April 2017
Ivan Obolensky

One of the byproducts of living is aging. Paradoxically, in spite of the hard evidence we see in the mirror each morning, age seems to have a positive effect on how we view the world. Older adults are less depressed and less affected by negative information than the young. Whether that is the result of experience or biological change is unclear.¹ Naturally, we want more life, and our wishes for more appear to have been answered. We’re living longer on average as a species, and that is changing the world.

The trend is toward older populations who now wish to be youthful physically, or at the least, in the same shape today for as long as possible. Current research holds great promise, but so far few practical results have been forthcoming. That does not mean that our desire to want to live longer has diminished. Nor does it mean that there is any lack of hype regarding various drugs, potions, therapies and lifestyle changes that cater to those desires regardless of actual effectiveness.

This article will look at aging in terms of recent research from a cellular and microbiological perspective as well as the most fundamental aspect of aging: why do we age at all? The fact is not all species age. Lobsters, rockfish, and tortoises show no signs of aging. We would like to know why we do, and they don’t.

To begin, aging is a process that is different from our state of health. Aging could be defined as a progressive decrease in functionality. Health is the state of being free of illness or injury. The two are related in the sense that aging leads to reduced reproductive capacity and to susceptibility to illnesses, such as heart disease, arthritis, cancers, diabetes, Alzheimer’s, Parkinson’s, and senility. The primary difference is that health is a static quality, a state of being. To age is to experience a constant headwind that leads to an inexorable decline in our health.

From a quantitative perspective, overall health of a species is reflected in the Initial Mortality Rate (IMR). It is the probability of death given a population of a species at a specific age. The IMR for humans is different for different age groups. In infants, the IMR is high because they are more susceptible to disease and mortality from birth defects. After birth, the IMR decreases rapidly until it bottoms at the age of ten, meaning that the likelihood of death in humans is lowest and the life expectancy highest for those who are ten years old. After ten, the IMR increases rapidly (probably due to hormonal changes and teenage rejection of more conservative restraints) until twenty to thirty years of age, at which point it stabilizes.

In another context, women have a lower IMR than men, meaning women are for the most part healthier than men. Given the same age, women die less often for whatever reason. Aging, on the other hand, is measured by the Mortality Rate Doubling Time (MRDT) and is more or less constant from age 30 to 100. Human mortality doubles every 8.66 years and is the same for men and women Although women start with a lower IMR, they age at the same rate as men.

Not every species has an MRDT. Bristlecone pines grow in high rocky areas devoid of predators and are estimated to live over 5,000 years. They have no MRDT and show no decrease in reproductive output with age. Death is likely only due to lightning strikes or environmental cataclysms as opposed to internally generated breakdowns.²

Old Age is never the primary cause of death. Humans die from organ failure as the result of aging. One characteristic of those over 110 years of age is that their organs age uniformly rather than one being weaker than others, but inevitably, one of them fails and death results.

Why we age is an interesting question. It seems to fly in the face of the theory of evolution in the sense that why would nature select for a process that reduces reproductive capacity and increases mortality? There are several theories on this. One put forward by Peter Medawar in the 1950s was that natural selection declines with age. Genes that help the species early in life are preferred over those that aid a species in later periods.

For example, suppose due to predation, a species has a life expectancy of one year. Nature would favor genes that would allow for early reproduction. Genes that might be harmful later on could remain in the population, provided they were advantageous to the species at the beginning. An example is the extravagant plumage of peacocks and others that aid in reproduction but are a hindrance in escaping predators.

Genetic drift and mutations can also create genes that will be harmful in later years but are less of a factor in terms of natural selection because very few of the species live that long. This concept also allows for genes having an early positive effect, such as promoting rapid growth, but create a negative effect in later years by inducing cancers and tumors.

As a model, this seems to work well but is not all-inclusive. Certain species of turtles increase reproductive capabilities and quality of their offspring the longer they live, while the probability of survivorship actually increases over time.³

They are the exception, not the rule. Since even single-celled organisms such as bacteria were found to age, it would follow that how individual cells replicate, and for how long, are factors in aging. The human body is composed of some 37.2 trillion cells, and how our microscopic parts handle aging ought to determine to some degree, the aging of the whole. This concept is part of the Programmed Theory of Aging.⁴

As a point of clarification, the rate at which we age and the length of our possible life spans are not the same thing. Humans may be living longer, but doing so does not mean we are aging less.

Aging is like driving a car. We are driving longer distances but not necessarily slower, and the reason is remarkable. It is not because of our lifestyles or because today we are innately so much healthier. It is because the number of deaths from infectious diseases that had previously curtailed the probability of a long life has been reduced significantly over the last one hundred years.

Using the car analogy, we humans are suffering less random disease accidents, allowing us to cover longer distances rather than because our cars are so much better, or because we are such good drivers. The models we drive today are the same ones we drove 10,000 years earlier. Still, we try for improvements and want to drive for as long as possible.

At one time, it was thought that all cells could live forever by dividing (undergoing mitosis) indefinitely.

In 1962, Dr. Leonard Hayflick discovered that contrary to this belief, human and animal cells can replicate only forty to sixty times. This is called the Hayflick Limit*, although there are some exceptions.⁵

Once this limit is reached, a cell will either trigger a programmed self-destruction called apoptosis or the cell will lapse into Replication Senescence (RS). Cells that have reached this point (RS) can no longer divide to create new cells although they can continue to exist in the body for quite some time. One of the factors that limits the number of times a cell can replicate is determined by the telomere region at the end of a cell’s DNA strand.

To prevent telomere shortening from replication affecting the actual working portion of DNA, nature has added end pieces (telomeres) that do not code for any protein but act like the tape leader in old-fashioned tape recorders or film projectors.

As cells divide to replace old ones and grow the organism, the telomeres erode. In 1998, scientists from the Geron Corporation established that telomere shortening gave rise to RS. They also determined that the enzyme, telomerase, elongates the telomeres, corrects telomere erosion, and extends the Hayflick limit for individual cells. This resulted eventually in a Nobel Prize award. ⁶

At this point, it is important to establish the difference between two concepts: in vitro and in vivo. Both come from Latin. In vitro literally means in glass while in vivo means in the living. Cellular processes established in vitro can be very different when carried out in vivo due to the complex interactions between systems, different cellular environments, organism stresses, age. These are just a few factors that complicate, obscure, and often nullify in vitro results. It is this difference that has mitigated the often positive findings that are reported by various news services. There is a very long step from in vitro to in vivo results.

Telomere erosion is not the only factor that can accelerate or trigger cellular senescence. Another explanation is called the Wear and Tear or Damage-based Theory of Aging. The theory holds that adverse factors in the environment precipitate and advance aging. An example of this is oxidative stress.⁷

Hayflick’s studies were repeated using 3% oxygen levels rather than the 21% oxygen content of the atmosphere at sea level to closer approximate actual cellular physiological conditions. At reduced oxygen levels, cellular Hayflick limits were extended by an additional twenty replications. When oxygen was increased to 30%, the number of replications fell, and when pushed to 50%, the cells died.

The phenomena of oxygen levels creating early senescence is called Stress-induced Premature Senescence (SIPS). The cells in the human body are not homogeneous. There are not only many different types of cells but certain areas of the body are denser from a cellular perspective than others. With no stress, cells proliferate, but as oxidative stress levels increase, cells respond by experiencing replicative senescence, apoptosis, or in extreme cases, necrosis, (death by external causes.)⁸

From the above it would seem that to counteract the effects of aging all we would need to do would be to consume antioxidants such as Vitamin C in large amounts as well as the enzyme telomerase, all of which are readily available, but that would be premature. There is little evidence that either of these work and in some cases they may actually accelerate mortality.

Human bodies are complex. Most cellular research is done in vitro as opposed to in vivo and with good reason. Extending the findings into workable protocols that can allow the results to be tested on human subjects is difficult, expensive, time-consuming and often contradictory. Research using mice as subjects is routine, but results in one species are not always valid in another, leading to mixed results.

Human systems can also be contradictory. At first glance it might seem advantageous to limit cellular senescence and apoptosis, but that would be premature as well. One of the indications of aging in many species is a proliferation of cancers. Both apoptosis and cellular senescence work to prevent the possibility of replication errors.

According to a recent study, nearly 66% of genetic mutations that develop into cancers are the result of random errors in the replicative process rather than the result of environmental, hereditary or life style factors.⁹ One explanation for telomere shortening is that it signals that mutations are more likely with a particular cell and that the better course is to either have the cell cease replication or to be taken off line altogether. By preventing or limiting these processes, it is possible that cancer growths might proliferate rather than be curtailed.

Although we cannot look to supplements, miracle drugs, and other means to extend life at this time, there are regimes based on our current knowledge that promise to extend life spans. One is called calorie restriction (CR).

As the name implies, CR involves reducing food intake while maintaining the intake of vitamins and minerals. Several animal studies have shown that CR extends life spans and may even delay the rate of aging, although this is not universal across all species. Studies on monkeys have shown that CR may extend life, but may not in individuals who are already eating a moderately healthy diet.

CR seems to work in human subjects, but there are side effects. There is mental stress from being hungry all the time and one can only wonder whether the lack of energy, anxiety, and less aliveness makes undertaking such an activity ultimately worth the effort.¹⁰

Currently, the scientific results, although extending our knowledge, have yet to yield any workable and easily accessible methods to counter aging regardless of what has been printed.

In the end, how we react to the fact that we are getting older is an individual matter of choice. Perhaps, the best and only advice is to enjoy the time we have by avoiding negativity, exercising, hydrating, eating moderately, and living our lives to the full. In the meanwhile, research continues.

 

* Hayflick’s studies were done in vitro in three phases. Phase I was the primary cell culture, and it was allowed to grow and cover the inner surface of a culture flask. Once the entire surface was covered, the cells stopped multiplying. In order to continue growing, they had to be sub-cultivated. This was Phase II. The culture medium was removed and trypsin, a digestive enzyme, was added to dissolve the bindings between the cells. A growth medium was added and then the mixture was pipetted into two or more flasks. Cells attached themselves to the new flask surfaces and started dividing again until the next sub-cultivating process was needed when the flask surface was covered. Phase III started when the cells began to divide more slowly. Eventually, they stopped altogether after an average of 50 cumulative population doublings. This growth-arresting phase after a period of proliferation established the Hayflick Limit or what became known as Replicative Senescence.

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1. Goudarzi, S. (2007) Older People More Optimistic, Live Science. Retrieved April 3, 2017 from http://www.livescience.com/4324-older-people-optimistic.html.
2. Magalhaes, P. (2013) What is Aging? info. Retrieved April 3, 2017 from http://www.senescence.info/aging_definition.html.
3. Magalhaes, P. (2013) The Evolutionary Theory of Aging. info. Retrieved April 3, 2017 from http://www.senescence.info/evolution_of_aging.html.
4. Pachana, N. (2016) Ageing: A Very Short Introduction. Oxford, UK: Oxford University Press.
5. Magalhaes, P. (2014) Cellular Senescence. info. Retrieved April 3, 2017 from http://www.senescence.info/cell_aging.html.
6. Magalhaes, P. (2014) Telomeres and Telomerase. info. Retrieved April 3, 2017 from http://www.senescence.info/telomeres_telomerase.html.
7. Magalhaes, P. (2014) Damage-Based Theories of Aging. Senescence.info. Retrieved April 3, 2017 from http://www.senescence.info/causes_of_aging.html.
8. Pachana, cit.
9. Harris, R. (2017) Cancer Is Partly Caused By Bad Luck, Study Finds. Retrieved April 3, 2017 from http://www.npr.org/sections/health-shots/2017/03/23/521219318/cancer-is-partly-caused-by-bad-luck-study-finds.
10. Magalhaes, P. (2014) Caloric Restriction. info. Retrieved April 3, 2017 from http://www.senescence.info/caloric_restriction.html.

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© 2017 Ivan Obolensky. All rights reserved. No part of this publication can be reproduced without the written permission from the author.