Biomedicine

The Genetic Secrets of Longevity

A study of long-lived families will help isolate the genetic mysteries that allow some people to live disease-free into their nineties and beyond.

  • Monday, July 24, 2006
  • By Emily Singer

Thomas Perls has definitive proof that both mind and body can escape the decay of time. He's seen firsthand the brain of a deceased 100-year-old woman that showed no signs of the neurological wear-and-tear that usually accumulates in the aging brain. Not a hint, for example, of the plaques and tangles that accompany normal aging and are a hallmark of Alzheimer's disease. What's more, before her death, the donor had the cognitive abilities of a 60-year-old.

In 2005, Maria Esther Capovilla of Ecuador was confirmed as the oldest living person by Guinness World Records. At 116, she was still reading and walking without a cane. Researchers hope to understand how people like Capovilla live so long and remain so healthy. (Credit: Reuters)

As director of the New England Centenarian Study at Boston Medical Center, Perls has spent the last decade hunting for genetic and environmental clues to these ageless wonders. He hopes studies of very long-lived people will explain why some individuals succumb to diabetes, heart disease, or Alzheimer's at a relatively young age, while others live two decades beyond the average life expectancy and show remarkably few signs of the passage of time. (The extraordinary brain described above was donated by a participant in the study.)

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Perls' study, made up of 800 centenarians, is the largest ever conducted of people who have lived to the age of 100 and beyond. Not only do these people live long, but many of them seem to escape the disability associated with diseases of aging or to compress that disability period into a short time span very late in life.

While researchers haven't yet found the source of centenarians' enviable passage into old age, they have published numerous studies showing that longevity runs in families.

Perls' team is now starting a new, larger study of long-lived families, which he hopes will bring better insight into the specific genetic and environmental factors that underlie longevity. His center will conduct one arm of the Long Life Family Study, funded by the National Institute on Aging, in which scientists at four different sites will recruit 1,000 families that show exceptional longevity. Eventually he hopes to be able to translate the findings from these families into broadly usable treatments for the diseases of aging.

Here Perls tells Technology Review what he's learned so far about aging -- and what he hopes to uncover.

Technology Review: What makes centenarians so interesting from a medical perspective?

Thomas Perls: These individuals have a remarkable potential for resilience. Forty percent of centenarians have diseases they've been living with 20 years, but they don't show disability from these diseases until their early-to-mid-nineties. What is this resilience that allows people to live with these diseases and not have problems until the relative end of their extremely long lives?

In addition, 13 percent of centenarians seem to escape the diseases of aging altogether. Some even do this despite some horrendous health habits. We want to figure out how to translate that into strategies for other people. Our goal is to get people to markedly delay or escape disability associated with aging. If we could do that, it would be a huge boon to the health system and our society.

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Guest (Harvey S. Frey MD)

  • 2032 Days Ago
  • 07/24/2006

Longevity research

So is Pontin going to offer a prize to anyone who can demonstrate that this research isn't worth even discussing?

Reply

Guest (Jason Pontin)

  • 2032 Days Ago
  • 07/24/2006

Not So

On no occasion have I attacked legitimate anti-aging science as being, in principle, wrong. We are very interested in the potential of anti-aging science to compress morbidity, or even extend human lifespans. I was dubious that SENS was good science; and I remain convinced that its timelines are highly unlikely.

Reply

Guest (Robert Bradbury)

  • 2029 Days Ago
  • 07/27/2006

A non-aging genome

TR should ask better questions. If we can disassemble the human genome in less than 10 years for less than $3 billion why can't we assemble a non-aging human genome for similar amounts?

After all, are we not spending 10x that amount each year ($30+ billion in BigPharama R&D) to addict people to more drugs that fail to cure the fundamental problems (genome defects)?

A scientist might tell you that first you have to understand everything about a problem before you can fix it.  An engineer will simply solve the problem -- even if they don't fully understand how they did so.

Reply

Guest (Robert Young)

  • 2029 Days Ago
  • 07/27/2006

Let's be honest, no one has given the NECS $3billion for this study...I'm sure a lot more could be done with that kind of money.

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Guest

  • 2031 Days Ago
  • 07/25/2006

Ha! Well, by using deduction instead of induction, one is always more safe, but often, more conservative. SENS is right on. Without creativity we would know nothing of the structure of DNA, or other important biological functions. We must begin, or at least incorporate, SENS studies, Calore Restriction  studies, and so on.

Reply

Guest (Martin Cohen)

  • 2032 Days Ago
  • 07/24/2006

Not original

Sounds like Heinlein's "Methuselah's Children". Approximate quote: "The best way to live a long time is to have grandparents who lived a long time."

See http://www.amazon.com/gp/product/0671577808/ref=cm_lm_byauthor_prod_9_0/103-8561885-8282224?%5Fencoding=UTF8&v=glance&n=283155

(sorry about the long url)

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Guest (Robert Young)

  • 2032 Days Ago
  • 07/24/2006

Not Original

Yes, the boring, mundane world of proving 'everyday truths' like 'longevity is related to genetics'.  It's not exciting like science fiction, is it?

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Guest (Expert)

  • 2030 Days Ago
  • 07/26/2006

Not original

Yes, it is well known to scientists since 1930s that longevity runs in families.
See for example numerous scientific publications by Raymond Pearl on this very subject, including his famous books.
Not sure what is new here.

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Guest (Methuselah )

  • 2031 Days Ago
  • 07/25/2006

What will my long life allow me to see and do?

I tried Perl's life expectancy calculator and found I'm good for another 38 years - not bad for someone who just turned 60. So I guess I should get out the topographical maps and start charting where the new ocean front property is going to be once Antarctica and Greenland melt. And I better find a place where I can walk where I want to go because we're running out of oil. And at a high latitude so the temperature is bearable.
Considering all the ill effects of FDA-approved drugs, I better continue to not take any prescription drugs. And stay away from politically hot spots so I don't become an innocent bystander.
Sorry guys, when you  are preordained to live so long, you tend to focus on some of the other problems we don't seem to be able to get around to finding solutions for....

Reply

Guest (RK Murthy)

  • 2018 Days Ago
  • 08/07/2006

What will my long life allow me to see and do?

I agree, Methuselah, I agree. Just live along! You are destined to love so, live along! I always remember J Krishnamurti's teachings, that by "negation you reach positive".  If you have to clean a surface, what you do is to remove (negate) the dirt from that surface.  What remains is a clean surface!  You had not been doing anything else except removing dirt!  Similarly if you do not add up dirt in the ingredients of daily life concerning you, your life goes on!

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Guest (Brett Bennett)

  • 2031 Days Ago
  • 07/25/2006

Calorie Restriction

Obviously this research has grave errors, especially in regards to the study's leader's perspective on calorie restriction. By looking at the longest lived people across the world, usually eating a western based diet, the diet only considers people on a 'traditional' diet, which does not tell whether or not calorie restriction is important or not. Merely looking at the genetics of old people is fine--it tells us much--but if the base, i.e. the diet, is not ideal, the only thing gained by the study is the genetic characteristics of older people, which is important indeed, but it seems to lack in sophistication. But, the author does not categorically deny CR or any diet, and so he can be let off the hook slightly.

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Guest (Robert Young)

  • 2029 Days Ago
  • 07/27/2006

We are not 'on your hook' or beholden to your 'CR agenda.'  Also, you misinterpet much...we are finding that many of the supercentenarians do in fact practice reduced-portion diets, if not your definition of severe caloric restriction.  Would you please stop the 'friendly-fire' and discuss these matters through private dialogue first?

Reply

Guest (Curious)

  • 2029 Days Ago
  • 07/27/2006

Please elaborate

Brett Bennett wrote:

"Obviously this research has grave errors..."

Could you please elaborate more on this topic?

Reply

Guest (Robert Bradbury)

  • 2029 Days Ago
  • 07/27/2006

Disease predisposition vs. longevity genes

The problem is that the lack of disease predisposition genes does not equal extended longevity.  Long lived people such as centenarians and supercentenarians could simply have hit the genetic lottery.  All one will discover in such studies is that they lack the gene variants which predispose them to specific diseases.  Because of the large numbers of genes involved large numbers of individuals will be required to clearly prove this.  That is one of the major reasons that Aeiveos Sciences Group discontinued its Centenarian genotyping project in 1997.

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