories of ageing, and have tied it to a wide variety of biological processes. But no one yet understands how to integrate all of this disparate information.

Walker, now 74, believes that the key to ending ageing may lie in a rare disease that doesn’t even have a real name, “Syndrome X”. He has identified four girls with this condition, marked by what seems to be a permanent state of infancy, a dramatic developmental arrest. He suspects that the disease is caused by a glitch somewhere in the girls’ DNA. His quest for immortality depends on finding it.

It’s the end of another busy week and MaryMargret Williams is shuttling her brood home from school. She drives an enormous SUV, but her six children and their coats and bags and snacks manage to fill every inch. The three big kids are bouncing in the very back. Sophia, 10, with a mouth of new braces, is complaining about a boy-crazy friend. She sits next to Anthony, seven, and Aleena, five, who are glued to something on their mother’s iPhone. The three little kids squirm in three car seats across the middle row. Myah, two, is mining a cherry slushy, and Luke, one, is pawing a bag of fresh crickets bought for the family gecko.

Finally there’s Gabrielle, who’s the smallest child, and the second oldest, at nine years old. She has long, skinny legs and a long, skinny ponytail, both of which spill out over the edges of her car seat. While her siblings giggle and squeal, Gabby’s dusty-blue eyes roll up towards the ceiling. By the calendar, she’s almost an adolescent. But she has the buttery skin, tightly clenched fingers and hazy awareness of a newborn.

Back in 2004, when MaryMargret and her husband, John, went to the hospital to deliver Gabby, they had no idea anything was wrong. They knew from an ultrasound that she would have clubbed feet, but so had their other daughter, Sophia, who was otherwise healthy. And because MaryMargret was a week early, they knew Gabby would be small, but not abnormally so. “So it was such a shock to us when she was born,” MaryMargret says.

Gabby came out purple and limp. Doctors stabilised her in the neonatal intensive care unit and then began a battery of tests. Within days the Williamses knew their new baby had lost the genetic lottery. Her brain’s frontal lobe was smooth, lacking the folds and grooves that allow neurons to pack in tightly. Her optic nerve, which runs between the eyes and the brain, was atrophied, which would probably leave her blind. She had two heart defects. Her tiny fists couldn’t be pried open. She had a cleft palate and an abnormal swallowing reflex, which meant she had to be fed through a tube in her nose. “They started trying to prepare us that she probably wouldn’t come home with us,” John says. Their family priest came by to baptise her.

Day after day, MaryMargret and John shuttled between Gabby in the hospital and 13-month-old Sophia at home. The doctors tested for a few known genetic syndromes, but they all came back negative. Nobody had a clue what was in store for her. Her strong Catholic family put their faith in God. “MaryMargret just kept saying, ‘She’s coming home, she’s coming home’,” recalls her sister, Jennie Hansen. And after 40 days, she did.

Gabby cried a lot, loved to be held, and ate every three hours, just like any other newborn. But of course she wasn’t. Her arms would stiffen and fly up to her ears, in a pose that the family nicknamed her “Harley-Davidson”. At four months old she started having seizures. Most puzzling and problematic, she still wasn’t growing. John and MaryMargret took her to specialist after specialist: a cardiologist, a gastroenterologist, a geneticist, a neurologist, an ophthalmologist and an orthopaedist. “You almost get your hopes up a little – ’This is exciting! We’re going to the gastro doctor, and maybe he’ll have some answers’,” MaryMargret says. But the experts always said the same thing: nothing could be done.

The first few years with Gabby were stressful. When she was one and Sophia two, the Williamses drove from their home in Billings, Montana, to MaryMargret’s brother’s home outside of St Paul, Minnesota. For nearly all of those 850 miles, Gabby cried and screamed. This continued for months until doctors realised she had a run-of-the-mill bladder infection. Around the same period, she acquired a severe respiratory infection that left her struggling to breathe. John and MaryMargret tried to prepare Sophia for the worst, and even planned which readings and songs to use at Gabby’s funeral. But the tiny toddler toughed it out.

While Gabby’s hair and nails grew, her body wasn’t getting bigger. She was developing in subtle ways, but at her own pace. MaryMargret vividly remembers a day at work when she was pushing Gabby’s stroller down a hallway with skylights in the ceiling. She looked down at Gabby and was shocked to see her eyes reacting to the sunlight. “I thought, ‘Well, you’re seeing that light!’” MaryMargret says. Gabby wasn’t blind, after all.

Despite the hardships, the couple decided they wanted more children. In 2007 MaryMargret had Anthony, and the following year she had Aleena. By this time, the Williamses had stopped trudging to specialists, accepting that Gabby was never going to be fixed. “At some point we just decided,” John recalls, “it’s time to make our peace.”

Mortal questions

When Walker began his scientific career, he focused on the female reproductive system as a model of “pure ageing”: a woman’s ovaries, even in the absence of any disease, slowly but inevitably slide into the throes of menopause. His studies investigated how food, light, hormones and brain chemicals influence fertility in rats. But academic science is slow. He hadn’t cured ageing by his 40th birthday, nor by his 50th or 60th. His life’s work was tangential, at best, to answering the question of why we’re mortal, and he wasn’t happy about it. He was running out of time.

So he went back to the drawing board. As he describes in his book, Why We Age, Walker began a series of thought experiments to reflect on what was known and not known about ageing.

Ageing is usually defined as the slow accumulation of damage in our cells, organs and tissues, ultimately causing the physical transformations that we all recognise in elderly people. Jaws shrink and gums recede. Skin slacks. Bones brittle, cartilage thins and joints swell. Arteries stiffen and clog. Hair greys. Vision dims. Memory fades. The notion that ageing is a natural, inevitable part of life is so fixed in our culture that we rarely question it. But biologists have been questioning it for a long time.

It’s a harsh world out there, and even young cells are vulnerable. It’s like buying a new car: the engine runs perfectly but is still at risk of getting smashed on the highway. Our young cells survive only because they have a slew of trusty mechanics on call. Take DNA, which provides the all-important instructions for making proteins. Every time a cell divides, it makes a near-perfect copy of its three-billion-letter code. Copying mistakes happen frequently along the way, but we have specialised repair enzymes to fix them, like an automatic spellcheck. Proteins, too, are ever vulnerable. If it gets too hot, they twist into deviant shapes that keep them from working. But here again, we have a fixer: so-called ‘heat shock proteins’ that rush to the aid of their misfolded brethren. Our bodies are also regularly exposed to environmental poisons, such as the reactive and unstable ‘free radical’ molecules that come from the oxidisation of the air we breathe. Happily, our tissues are stocked with antioxidants and vitamins that neutralise this chemical damage. Time and time again, our cellular mechanics come to the rescue.

Which leads to the biologists’ longstanding conundrum: if our bodies are so well tuned, why, then, does everything eventually go to hell?

One theory is that it all boils down to the pressures of evolution. Humans reproduce early in life, well before ageing rears its ugly head. All of the repair mechanisms that are important in youth – the DNA editors, the heat shock proteins, the antioxidants – help the young survive until reproduction, and are therefore passed down to future generations. But problems that show up after we’re done reproducing cannot be weeded out by evolution. Hence, ageing.

Most scientists say that ageing is not caused by any one culprit but by the breakdown of many systems at once. Our sturdy DNA mechanics become less effective with age, meaning that our genetic code sees a gradual increase in mutations. Telomeres, the sequences of DNA that act as protective caps on the ends of our chromosomes, get shorter every year. Epigenetic messages, which help turn genes on and off, get corrupted with time. Heat shock proteins run down, leading to tangled protein clumps that muck up the smooth workings of a cell. Faced with all of this damage, our cells try to adjust by changing the way they metabolise nutrients and store energy. To ward off cancer, they even know how to shut themselves down. But eventually cells stop dividing and stop communicating with each other, triggering the decline we see from the outside.

Scientists trying to slow the ageing process tend to focus on one of these interconnected pathways at a time. Some researchers have shown, for example, that mice on restricted-calorie diets live longer than normal. Other labs have reported that giving mice rapamycin, a drug that targets an important cell-growth pathway, boosts their lifespan. Still other groups are investigating substances that restore telomeres, DNA repair enzymes and heat shock proteins.

During his thought experiments, Walker wondered whether all of these scientists were fixating on the wrong thing. What if all of these various types of cellular damages were the consequences of ageing, but not the root cause of it? He came up with an alternative theory: that ageing is the unavoidable fallout of our development.

The idea sat on the back burner of Walker’s mind until the evening of 23 October 2005. He was working in his home office when his wife called out to him to join her in the family room. She knew he would want to see what was on TV: an episode of Dateline about a young girl who seemed to be “frozen in time”. Walker watched the show and couldn’t believe what he was seeing. Brooke Greenberg was 12 years old, but just 13 pounds (6kg) and 27 inches (69cm) long. Her doctors had never seen anything like her condition, and suspected the cause was a random genetic mutation. “She literally is the Fountain of Youth,” her father, Howard Greenberg, said.

Walker was immediately intrigued. He had heard of other genetic diseases, such as progeria and Werner syndrome, which cause premature ageing in children and adults respectively. But this girl seemed to be different. She had a genetic disease that stopped her development and with it, Walker suspected, the ageing process. Brooke Greenberg, in other words, could help him test his theory.

Uneven growth

Brooke was born a few weeks premature, with many birth defects. Her paediatrician labeled her with Syndrome X, not knowing what else to call it.

After watching the show, Walker tracked down Howard Greenberg’s address. Two weeks went by before Walker heard back, and after much discussion he was allowed to test Brooke. He was sent Brooke’s medical records as well as blood samples for genetic testing. In 2009, his team published a brief report describing her case.

Walker’s analysis found that Brooke’s organs and tissues were developing at different rates. Her mental age, according to standardised tests, was between one and eight months. Her teeth appeared to be eight years old; her bones, 10 years. She had lost all of her baby fat, and her hair and nails grew normally, but she had not reached puberty. Her telomeres were considerably shorter than those of healthy teenagers, suggesting that her cells were ageing at an accelerated rate.

All of this was evidence of what Walker dubbed “developmental disorganisation”. Brooke’s body seemed to be developing not as a coordinated unit, he wrote, but rather as a collection of individual, out-of-sync parts. “She is not simply ‘frozen in time’,” Walker wrote. “Her development is continuing, albeit in a disorganised fashion.”

The big question remained: why was Brooke developmentally disorganised? It wasn’t nutritional and it wasn’t hormonal. The answer had to be in her genes. Walker suspected that she carried a glitch in a gene (or a set of genes, or some kind of complex genetic programme) that directed healthy development. There must be some mechanism, after all, that allows us to develop from a single cell to a system of trillions of cells. This genetic programme, Walker reasoned, would have two main functions: it would initiate and drive dramatic changes throughout the organism, and it would also coordinate these changes into a cohesive unit.

Ageing, he thought, comes about because this developmental programme, this constant change, never turns off. From birth until puberty, change is crucial: we need it to grow and mature. After we’ve matured, however, our adult bodies don’t need change, but rather maintenance. “If you’ve built the perfect house, you would want to stop adding bricks at a certain point,” Walker says. “When you’ve built a perfect body, you’d want to stop screwing around with it. But that’s not how evolution works.” Because natural selection cannot influence traits that show up after we have passed on our genes, we never evolved a “stop switch” for development, Walker says. So we keep adding bricks to the house. At first this doesn’t cause much damage – a sagging roof here, a broken window there. But eventually the foundation can’t sustain the additions, and the house topples. This, Walker says, is ageing.

Brooke was special because she seemed to have been born with a stop switch. But finding the genetic culprit turned out to be difficult. Walker would need to sequence Brooke’s entire genome, letter by letter.

That never happened. Much to Walker’s chagrin, Howard Greenberg abruptly severed their relationship. The Greenbergs have not publicly explained why they ended their collaboration with Walker, and declined to comment for this article.

Second chance

In August 2009, MaryMargret Williams saw a photo of Brooke on the cover of People magazine, just below the headline “Heartbreaking mystery: The 16-year-old baby”. She thought Brooke sounded a lot like Gabby, so contacted Walker.

After reviewing Gabby’s details, Walker filled her in on his theory. Testing Gabby’s genes, he said, could help him in his mission to end age-related disease – and maybe even ageing itself.

This didn’t sit well with the Williamses. John, who works for the Montana Department of Corrections, often interacts with people facing the reality of our finite time on Earth. “If you’re spending the rest of your life in prison, you know, it makes you think about the mortality of life,” he says. What’s important is not how long you live, but rather what you do with the life you’re given. MaryMargret feels the same way. For years she has worked in a local dermatology office. She knows all too well the cultural pressures to stay young, and wishes more people would embrace the inevitability of getting older. “You get wrinkles, you get old, that’s part of the process,” she says.

But Walker’s research also had its upside. First and foremost, it could reveal whether the other Williams children were at risk of passing on Gabby’s condition.

For several months, John and MaryMargret hashed out the pros and cons. They were under no illusion that the fruits of Walker’s research would change Gabby’s condition, nor would they want it to. But they did want to know why. “What happened, genetically, to make her who she is?” John says. And more importantly: “Is there a bigger meaning for it?”

John and MaryMargret firmly believe that God gave them Gabby for a reason. Walker’s research offered them a comforting one: to help treat Alzheimer’s and other age-related diseases. “Is there a small piece that Gabby could present to help people solve these awful diseases?” John asks. “Thinking about it, it’s like, no, that’s for other people, that’s not for us.” But then he thinks back to the day Gabby was born. “I was in that delivery room, thinking the same thing – this happens to other people, not us.”

Still not entirely certain, the Williamses went ahead with the research.

Amassing evidence

Walker published his theory in 2011, but he’s only the latest of many researchers to think along the same lines. “Theories relating developmental processes to ageing have been around for a very long time, but have been somewhat under the radar for most researchers,” says Joao Pedro de Magalhaes, a biologist at the University of Liverpool. In 1932, for example, English zoologist George Parker Bidder suggested that mammals have some kind of biological “regulator” that stops growth after the animal reaches a specific size. Ageing, Bidder thought, was the continued action of this regulator after growth was done.

Subsequent studies showed that Bidder wasn’t quite right; there are lots of marine organisms, for example, that never stop growing but age anyway. Still, his fundamental idea of a developmental programme leading to ageing has persisted.

For several years, Stuart Kim’s group at Stanford University has been comparing which genes are expressed in young and old nematode worms. It turns out that some genes involved in ageing also help drive development in youth.

Kim suggested that the root cause of ageing is the “drift”, or mistiming, of developmental pathways during the ageing process, rather than an accumulation of cellular damage.

Other groups have since found similar patterns in mice and primates. One study, for example, found that many genes turned on in the brains of old monkeys and humans are the same as those expressed in young brains, suggesting that ageing and development are controlled by some of the same gene networks.

Perhaps most provocative of all, some studies of worms have shown that shutting down essential development genes in adults significantly prolongs life. “We’ve found quite a lot of genes in which this happened – several dozen,” de Magalhaes says.

Nobody knows whether the same sort of developmental-programme genes exist in people. But say that they do exist. If someone was born with a mutation that completely destroyed this programme, Walker reasoned, that person would undoubtedly die. But if a mutation only partially destroyed it, it might lead to a condition like what he saw in Brooke Greenberg or Gabby Williams. So if Walker could identify the genetic cause of Syndrome X, then he might also have a driver of the ageing process in the rest of us.

And if he found that, then could it lead to treatments that slow – or even end – ageing? “There’s no doubt about it,” he says.

Public stage

After agreeing to participate in Walker’s research, the Williamses, just like the Greenbergs before them, became famous. In January 2011, when Gabby was six, the television channel TLC featured her on a one-hour documentary. The Williams family also appeared on Japanese television and in dozens of newspaper and magazine articles.

Other than becoming a local celebrity, though, Gabby’s everyday life hasn’t changed much since getting involved in Walker’s research. She spends her days surrounded by her large family. She’ll usually lie on the floor, or in one of several cushions designed to keep her spine from twisting into a C shape. She makes noises that would make an outsider worry: grunting, gasping for air, grinding her teeth. Her siblings think nothing of it. They play boisterously in the same room, somehow always careful not to crash into her. Once a week, a teacher comes to the house to work with Gabby. She uses sounds and shapes on an iPad to try to teach cause and effect. When Gabby turned nine, last October, the family made her a birthday cake and had a party, just as they always do. Most of her gifts were blankets, stuffed animals and clothes, just as they are every year. Her aunt Jennie gave her make-up.

Walker teamed up with geneticists at Duke University and screened the genomes of Gabby, John and MaryMargret. This test looked at the exome, the 2% of the genome that codes for proteins. From this comparison, the researchers could tell that Gabby did not inherit any exome mutations from her parents – meaning that it wasn’t likely that her siblings would be able to pass on the condition to their kids. “It was a huge relief – huge,” MaryMargret says.

Still, the exome screening didn’t give any clues as to what was behind Gabby’s disease. Gabby carries several mutations in her exome, but none in a gene that would make sense of her condition. All of us have mutations littering our genomes. So it’s impossible to know, in any single individual, whether a particular mutation is harmful or benign – unless you can compare two people with the same condition.

All girls

Luckily for him, Walker’s continued presence in the media has led him to two other young girls who he believes have the same syndrome. One of them, Mackenzee Wittke, of Alberta, Canada, is now five years old, with has long and skinny limbs, just like Gabby. “We have basically been stuck in a time warp,” says her mother, Kim Wittke. The fact that all of these possible Syndrome X cases are girls is intriguing – it could mean that the crucial mutation is on their X chromosome. Or it could just be a coincidence.

Walker is working with a commercial outfit in California to compare all three girls’ entire genome sequences – the exome plus the other 98% of DNA code, which is thought to be responsible for regulating the expression of protein-coding genes.

For his theory, Walker says, “this is do or die – we’re going to do every single bit of DNA in these girls. If we find a mutation that’s common to them all, that would be very exciting.”

But that seems like a very big if.

Most researchers agree that finding out the genes behind Syndrome X is a worthwhile scientific endeavour, as these genes will no doubt be relevant to our understanding of development. They’re far less convinced, though, that the girls’ condition has anything to do with ageing. “It’s a tenuous interpretation to think that this is going to be relevant to ageing,” says David Gems, a geneticist at University College London. It’s not likely that these girls will even make it to adulthood, he says, let alone old age.

It’s also not at all clear that these girls have the same condition. Even if they do, and even if Walker and his collaborators discover the genetic cause, there would still be a steep hill to climb. The researchers would need to silence the same gene or genes in laboratory mice, which typically have a lifespan of two or three years. “If that animal lives to be 10, then we’ll know we’re on the right track,” Walker says. Then they’d have to find a way to achieve the same genetic silencing in people, whether with a drug or some kind of gene therapy. And then they’d have to begin long and expensive clinical trials to make sure that the treatment was safe and effective. Science is often too slow, and life too fast.

End of life

On 24 October 2013, Brooke passed away. She was 20 years old. MaryMargret heard about it when a friend called after reading it in a magazine. The news hit her hard. “Even though we’ve never met the family, they’ve just been such a part of our world,” she says.

MaryMargret doesn’t see Brooke as a template for Gabby – it’s not as if she now believes that she only has 11 years left with her daughter. But she can empathise with the pain the Greenbergs must be feeling. “It just makes me feel so sad for them, knowing that there’s a lot that goes into a child like that,” she says. “You’re prepared for them to die, but when it finally happens, you can just imagine the hurt.”

Today Gabby is doing well. MaryMargret and John are no longer planning her funeral. Instead, they’re beginning to think about what would happen if Gabby outlives them. (Sophia has offered to take care of her sister.) John turned 50 this year, and MaryMargret will be 41. If there were a pill to end ageing, they say they’d have no interest in it. Quite the contrary: they look forward to getting older, because it means experiencing the new joys, new pains and new ways to grow that come along with that stage of life.

Richard Walker, of course, has a fundamentally different view of growing old. When asked why he’s so tormented by it, he says it stems from childhood, when he watched his grandparents physically and psychologically deteriorate. “There was nothing charming to me about sedentary old people, rocking chairs, hot houses with Victorian trappings,” he says. At his grandparents’ funerals, he couldn’t help but notice that they didn’t look much different in death than they did at the end of life. And that was heartbreaking. “To say I love life is an understatement,” he says. “Life is the most beautiful and magic of all things.”

If his hypothesis is correct – who knows? – it might one day help prevent disease and modestly extend life for millions of people. Walker is all too aware, though, that it would come too late for him. As he writes in his book: “I feel a bit like Moses who, after wandering in the desert for most years of his life, was allowed to gaze upon the Promised Land but not granted entrance into it.”

 Read the entire story here.

Story courtesy of BBC and Mosaic under Creative Commons License.

Image: DNA structure. Courtesy of Wikipedia.

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Good Mutations and Breathing

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Stem cells — the factories that manufacture all our component body parts — may hold a key to divining why our bodies gradually break down as we age. A new body of research shows how the body’s population of blood stem cells mutates, and gradually dies, over a typical lifespan. Sometimes these mutations turn cancerous, sometimes not. Luckily for us, the research is centered on the blood samples of Hendrikje van Andel-Schipper — she died in 2005 at the age of 115, and donated her body to science. Her body showed a remarkable resilience — no hardening of the arteries and no deterioration of her brain tissue.  When quizzed about the secret of her longevity, she once retorted, “breathing”.

From the New Scientist:

Death is the one certainty in life – a pioneering analysis of blood from one of the world’s oldest and healthiest women has given clues to why it happens.

Born in 1890, Hendrikje van Andel-Schipper was at one point the oldest woman in the world. She was also remarkable for her health, with crystal-clear cognition until she was close to death, and a blood circulatory system free of disease. When she died in 2005, she bequeathed her body to science, with the full support of her living relatives that any outcomes of scientific analysis – as well as her name – be made public.

Researchers have now examined her blood and other tissues to see how they were affected by age.

What they found suggests, as we could perhaps expect, that our lifespan might ultimately be limited by the capacity for stem cells to keep replenishing tissues day in day out. Once the stem cells reach a state of exhaustion that imposes a limit on their own lifespan, they themselves gradually die out and steadily diminish the body’s capacity to keep regenerating vital tissues and cells, such as blood.

Two little cells

In van Andel-Schipper’s case, it seemed that in the twilight of her life, about two-thirds of the white blood cells remaining in her body at death originated from just two stem cells, implying that most or all of the blood stem cells she started life with had already burned out and died.

“Is there a limit to the number of stem cell divisions, and does that imply that there’s a limit to human life?” asks Henne Holstege of the VU University Medical Center in Amsterdam, the Netherlands, who headed the research team. “Or can you get round that by replenishment with cells saved from earlier in your life?” she says.

The other evidence for the stem cell fatigue came from observations that van Andel-Schipper’s white blood cells had drastically worn-down telomeres – the protective tips on chromosomes that burn down like wicks each time a cell divides. On average, the telomeres on the white blood cells were 17 times shorter than those on brain cells, which hardly replicate at all throughout life.

The team could establish the number of white blood cell-generating stem cells by studying the pattern of mutations found within the blood cells. The pattern was so similar in all cells that the researchers could conclude that they all came from one of two closely related “mother” stem cells.

Point of exhaustion

“It’s estimated that we’re born with around 20,000 blood stem cells, and at any one time, around 1000 are simultaneously active to replenish blood,” says Holstege. During life, the number of active stem cells shrinks, she says, and their telomeres shorten to the point at which they die – a point called stem-cell exhaustion.

Holstege says the other remarkable finding was that the mutations within the blood cells were harmless – all resulted from mistaken replication of DNA during van Andel-Schipper’s life as the “mother” blood stem cells multiplied to provide clones from which blood was repeatedly replenished.

She says this is the first time patterns of lifetime “somatic” mutations have been studied in such an old and such a healthy person. The absence of mutations posing dangers of disease and cancer suggest that van Andel-Schipper had a superior system for repairing or aborting cells with dangerous mutations.

Read the entire article here.

Image: Hendrikje van Andel-Schipper, aged 113. Courtesy of Wikipedia.

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Fourteen Years in Four Minutes

Dutch filmmaker Frans Hofmeester has made a beautiful and enduring timelapse portrait. Shot over a period of 14 years, the video shows his daughter growing up before our eyes. To create this momentous documentary work Hofmeester filmed his daughter, Lotte, for 15 seconds every week since birth. This is a remarkable feat  for both filmmaker and his subject, and probably makes many of us wish we could have done the same. Hofmeester created a similar timelapse video of Lotte’s younger brother Vince.

Read more on this story here.

Video courtesy of Frans Hofmeester.

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Now Where Did I Put Those Keys?

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We all lose our car keys and misplace our cell phones. We leave umbrellas on public transport. We forget things at the office. We all do it — some more frequently than others. And, it’s not merely a symptom of aging. Many younger people seem to be increasingly prone to losing their personal items, perhaps a characteristic of their increasingly fragmented, distracted and limited attention spans.

From the WSJ:

You’ve put your keys somewhere and now they appear to be nowhere, certainly not in the basket by the door they’re supposed to go in and now you’re 20 minutes late for work. Kitchen counter, night stand, book shelf, work bag: Wait, finally, there they are under the mail you brought in last night.

Losing things is irritating and yet we are a forgetful people. The average person misplaces up to nine items a day, and one-third of respondents in a poll said they spend an average of 15 minutes each day searching for items—cellphones, keys and paperwork top the list, according to an online survey of 3,000 people published in 2012 by a British insurance company.

Everyday forgetfulness isn’t a sign of a more serious medical condition like Alzheimer’s or dementia. And while it can worsen with age, minor memory lapses are the norm for all ages, researchers say.

Our genes are at least partially to blame, experts say. Stress, fatigue, and multitasking can exacerbate our propensity to make such errors. Such lapses can also be linked to more serious conditions like depression and attention-deficit hyperactivity disorders.

“It’s the breakdown at the interface of attention and memory,” says Daniel L. Schacter, a psychology professor at Harvard University and author of “The Seven Sins of Memory.”

That breakdown can occur in two spots: when we fail to activate our memory and encode what we’re doing—where we put down our keys or glasses—or when we try to retrieve the memory. When you encode a memory, the hippocampus, a central part of the brain involved in memory function, takes a snapshot which is preserved in a set of neurons, says Kenneth Norman, a psychology professor at Princeton University. Those neurons can be activated later with a reminder or cue.

It is important to pay attention when you put down an item, or during encoding. If your state of mind at retrieval is different than it was during encoding, that could pose a problem. Case in point: You were starving when you walked into the house and deposited your keys. When you then go to look for them later, you’re no longer hungry so the memory may be harder to access.

The act of physically and mentally retracing your steps when looking for lost objects can work. Think back to your state of mind when you walked into the house (Were you hungry?). “The more you can make your brain at retrieval like the way it was when you lay down that original memory trace,” the more successful you will be, Dr. Norman says.

In a recent study, researchers in Germany found that the majority of people surveyed about forgetfulness and distraction had a variation in the so-called dopamine D2 receptor gene (DRD2), leading to a higher incidence of forgetfulness. According to the study, 75% of people carry a variation that makes them more prone to forgetfulness.

“Forgetfulness is quite common,” says Sebastian Markett, a researcher in psychology neuroscience at the University of Bonn in Germany and lead author of the study currently in the online version of the journal Neuroscience Letters, where it is expected to be published soon.

The study was based on a survey filled out by 500 people who were asked questions about memory lapses, perceptual failures (failing to notice a stop sign) and psychomotor failures (bumping into people on the street). The individuals also provided a saliva sample for molecular genetic testing.

About half of the total variation of forgetfulness can be explained by genetic effects, likely involving dozens of gene variations, Dr. Markett says.

The buildup of what psychologists call proactive interference helps explain how we can forget where we parked the car when we park in the same lot but different spaces every day. Memory may be impaired by the buildup of interference from previous experiences so it becomes harder to retrieve the specifics, like which parking space, Dr. Schacter says.

A study conducted by researchers at the Salk Institute for Biological Studies in California found that the brain keeps track of similar but distinct memories (where you parked your car today, for example) in the dentate gyrus, part of the hippocampus. There the brain stores separates recordings of each environment and different groups of neurons are activated when similar but nonidentical memories are encoded and later retrieved. The findings appeared last year in the online journal eLife.

The best way to remember where you put something may be the most obvious: Find a regular spot for it and somewhere that makes sense, experts say. If it’s reading glasses, leave them by the bedside. Charge your phone in the same place. Keep a container near the door for keys or a specific pocket in your purse.

Read the entire article here.

Image: Leather key chain. Courtesy of Wikipedia / The Egyptian.

 

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You Are Middle-Aged

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If you are losing touch with new technology, are growing increasingly hairy — in all the wrong places — and increasingly detest noisy environments, then you are middle-aged. Significantly, many now characterize the middle-aged years as 44-60. And, of course, if you continually misplace your glasses or feed the neighborhood birds more frequently, though you are still younger than 44 years, then you may just be acting middle-aged. Read on for some more telltale signs of your imminent demise.

From the Washington Post:

How do you know you’re middle-aged? How about when you wear clothes and shoes based on comfort rather than style, or grow hair in all the wrong places: nose, ears, eyebrows? Those are just two of the signs mentioned in a recent British survey about when middle age begins and how to identify it.

The 2,000 people surveyed by Benenden, a health-care and insurance firm, also made clear that middle age was no longer something for 30- or 40-year-olds to worry about. The life change, they said, began at 53. In fact, nearly half of the older-than-50s who were surveyed said they personally had not experienced “middle age” yet.

“A variety of factors — including more active lifestyles and healthier living — mean that people find their attitudes towards getting older are changing. Over half of the people surveyed didn’t feel that there even was such a thing as ‘middle age’ anymore,” Paul Keenan, head of communications at Benenden Health, said in a statement when the survey was released in August.

“Being ‘old’ appears to be a state of mind rather than being a specific age,” he added. “People no longer see ‘middle age’ as a numerical milestone and don’t tend to think of themselves as ‘old’ as they hit their fifties and beyond. I’m 54 myself, with the mind-set of a thirty-something — perhaps sometimes even that of a teenager!”

So beyond comfort shoes and ear hair, what are some signs that you’re no longer young? Here’s the full list offered up by respondents to the survey. Some are particularly British (e.g., joining the National Trust, taking a flask of tea on a day out). But you’ll get the point.

Losing touch with everyday technology such as tablets and TVs

Finding you have no idea what “young people” are talking about

Feeling stiff

Needing an afternoon nap

Groaning when you bend down

Not remembering the name of any modern bands

Talking a lot about your joints/ailments

Hating noisy pubs

Getting more hairy — ears, eyebrows, nose, face, etc.

Thinking policemen/teachers/doctors look really young

Preferring a night in with a board game than a night on the town

You don’t know any songs in the top 10

Choosing clothes and shoes for comfort rather than style

Taking a flask of tea on a day out

Obsessive gardening or bird feeding

Thinking there is nothing wrong with wearing an anorak

Forgetting people’s names

Booking a cruise

Misplacing your glasses, bag, car keys, etc.

Complaining about the rubbish on television these days

Gasping for a cup of tea

Getting bed socks for Christmas and being very grateful

Taking a keen interest in “The Antiques Road Show”

When you start complaining about more things

Listening to the Archers

You move from Radio 1 to Radio 2

Joining the National Trust

Being told off for politically incorrect opinions

Flogging the family car for something sportier

When you can’t lose six pounds in two days anymore

You get shocked by how racy music videos are

Taking a keen interest in the garden

Buying travel sweets for the car

Considering going on a “no children” cruise for a holiday

When you know your alcohol limit

Obsessively recycling/ knowing the collection dates

Always carrying a handy pack of tissues

Falling asleep after one glass of wine

Spending more money on face creams/anti-aging products

Preferring a Sunday walk to a lie-in

By comparison to those who participated in the British survey, Americans have a different take on when middle age begins, at least according to a paper published in 2011 by researchers at Florida State University. That study, which used nationally representative data collected in 1995-1996 and 2004-2006, showed that the perceived beginning of middle age varied, not surprisingly, depending on the age group that was providing the estimate. Overall, the researchers said, most people think of middle age as beginning at 44 and ending at 60.

Read the entire article here.

Image courtesy of Google Search.

 

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Chromosomal Chronometer

Researchers find possible evidence of DNA mechanism that keep track of age. It is too early to tell if changes over time in specific elements of our chromosomes result in or are a consequence of aging. Yet, this is a tantalizing discovery that bodes well for a better understanding into the genetic and biological systems that underlie the aging process.

From the Guardian:

A US scientist has discovered an internal body clock based on DNA that measures the biological age of our tissues and organs.

The clock shows that while many healthy tissues age at the same rate as the body as a whole, some of them age much faster or slower. The age of diseased organs varied hugely, with some many tens of years “older” than healthy tissue in the same person, according to the clock.

Researchers say that unravelling the mechanisms behind the clock will help them understand the ageing process and hopefully lead to drugs and other interventions that slow it down.

Therapies that counteract natural ageing are attracting huge interest from scientists because they target the single most important risk factor for scores of incurable diseases that strike in old age.

“Ultimately, it would be very exciting to develop therapy interventions to reset the clock and hopefully keep us young,” said Steve Horvath, professor of genetics and biostatistics at the University of California in Los Angeles.

Horvath looked at the DNA of nearly 8,000 samples of 51 different healthy and cancerous cells and tissues. Specifically, he looked at how methylation, a natural process that chemically modifies DNA, varied with age.

Horvath found that the methylation of 353 DNA markers varied consistently with age and could be used as a biological clock. The clock ticked fastest in the years up to around age 20, then slowed down to a steadier rate. Whether the DNA changes cause ageing or are caused by ageing is an unknown that scientists are now keen to work out.

“Does this relate to something that keeps track of age, or is a consequence of age? I really don’t know,” Horvath told the Guardian. “The development of grey hair is a marker of ageing, but nobody would say it causes ageing,” he said.

The clock has already revealed some intriguing results. Tests on healthy heart tissue showed that its biological age – how worn out it appears to be – was around nine years younger than expected. Female breast tissue aged faster than the rest of the body, on average appearing two years older.

Diseased tissues also aged at different rates, with cancers speeding up the clock by an average of 36 years. Some brain cancer tissues taken from children had a biological age of more than 80 years.

“Female breast tissue, even healthy tissue, seems to be older than other tissues of the human body. That’s interesting in the light that breast cancer is the most common cancer in women. Also, age is one of the primary risk factors of cancer, so these types of results could explain why cancer of the breast is so common,” Horvath said.

Healthy tissue surrounding a breast tumour was on average 12 years older than the rest of the woman’s body, the scientist’s tests revealed.

Writing in the journal Genome Biology, Horvath showed that the biological clock was reset to zero when cells plucked from an adult were reprogrammed back to a stem-cell-like state. The process for converting adult cells into stem cells, which can grow into any tissue in the body, won the Nobel prize in 2012 for Sir John Gurdon at Cambridge University and Shinya Yamanaka at Kyoto University.

“It provides a proof of concept that one can reset the clock,” said Horvath. The scientist now wants to run tests to see how neurodegenerative and infectious diseases affect, or are affected by, the biological clock.

Read the entire article here.

Image: Artist rendition of DNA fragment. Courtesy of Zoonar GmbH/Alamy.

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Living Long and Prospering on Ikaria

It’s safe to suggest that most of us above a certain age — let’s say 30 — wish to stay young. It is also safer to suggest, in the absence of a solution to this first wish, that many of us wish to age gracefully and happily. Yet for most of us, especially in the West, we age in a less dignified manner in combination with colorful medicines, lengthy tubes, and unpronounceable procedures. We are collectively living longer. But, the quality of those extra years leaves much to be desired.

In a quest to understand the process of aging more thoroughly researchers regularly descend on areas the world over that are known to have higher than average populations of healthy older people. These have become known as “Blue Zones”. One such place is a small, idyllic (there’s a clue right there) Greek island called Ikaria.

From the Guardian:

Gregoris Tsahas has smoked a packet of cigarettes every day for 70 years. High up in the hills of Ikaria, in his favourite cafe, he draws on what must be around his half-millionth fag. I tell him smoking is bad for the health and he gives me an indulgent smile, which suggests he’s heard the line before. He’s 100 years old and, aside from appendicitis, has never known a day of illness in his life.

Tsahas has short-cropped white hair, a robustly handsome face and a bone-crushing handshake. He says he drinks two glasses of red wine a day, but on closer interrogation he concedes that, like many other drinkers, he has underestimated his consumption by a couple of glasses.

The secret of a good marriage, he says, is never to return drunk to your wife. He’s been married for 60 years. “I’d like another wife,” he says. “Ideally one about 55.”

Tsahas is known at the cafe as a bit of a gossip and a joker. He goes there twice a day. It’s a 1km walk from his house over uneven, sloping terrain. That’s four hilly kilometres a day. Not many people half his age manage that far in Britain.

In Ikaria, a Greek island in the far east of the Mediterranean, about 30 miles from the Turkish coast, characters such as Gregoris Tsahas are not exceptional. With its beautiful coves, rocky cliffs, steep valleys and broken canopy of scrub and olive groves, Ikaria looks similar to any number of other Greek islands. But there is one vital difference: people here live much longer than the population on other islands and on the mainland. In fact, people here live on average 10 years longer than those in the rest of Europe and America – around one in three Ikarians lives into their 90s. Not only that, but they also have much lower rates of cancer and heart disease, suffer significantly less depression and dementia, maintain a sex life into old age and remain physically active deep into their 90s. What is the secret of Ikaria? What do its inhabitants know that the rest of us don’t?

The island is named after Icarus, the young man in Greek mythology who flew too close to the sun and plunged into the sea, according to legend, close to Ikaria. Thoughts of plunging into the sea are very much in my mind as the propeller plane from Athens comes in to land. There is a fierce wind blowing – the island is renowned for its wind – and the aircraft appears to stall as it turns to make its final descent, tipping this way and that until, at the last moment, the pilot takes off upwards and returns to Athens. Nor are there any ferries, owing to a strike. “They’re always on strike,” an Athenian back at the airport tells me.

Stranded in Athens for the night, I discover that a fellow thwarted passenger is Dan Buettner, author of a book called The Blue Zones, which details the five small areas in the world where the population outlive the American and western European average by around a decade: Okinawa in Japan, Sardinia, the Nicoya peninsula in Costa Rica, Loma Linda in California and Ikaria.

Tall and athletic, 52-year-old Buettner, who used to be a long-distance cyclist, looks a picture of well-preserved youth. He is a fellow with National Geographic magazine and became interested in longevity while researching Okinawa’s aged population. He tells me there are several other passengers on the plane who are interested in Ikaria’s exceptional demographics. “It would have been ironic, don’t you think,” he notes drily, “if a group of people looking for the secret of longevity crashed into the sea and died.”

Chatting to locals on the plane the following day, I learn that several have relations who are centenarians. One woman says her aunt is 111. The problem for demographers with such claims is that they are often very difficult to stand up. Going back to Methuselah, history is studded with exaggerations of age. In the last century, longevity became yet another battleground in the cold war. The Soviet authorities let it be known that people in the Caucasus were living deep into their hundreds. But subsequent studies have shown these claims lacked evidential foundation.

Since then, various societies and populations have reported advanced ageing, but few are able to supply convincing proof. “I don’t believe Korea or China,” Buettner says. “I don’t believe the Hunza Valley in Pakistan. None of those places has good birth certificates.”

However, Ikaria does. It has also been the subject of a number of scientific studies. Aside from the demographic surveys that Buettner helped organise, there was also the University of Athens’ Ikaria Study. One of its members, Dr Christina Chrysohoou, a cardiologist at the university’s medical school, found that the Ikarian diet featured a lot of beans and not much meat or refined sugar. The locals also feast on locally grown and wild greens, some of which contain 10 times more antioxidants than are found in red wine, as well as potatoes and goat’s milk.

Chrysohoou thinks the food is distinct from that eaten on other Greek islands with lower life expectancy. “Ikarians’ diet may have some differences from other islands’ diets,” she says. “The Ikarians drink a lot of herb tea and small quantities of coffee; daily calorie consumption is not high. Ikaria is still an isolated island, without tourists, which means that, especially in the villages in the north, where the highest longevity rates have been recorded, life is largely unaffected by the westernised way of living.”

But she also refers to research that suggests the Ikarian habit of taking afternoon naps may help extend life. One extensive study of Greek adults showed that regular napping reduced the risk of heart disease by almost 40%. What’s more, Chrysohoou’s preliminary studies revealed that 80% of Ikarian males between the ages of 65 and 100 were still having sex. And, of those, a quarter did so with “good duration” and “achievement”. “We found that most males between 65 and 88 reported sexual activity, but after the age of 90, very few continued to have sex.”

Read the entire article here.

Image: Agios Giorgis Beach, Ikaria. Courtesy of Island-Ikaria travel guide.

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Age is All in the Mind (Hypothalamus)

Researchers are continuing to make great progress in unraveling the complexities of aging. While some fingers point to the shortening of telomeres — end caps — in our chromosomal DNA as a contributing factor, other research points to the hypothalamus. This small sub-region of the brain has been found to play a major role in aging and death (though, at the moment only in mice).

From the New Scientist:

The brain’s mechanism for controlling ageing has been discovered – and manipulated to shorten and extend the lives of mice. Drugs to slow ageing could follow

Tick tock, tick tock… A mechanism that controls ageing, counting down to inevitable death, has been identified in the hypothalamus?– a part of the brain that controls most of the basic functions of life.

By manipulating this mechanism, researchers have both shortened and lengthened the lifespan of mice. The discovery reveals several new drug targets that, if not quite an elixir of youth, may at least delay the onset of age-related disease.

The hypothalamus is an almond-sized puppetmaster in the brain. “It has a global effect,” says Dongsheng Cai at the Albert Einstein College of Medicine in New York. Sitting on top of the brain stem, it is the interface between the brain and the rest of the body, and is involved in, among other things, controlling our automatic response to the world around us, our hormone levels, sleep-wake cycles, immunity and reproduction.

While investigating ageing processes in the brain, Cai and his colleagues noticed that ageing mice produce increasing levels of nuclear factor kB (NF-kB)? ?– a protein complex that plays a major role in regulating immune responses. NF-kB is barely active in the hypothalamus of 3 to 4-month-old mice but becomes very active in old mice, aged 22 to 24 months.

To see whether it was possible to affect ageing by manipulating levels of this protein complex, Cai’s team tested three groups of middle-aged mice. One group was given gene therapy that inhibits NF-kB, the second had gene therapy to activate NF-kB, while the third was left to age naturally.

This last group lived, as expected, between 600 and 1000 days. Mice with activated NF-kB all died within 900 days, while the animals with NF-kB inhibition lived for up to 1100 days.

Crucially, the mice that lived the longest not only increased their lifespan but also remained mentally and physically fit for longer. Six months after receiving gene therapy, all the mice were given a series of tests involving cognitive and physical ability.

In all of the tests, the mice that subsequently lived the longest outperformed the controls, while the short-lived mice performed the worst.

Post-mortem examinations of muscle and bone in the longest-living rodents also showed that they had many chemical and physical qualities of younger mice.

Further investigation revealed that NF-kB reduces the level of a chemical produced by the hypothalamus called gonadotropin-releasing hormone (GnRH) ?– better known for its involvement in the regulation of puberty and fertility, and the production of eggs and sperm.

To see if they could control lifespan using this hormone, the team gave another group of mice??– 20 to 24 months old??– daily subcutaneous injections of GnRH for five to eight weeks. These mice lived longer too, by a length of time similar to that of mice with inhibited NF-kB.

GnRH injections also resulted in new neurons in the brain. What’s more, when injected directly into the hypothalamus, GnRH influenced other brain regions, reversing widespread age-related decline and further supporting the idea that the hypothalamus could be a master controller for many ageing processes.

GnRH injections even delayed ageing in the mice that had been given gene therapy to activate NF-kB and would otherwise have aged more quickly than usual. None of the mice in the study showed serious side effects.

So could regular doses of GnRH keep death at bay? Cai hopes to find out how different doses affect lifespan, but says the hormone is unlikely to prolong life indefinitely since GnRH is only one of many factors at play. “Ageing is the most complicated biological process,” he says.

Read the entire article after the jump.

Image: Location of Hypothalamus. Courtesy of Colorado State University / Wikipedia.

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You Are Different From Yourself

The next time your spouse tells you that you’re “just not the same person anymore” there may be some truth to it. After all, we are not who we thought we would become, nor are we likely to become what we think. That’s the overall result of a recent study of human personality changes in around 20,000 people over time.

From Independent:

When we remember our past selves, they seem quite different. We know how much our personalities and tastes have changed over the years. But when we look ahead, somehow we expect ourselves to stay the same, a team of psychologists said Thursday, describing research they conducted of people’s self-perceptions.

They called this phenomenon the “end of history illusion,” in which people tend to “underestimate how much they will change in the future.” According to their research, which involved more than 19,000 people ages 18 to 68, the illusion persists from teenage years into retirement.

“Middle-aged people — like me — often look back on our teenage selves with some mixture of amusement and chagrin,” said one of the authors, Daniel T. Gilbert, a psychologist at Harvard. “What we never seem to realize is that our future selves will look back and think the very same thing about us. At every age we think we’re having the last laugh, and at every age we’re wrong.”

Other psychologists said they were intrigued by the findings, published Thursday in the journal Science, and were impressed with the amount of supporting evidence. Participants were asked about their personality traits and preferences — their favorite foods, vacations, hobbies and bands — in years past and present, and then asked to make predictions for the future. Not surprisingly, the younger people in the study reported more change in the previous decade than did the older respondents.

But when asked to predict what their personalities and tastes would be like in 10 years, people of all ages consistently played down the potential changes ahead.

Thus, the typical 20-year-old woman’s predictions for her next decade were not nearly as radical as the typical 30-year-old woman’s recollection of how much she had changed in her 20s. This sort of discrepancy persisted among respondents all the way into their 60s.

And the discrepancy did not seem to be because of faulty memories, because the personality changes recalled by people jibed quite well with independent research charting how personality traits shift with age. People seemed to be much better at recalling their former selves than at imagining how much they would change in the future.

Why? Dr. Gilbert and his collaborators, Jordi Quoidbach of Harvard and Timothy D. Wilson of the University of Virginia, had a few theories, starting with the well-documented tendency of people to overestimate their own wonderfulness.

“Believing that we just reached the peak of our personal evolution makes us feel good,” Dr. Quoidbach said. “The ‘I wish that I knew then what I know now’ experience might give us a sense of satisfaction and meaning, whereas realizing how transient our preferences and values are might lead us to doubt every decision and generate anxiety.”

Or maybe the explanation has more to do with mental energy: predicting the future requires more work than simply recalling the past. “People may confuse the difficulty of imagining personal change with the unlikelihood of change itself,” the authors wrote in Science.

The phenomenon does have its downsides, the authors said. For instance, people make decisions in their youth — about getting a tattoo, say, or a choice of spouse — that they sometimes come to regret.

And that illusion of stability could lead to dubious financial expectations, as the researchers showed in an experiment asking people how much they would pay to see their favorite bands.

When asked about their favorite band from a decade ago, respondents were typically willing to shell out $80 to attend a concert of the band today. But when they were asked about their current favorite band and how much they would be willing to spend to see the band’s concert in 10 years, the price went up to $129. Even though they realized that favorites from a decade ago like Creed or the Dixie Chicks have lost some of their luster, they apparently expect Coldplay and Rihanna to blaze on forever.

“The end-of-history effect may represent a failure in personal imagination,” said Dan P. McAdams, a psychologist at Northwestern who has done separate research into the stories people construct about their past and future lives. He has often heard people tell complex, dynamic stories about the past but then make vague, prosaic projections of a future in which things stay pretty much the same.

Read the entire article after the jump.

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So You Wanna Be a Rockstar?

Many of us harbor dreams, often secret ones, of becoming a famous rockstar. Well, if you want to live well passed middle age, think again. Being a rockstar and living a long life are not statistically compatible, especially if you’re American. You choose.

From ars technica:

Hedonism. Substance abuse. Risky behavior. Rock stars from Elvis Presley to Amy Winehouse have ended up famous not only for their music but for the decadent lifestyle it enabled, one that eventually contributed to their deaths. But how much does the rock lifestyle really hurt?

Quite a bit. That’s the conclusion of a new study that tracked nearly 1,500 chart-topping musicians and found that their life expectancy after fame really was lower than that of the general population. North American solo musicians seem to have it especially bad.

This wasn’t necessarily what you’d expect. A huge number of studies have shown that wealth is generally associated with greater longevity, possibly as a result of better health care, better diet, and lower stress. Not only are rock musicians dying faster than the general populace, but they’re completely negating the impact of any wealth that their fame brought to them.

To get a collection of rock stars for their study, the authors combed the charts and took advantage of a large poll that listed the top 1,000 albums of all time. Altogether, their subjects reached fame between the years of 1956 and 2006 and included everyone from Elvis Presley to Regina Spektor to the Arctic Monkeys. From there, the authors searched the news and Wikipedia, looking for reports of death. With that information in hand, they compared the artists’ life expectancies to those of the general population.

Only about two-thirds of North American stars were still alive 40 years after their first brush with fame, compared with about 80 percent of a matched population—and there was never a point at which they outlived their non-famous peers. Typically, Europeans have greater life expectancies, but European stars did not, tracking the longevity of average North Americans for the first few decades.

Oddly, however, once they survived 20 years after hitting the big time, European rock stars started to do better, outliving the typical North American. And, by 35 years, they caught up with the average European’s life expectancy. (No word from the authors on whether this trend would stay the same if the analysis excluded the members of the Rolling Stones.) On both continents, solo performers did worse than members of a band.

So what’s killing the famous? The authors identified cause of death wherever possible and classified it as either “other” or “substance use or risk-related deaths.” The latter category included “drug or alcohol-related chronic disorder, overdose or accident, and other risk-related causes that may or may not have been related to substance use, i.e., suicide and violence.” They also tried to determine (using biographical data) whether any of the deceased stars had suffered adverse childhood experiences, such as a substance abusing or a mentally ill parent.

Of those without any obvious childhood issues, under a third died of substance abuse or other risky behavior. Adding a single adverse childhood influence raised that rate to 42 percent. Two or more adverse events, and the rate shot up to about 80 percent.

These same sorts of childhood problems tend to lead to substance abuse and other troubles in the general population as well, and the authors conclude that the hedonism we associate with rock stars is less a lifestyle choice and more an outcome of early life issues.

Read the entire article after the jump.

Image: Spinal Tap backstage at CBGB’s in New York City. Photograph: Ebet Roberts/Redferns / Guardian.

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Telomere Test: A Date With Death

In 1977 Elizabeth Blackburn and Joseph Gall, molecular biologists, discovered the structure of the end caps, known as telomeres, of chromosomes. In 2009, Blackburn and colleagues Carol Greider and Jack Szostak shared the Nobel prize in Physiology or Medicine for discovering the enzyme telomerase, the enzyme responsible for replenishing telomeres.

It turns out that telomeres are rather important. Studies shows that telomeres regulate cell division, and as a consequence directly influence aging and life span. When a cell divides the length of its chromosomal telomeres shortens. Once a telomere is depleted its chromosome, and DNA, can no longer be replicated accurately, and the cell no longer divides, hastening cell death.

From the Independent:

A blood test to determine how fast someone is ageing has been shown to work on a population of wild birds, the first time the ageing test has been used successfully on animals living outside a laboratory setting.

The test measures the average length of tiny structures on the tips of chromosomes called telomeres which are known to get shorter each time a cell divides during an organism’s lifetime.

Telomeres are believed to act like internal clocks by providing a more accurate estimate of a person’s true biological age rather than their actual chronological age.

This has led some experts to suggest that telomere tests could be used to estimate not only how fast someone is ageing, but possibly how long they have left to live if they die of natural causes.

Telomere tests have been widely used on experimental animals and at least one company is offering a £400 blood test in the UK for people interested in seeing how fast they are ageing based on their average telomere length.

Now scientists have performed telomere tests on an isolated population of songbirds living on an island in the Seychelles and found that the test does indeed accurately predict an animal’s likely lifespan.

“We saw that telomere length is a better indicator of life expectancy than chronological age. So by measuring telomere length we have a way of estimating the biological age of an individual – how much of its life it has used up,” said David Richardson of the University of East Anglia.

The researchers tested the average telomere lengths of a population of 320 Seychelles Warblers living on the remote Cousin Island, which ornithologists have studied for 20 years, documenting the life history of each bird.

“Our results provide the first clear and unambiguous evidence of a relationship between telomere length and mortality in the wild, and substantiate the prediction that telomere length and shortening rate can act as an indicator of biological age further to chronological age,” says the study published in the journal Molecular Ecology.

Studying an island population of wild birds was important because there were no natural predators and little migration, meaning that the scientists could accurately study the link between telomere length and a bird’s natural lifespan.

“We wanted to understand what happens over an entire lifetime, so the Seychelles warbler is an ideal research subject. They are naturally confined to an isolated tropical island, without any predators, so we can follow individuals throughout their lives, right into old age,” Dr Richardson said.

“We investigated whether, at any given age, their telomere lengths could predict imminent death. We found that short and rapidly shortening telomeres were a good indication that the bird would die within a year,” he said.

Read the entire article following the jump.

Infographic courtesy of Independent.

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Letting Go of Regrets

From Mind Matters over at Scientific American:

The poem “Maud Muller” by John Greenleaf Whittier aptly ends with the line, “For of all sad words of tongue or pen, The saddest are these: ‘It might have been!’” What if you had gone for the risky investment that you later found out made someone else rich, or if you had had the guts to ask that certain someone to marry you? Certainly, we’ve all had instances in our lives where hindsight makes us regret not sticking our neck out a bit more.

But new research suggests that when we are older these kinds of ‘if only!’ thoughts about the choices we made may not be so good for our mental health. One of the most important determinants of our emotional well being in our golden years might be whether we learn to stop worrying about what might have been.

In a new paper published in Science, researchers from the University Medical Center Hamburg-Eppendorf in Hamburg, Germany, report evidence from two experiments which suggest that one key to aging well might involve learning to let go of regrets about missed opportunities. Stafanie Brassen and her colleagues looked at how healthy young participants (mean age: 25.4 years), healthy older participants (65.8 years), and older participants who had developed depression for the first time later in life (65.6 years) dealt with regret, and found that the young and older depressed patients seemed to hold on to regrets about missed opportunities while the healthy older participants seemed to let them go.

To measure regret over missed opportunities, the researchers adapted an established risk taking task into a clever game in which the participants looked at eight wooden boxes lined up in a row on a computer screen and could choose to reveal the contents of the boxes one at a time, from left to right. Seven of the boxes had gold in them, which the participants would earn if they chose to open them. One box, however, had a devil in it. What happens if they open the box with the devil in it? They lose that round and any gold they earned so far with it.

Importantly, the participants could choose to cash out early and keep any gold they earned up to that point. Doing this would reveal the location of the devil and coincidently all of the gold they missed out on. Sometimes this wouldn’t be a big deal, because the devil would be in the next box. No harm, no foul.  But sometimes the devil might be several boxes away. In this case, you might have missed out on a lot of potential earnings, and this had the potential to induce feelings of regret.

In their first experiment, Brassen and colleagues had all of the participants play this ‘devil game’ during a functional magnetic resonance (fMRI) brain scan.  They wanted to test whether young participants, older depressed, and healthy older participants responded differently to missed opportunities during the game, and whether these differences might also be reflected in activity in one area of the brain called the ventral striatum (an area known to very active when we experience regret) and another area of the brain called the anterior cingulate (an area known to be active when controlling our emotions).

Brassen and her colleagues found that for healthy older participants, the area of the brain which is usually active during the experience of regret, the ventral striatum, was much less active during rounds of the game where they missed out on a lot of money, suggesting that the healthily aging brains were not processing regret in the same way the young and depressed older brains were. Also, when they looked at the emotion controlling center of the brain, the anterior cingulate, the researchers found that this area was much more active in the healthy older participants than the other two groups. Interestingly, Brassen and her colleagues found that the bigger the missed opportunity, the greater the activity in this area for healthy older participants, which suggests that their brains were actively mitigating their experience of regret.

Read the entire article after the jump.

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The Evolutionary Benefits of Middle Age

David Bainbridge, author of “Middle Age: A Natural History”, examines the benefits of middle age. Yes, really. For those of us in “middle age” it’s not surprising to see that this period is not limited to decline, disease and senility. Rather, it’s a pre-programmed redistribution of physical and mental resources designed to cope with our ever-increasing life spans.

From David Bainbridge over at New Scientist:

As a 42-year-old man born in England, I can expect to live for about another 38 years. In other words, I can no longer claim to be young. I am, without doubt, middle-aged.

To some people that is a depressing realization. We are used to dismissing our fifth and sixth decades as a negative chapter in our lives, perhaps even a cause for crisis. But recent scientific findings have shown just how important middle age is for every one of us, and how crucial it has been to the success of our species. Middle age is not just about wrinkles and worry. It is not about getting old. It is an ancient, pivotal episode in the human life span, preprogrammed into us by natural selection, an exceptional characteristic of an exceptional species.

Compared with other animals, humans have a very unusual pattern to our lives. We take a very long time to grow up, we are long-lived, and most of us stop reproducing halfway through our life span. A few other species have some elements of this pattern, but only humans have distorted the course of their lives in such a dramatic way. Most of that distortion is caused by the evolution of middle age, which adds two decades that most other animals simply do not get.

An important clue that middle age isn’t just the start of a downward spiral is that it does not bear the hallmarks of general, passive decline. Most body systems deteriorate very little during this stage of life. Those that do, deteriorate in ways that are very distinctive, are rarely seen in other species and are often abrupt.

For example, our ability to focus on nearby objects declines in a predictable way: Farsightedness is rare at 35 but universal at 50. Skin elasticity also decreases reliably and often surprisingly abruptly in early middle age. Patterns of fat deposition change in predictable, stereotyped ways. Other systems, notably cognition, barely change.

Each of these changes can be explained in evolutionary terms. In general, it makes sense to invest in the repair and maintenance only of body systems that deliver an immediate fitness benefit — that is, those that help to propagate your genes. As people get older, they no longer need spectacular visual acuity or mate-attracting, unblemished skin. Yet they do need their brains, and that is why we still invest heavily in them during middle age.

As for fat — that wonderfully efficient energy store that saved the lives of many of our hard-pressed ancestors — its role changes when we are no longer gearing up to produce offspring, especially in women. As the years pass, less fat is stored in depots ready to meet the demands of reproduction — the breasts, hips and thighs — or under the skin, where it gives a smooth, youthful appearance. Once our babymaking days are over, fat is stored in larger quantities and also stored more centrally, where it is easiest to carry about. That way, if times get tough we can use it for our own survival, thus freeing up food for our younger relatives.

Read the entire article after the jump.

Image: Middle Age Couple Laughing. Courtesy of Cindi Matthews / Flickr.

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When Will I Die?

Would you like to know when you will die?

This is a fundamentally personal and moral question which many may prefer to keep unanswered.  That said, while scientific understanding of aging is making great strides it cannot yet provide an answer to the question. Though it may only be a matter of time.

Giles Tremlett over at the Guardian gives us a personal account of the fascinating science of telomeres, the end-caps on our chromosomes, and why they potentially hold a key to that most fateful question.

From the Guardian:

As a taxi takes me across Madrid to the laboratories of Spain’s National Cancer Research Centre, I am fretting about the future. I am one of the first people in the world to provide a blood sample for a new test, which has been variously described as a predictor of how long I will live, a waste of time or a handy indicator of how well (or badly) my body is ageing. Today I get the results.

Some newspapers, to the dismay of the scientists involved, have gleefully announced that the test – which measures the telomeres (the protective caps on the ends of my chromosomes) – can predict when I will die. Am I about to find out that, at least statistically, my days are numbered? And, if so, might new telomere research suggesting we can turn back the hands of the body’s clock and make ourselves “biologically younger” come to my rescue?

The test is based on the idea that biological ageing grinds at your telomeres. And, although time ticks by uniformly, our bodies age at different rates. Genes, environment and our own personal habits all play a part in that process. A peek at your telomeres is an indicator of how you are doing. Essentially, they tell you whether you have become biologically younger or older than other people born at around the same time.

The key measure, explains María Blasco, a 45-year-old molecular biologist, head of Spain’s cancer research centre and one of the world’s leading telomere researchers, is the number of short telomeres. Blasco, who is also one of the co-founders of the Life Length company which is offering the tests, says that short telomeres do not just provide evidence of ageing. They also cause it. Often compared to the plastic caps on a shoelace, there is a critical level at which the fraying becomes irreversible and triggers cell death. “Short telomeres are causal of disease because when they are below a [certain] length they are damaging for the cells. The stem cells of our tissues do not regenerate and then we have ageing of the tissues,” she explains. That, in a cellular nutshell, is how ageing works. Eventually, so many of our telomeres are short that some key part of our body may stop working.

The research is still in its early days but extreme stress, for example, has been linked to telomere shortening. I think back to a recent working day that took in three countries, three news stories, two international flights, a public lecture and very little sleep. Reasonable behaviour, perhaps, for someone in their 30s – but I am closer to my 50s. Do days like that shorten my expected, or real, life-span?

Read more of this article here.

Image: chromosomes capped by telomeres (white), courtesy of Wikipedia.

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The Arrow of Time

No, not a cosmologist’s convoluted hypothesis as to why time moves in only (so far discovered) one direction. The arrow of time here is a thoroughly personal look at the linearity of the 4th dimension and an homage to the family portrait in the process.

The family takes a “snapshot” of each member at the same time each year; we’ve just glimpsed the latest for 2011. And, in so doing they give us much to ponder on the nature of change and the nature of stasis.

From Diego Goldberg and family:

Catch all the intervening years between 1976 and 2011 at theSource here.

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Unlocking the Secrets of Longevity Genes

From Scientific American:

A handful of genes that control the body’s defenses during hard times can also dramatically improve health and prolong life in diverse organisms. Understanding how they work may reveal the keys to extending human life span while banishing diseases of old age.

You can assume quite a bit about the state of a used car just from its mileage and model year. The wear and tear of heavy driving and the passage of time will have taken an inevitable toll. The same appears to be true of aging in people, but the analogy is flawed because of a crucial difference between inanimate machines and living creatures: deterioration is not inexorable in biological systems, which can respond to their environments and use their own energy to defend and repair themselves.

At one time, scientists believed aging to be not just deterioration but an active continuation of an organism’s genetically programmed development. Once an individual achieved maturity, “aging genes” began to direct its progress toward the grave. This idea has been discredited, and conventional wisdom now holds that aging really is just wearing out over time because the body’s normal maintenance and repair mechanisms simply wane. Evolutionary natural selection, the logic goes, has no reason to keep them working once an organism has passed its reproductive age.

More from theSource here.

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