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Science: The Myth of Extreme Longevity

Science: The Myth of Extreme Longevity

Aging is inevitable. This, in short, is the conclusion Dr Robin Holliday reached after spending his career researching genetics, cell biology, and aging. In the following article Holliday will explain why we will never be able to live forever.

There are two reasons for believing that the predictions of the anti- aging movement are incorrect. First, it is claimed that major age-associated diseases will be eliminated. These include cardiovascular disease, cancer, dementia, and late onset diabetes. At present there is research worldwide on the causes and treatment of these and also many other age-associated health problems. Yet anti-aging advocates claim that they can do better than all these biomedical laboratories put together. Is this realistic? Second, the proponents of anti-aging research seem to have limited knowledge of aging itself. Aging is built into the evolved anatomy and physiology of every animal. Moreover, aging has multiple causes and  is a very complex process, during which changes have been documented in molecules, cells, tissues, and organs. Which raises the question: How could all of these be reversed or bypassed? (see ref.1)

It is important to understand why aging is ubiquitous in animals. In a natural environment, most adult animals die fairly young from predation, starvation, disease or drought,  so most offspring are produced by young adults. It is advantageous to invest resources in reproduction rather than in the preservation of the adult body, because this is unlikely to survive very long. It can be shown that a population of animals that age has greater Darwinian fitness than one which is potentially immortal.

In the twentieth century most research on aging was descriptive, which revealed its complexity.  There was little agreement about the fundamental causes of aging, and many different theories were proposed. At the end of the twentieth century  it was realized that there were many different causes of aging, not just one or a few.  The reasons for aging became apparent, and books were published (refs 2-4) with positive titles: How and Why We Age by Leonard Hayflick (1994 and 1996);  Why We Age by Steve Austad (1996), and Understanding Ageing by myself (1995). It  became apparent that the evolved design of many animals made aging inevitable, and also that an animal that could survive indefinitely would have a very different design.

Aging and molecular disorder

Here I am referring mainly to mammalian aging, and summarise the changes that have been well documented. The structure and function of the heart and major blood vessels deteriorate with aging. The brain accumulates cellular and extracellular defects, and neurons are lost. The lens and retina of the eye are subject to changes that impair normal sight, and deafness is a common problem. The normal structure and functions of kidneys is often not maintained. The incidence of many carcinomas is strongly age-associated. The connective tissue protein collagen becomes steadily crosslinked and normal elasticity is lost. Joints may lose normal function (osteoarthritis) and bones lose strength (osteoporosis). The integrity of the complex immune system is not maintained.  Muscles also lose strength, and skin loses elasticity. The control of hormones, such as insulin, can be lost, and that leads to late onset diabetes, or other hormonal problems. Normally, defective proteins are degraded, but during aging many abnormal molecules accumulate. Some are in aggregates such as AGEs  (advanced glycation end products) and the age pigment lipofuscin. Deletions become common in the DNA  of mitochondria (organelles that generate energy), and chromosomal DNA accumulates gene mutations.

DNA is the template for RNA synthesis, and different RNAs have central roles in cellular metabolism. It is very well known that RNA synthesis is far less accurate than DNA synthesis (genetic replication), resulting in many errors. Most recently, it has become apparent that the normal control of gene expression – a field now known as epigenetics – can be lost during aging.

One of the remarkable features of aging is that the same age-related changes occur in animals with different life spans. The most widely studied experimental animals are rodents, such as the mouse or rat, both of which have a longevity of about three years. The information we have about humans comes largely from studies of age-associated diseases.  The many changes summarized in the previous paragraph  occur about thirty times more slowly in humans than in rodents. Much is known from veterinary health care about the aging of domestic dogs and cats. In these animals the same changes occur five or six-fold slower than in rodents, and six or seven-fold  faster than during human aging.  For a long time this was  a major problem that was not understood,  but now the explanation is known.

Rapid reproduction vs maintenance of the body

The energy available from food intake is used for 1) general metabolism, 2) for reproduction, and 3) for  maintenance of the adult body during the period when it is fertile. It is evident that 1) is similar in different species, but 2) and 3) can be very different. Thus short lived rodents invest heavily in rapid reproduction rather than the maintenance of the body. In complete contrast, animals’ longer lifespans have fewer offspring and invest much more in body maintenance. The inverse relationship between fertility and lifespan holds for innumerable mammalian species (see ref. 4 ).  This can also be investigated in the laboratory in studies which have shown in many cases that the efficiency of  a maintenance function is directly related to longevity (see refs 4 and 5). One simple example is the rate of cross-linking of the protein collagen: it  is about thirty times faster in the rat than in humans. The chemistry is much the same, but the external milieu surrounding the molecules is very different.

Major maintenance mechanisms include DNA repair, removal of defective proteins, the immune response, defenses against oxygen free radicals, wound healing, including blood clotting,  and several others. It is clear that all maintenance mechanisms depend on innumerable genes that in one way or the other relate to aging. The view that one or just a few genes determine aging and lifespan became obsolete many years ago.

The above brings us to the question: what would the anatomy and physiology of a complex animal that could survive indefinitely in a protected environment look like?  It would have to possess a wide range of regenerative mechanisms, so that cells, tissues and organs could be completely replaced. Even that would not be enough, because some organs, such as the heart or brain, have to function continuously throughout life. These organs have a very limited capacity for repair through cell division, so it would be necessary to have duplicate structures. Then one could be shut down for extensive repair and regeneration, whilst the second continued to function.  An immortal animal would need to have a very different structure from those that actually exist.  Aging is of ancient origin and it is built into the evolved structure and anatomy of the human body.  It is no more than science fiction to assert that this can be remodelled to bypass or reverse what is the intrinsic and inevitable end-product of its lifetime.

1. Holliday, R. (2009)  The extreme arrogance of anti-aging medicine. Biogerontology, 10, 223-228.
2. Hayflick, L. (1994; 2nd Edition 1996) How and why we age. Ballantine Books,New York.
3. Austad, S.N. (1996) Why we age. John Wiley, NewYork.
4. Holliday, R. (1995) Understanding ageing. Cambridge University Press, Cambridge.
5. Holliday, R   (2006) Aging is no longer an unsolved problem in biology. Ann. New York Acad. Sciences, 1067, 1-9.

Robin Holliday holds a B.A. in Natural Sciences and a Ph.D. in Genetics from Cambridge University. He has spent his career doing research in genetics, cell biology, and aging. Holliday’s last his book, ‘Aging: The Paradox of Life’ was published in 2007. He now lives in Sydney, Australia.

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