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Jun 3, 2013

Lust for life: breaking the 120-year barrier in human ageing

Posted by in categories: biological, biotech/medical, life extension

By Avi Roy, University of Buckingham

In rich countries, more than 80% of the population today will survive past the age of 70. About 150 years ago, only 20% did. In all this while, though, only one person lived beyond the age of 120. This has led experts to believe that there may be a limit to how long humans can live.

Animals display an astounding variety of maximum lifespan ranging from mayflies and gastrotrichs, which live for 2 to 3 days, to giant tortoises and bowhead whales, which can live to 200 years. The record for the longest living animal belongs to the quahog clam, which can live for more than 400 years.

If we look beyond the animal kingdom, among plants the giant sequoia lives past 3000 years, and bristlecone pines reach 5000 years. The record for the longest living plant belongs to the Mediterranean tapeweed, which has been found in a flourishing colony estimated at 100,000 years old.

This jellyfish never dies. Michael W. May

Some animals like the hydra and a species of jellyfish may have found ways to cheat death, but further research is needed to validate this.

The natural laws of physics may dictate that most things must die. But that does not mean we cannot use nature’s templates to extend healthy human lifespan beyond 120 years.

Putting a lid on the can

Gerontologist Leonard Hayflick at the University of California thinks that humans have a definite expiry date. In 1961, he showed that human skin cells grown under laboratory conditions tend to divide approximately 50 times before becoming senescent, which means no longer able to divide. This phenomenon that any cell can multiply only a limited number of times is called the Hayflick limit.

Since then, Hayflick and others have successfully documented the Hayflick limits of cells from animals with varied life spans, including the long-lived Galapagos turtle (200 years) and the relatively short-lived laboratory mouse (3 years). The cells of a Galapagos turtle divide approximately 110 times before senescing, whereas mice cells become senescent within 15 divisions.

The Hayflick limit gained more support when Elizabeth Blackburn and colleagues discovered the ticking clock of the cell in the form of telomeres. Telomeres are repetitive DNA sequence at the end of chromosomes which protects the chromosomes from degrading. With every cell division, it seemed these telomeres get shorter. The result of each shortening was that these cells were more likely to become senescent.

Other scientists used census data and complex modelling methods to come to the same conclusion: that maximum human lifespan may be around 120 years. But no one has yet determined whether we can change the human Hayflick limit to become more like long-lived organisms such as the bowhead whales or the giant tortoise.

What gives more hope is that no one has actually proved that the Hayflick limit actually limits the lifespan of an organism. Correlation is not causation. For instance, despite having a very small Hayflick limit, mouse cells typically divide indefinitely when grown in standard laboratory conditions. They behave as if they have no Hayflick limit at all when grown in the concentration of oxygen that they experience in the living animal (3–5% versus 20%). They make enough telomerase, an enzyme that replaces degraded telomeres with new ones. So it might be that currently the Hayflick “limit” is more a the Hayflick “clock”, giving readout of the age of the cell rather than driving the cell to death.

The trouble with limits

Happy last few days? It doesn’t have to end this way. ptimat

The Hayflick limit may represent an organism’s maximal lifespan, but what is it that actually kills us in the end? To test the Hayflick limit’s ability to predict our mortality we can take cell samples from young and old people and grow them in the lab. If the Hayflick limit is the culprit, a 60-year-old person’s cells should divide far fewer times than a 20-year-old’s cells.

But this experiment fails time after time. The 60-year-old’s skin cells still divide approximately 50 times – just as many as the young person’s cells. But what about the telomeres: aren’t they the inbuilt biological clock? Well, it’s complicated.

When cells are grown in a lab their telomeres do indeed shorten with every cell division and can be used to find the cell’s “expiry date”. Unfortunately, this does not seem to relate to actual health of the cells.

It is true that as we get older our telomeres shorten, but only for certain cells and only during certain time. Most importantly, trusty lab mice have telomeres that are five times longer than ours but their lives are 40 times shorter. That is why the relationship between telomere length and lifespan is unclear.

Apparently using the Hayflick limit and telomere length to judge maximum human lifespan is akin to understanding the demise of the Roman empire by studying the material properties of the Colosseum. Rome did not fall because the Colosseum degraded; quite the opposite in fact, the Colosseum degraded because the Roman Empire fell.

Within the human body, most cells do not simply senesce. They are repaired, cleaned or replaced by stem cells. Your skin degrades as you age because your body cannot carry out its normal functions of repair and regeneration.

To infinity and beyond

If we could maintain our body’s ability to repair and regenerate itself, could we substantially increase our lifespans? This question is, unfortunately, vastly under-researched for us to be able to answer confidently. Most institutes on ageing promote research that delays onset of the diseases of ageing and not research that targets human life extension.

Those that look at extension study how diets like calorie restriction affect human health or the health impacts of molecules like resveratrol derived from red wine. Other research tries to understand the mechanisms underlying the beneficial effects of certain diets and foods with hopes of synthesising drugs that do the same. The tacit understanding in the field of gerontology seems to be that, if we can keep a person healthy longer, we may be able to modestly improve lifespan.

Living long and having good health are not mutually exclusive. On the contrary, you cannot have a long life without good health. Currently most ageing research is concentrated on improving “health”, not lifespan. If we are going to live substantially longer, we need to engineer our way out of the current 120-year-barrier.

Avi Roy does not work for, consult to, own shares in or receive funding from any company or organisation that would benefit from this article, and has no relevant affiliations.

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  1. Greg Fahy says:

    For more perspective and a roadmap of some of the anticipated advances that will ultimately extend human lifespan perhaps indefinitely, see “The Future of Aging: Pathways to Human Life Extension” (Springer, 2010). The Hayflick has been overcome in cultured cells, which go on to divide indefinitely without losing their normal phenotypes.

  2. And then there’s also that ol’ chestnut question — ‘should we?’. In the 5th edition of the Death and Anti-Death Anthology I asked the question ‘Do humans have a right NOT to die?’

    We’re getting far better at extending a human’s ability to live longer however that does not also extend to life issues so that we now have healthier shells with degraded brain capabilities leading to ever increasing costs associated with health care.

    And by and large people forget that ALL technology resides in a social setting. Ultimately society decides the benefits or otherwise of technology — would keeping people alive longer whilst others struggle to survive be deemed appropriate? Should we aim to extend the life of ‘us’ whilst failing to address the waste problem and environmental degradation that our behaviours have thus far, wrought?

    Would increasing the living age actually pose an existential threat to the species? If our behaviours are anything to go by, it is not too far a stretch to suggest that rather than assist the species, longer living people might accelerate its demise due to an unwillingness to address our resource use. We’ll simply starve and poison ourselves to death far quicker, perhaps?
    Marcus Barber

  3. PirateRo says:

    It is always the same with these things. Death, as a process may make sense at the bottom of a gravity well but in the sense of a universe, less so. Engineering our evolution will remove this limitation and it will continue the conversation we have all been having for the past 2M years into the future where we can explore new realms and advance our species and maybe find a friend or two to pal around with.

    Death is too inconvenient and makes for much to drastic a loss. Time for it to go.

  4. Greg Fahy says:

    Read Sonia Arrison’s book for a debunking of Marcus type arguments.