Fight Aging!

As noted in a prior post, a great deal of theorizing on aging takes place in the research community. We should expect this as the natural outcome of the study of a very complex and still only partially understood system, which is to say the operation of biology and how that changes over time in any given individual, how it differs between species, and why near universal processes such as aging or the calorie restriction response exist. It is a vast field of study into which scientists have made some inroads: the mountains of data and toil of thousands of researchers today is but the foothills of what is to come in the decades ahead. Coming to a full accounting of our biochemistry is the Great Work for this century, but fortunately we could choose to strike out directly for rejuvenation treatments without needing that complete understanding of aging at a detailed level. As outlined by the SENS research proposals, the scientific community does in fact have a well defined and defensible list of the fundamental forms of damage that cause aging, and can envisage in some detail the therapies needed to repair them - and thus reverse the course of aging. All that needs to happen is for more funding and attention to be directed to that path, away from the natural scientific inclination to dismiss applications of their work and focus instead on completing the grand catalog of metabolism and aging, the aforementioned Great Work.

There is some debate in the aging research community over whether cellular and molecular damage is in fact the root cause of aging, essentially a complex form of wear and tear by stages in a self-repairing system of many interacting parts, or whether damage accumulates with age because of the operation of an evolved genetic program. The former is very much the majority position, and baked into the repair approach to rejuvenation, but the latter is a large enough minority to be generating all sorts of internal schisms and hybrid theories in and of itself. This ties back into ongoing investigations into why aging evolved at all, which has become an especially interesting question over time given the growing list of species wherein individuals do not seem to deteriorate with age as we do, even though they fail at the end, such as naked mole-rats, and a very few species whose members might not age to death at all, such as hydras.

This very readable paper from the Russian research community, where programmed aging theories are much more popular than is the case in the English speaking world, meanders through a range of topics with no particular central thesis: what is known of naked mole-rats and their peculiarly age- and cancer-resistant biology; reconciling differences between scientific factions favoring programmed aging versus aging as damage accumulation; thoughts on how aging may accelerate evolutionary change and thus be beneficial for species survival; oxidative mechanisms in aging; and more. It is all interesting, and much of it still relevant insofar as it considers data on biological mechanisms rather than their causes, a useful insight into the thinking of the programmed aging side of the research community. A few snippets are quoted below:

Review: New Data on Programmed Aging - Slow Phenoptosis

The concept of aging as a special biological program provides an alternative to the hypothesis of random errors. According to this concept, aging is a particular case of the phenomenon of programmed death of an organism, phenoptosis. Aging is assumed to accelerate evolution since over the years the organism weakened by aging is subjected to increasing pressure of natural selection. For example, a fox is hardly a factor of natural selection for young hares, which run much faster than the predator. As noted by Aesop, a hare will always run away from the fox because for the hare it is a matter of life and death, and for the fox - of a dinner. However, age-related sarcopenia reduces the hare's running speed, so the fox gets a chance to win the race. As sarcopenia is one of the early signs of aging in mammals, developing well before senile infertility, foxes could accelerate the evolution of hares by eliminating the slowest and least clever individuals.

The biological literature contains many examples of phenoptosis enhancing the organism's ability to evolve (their "evolvability"). Along with aging, they include different mechanisms providing, on one hand, increase in offspring diversity (which is beneficial for the search for new properties) and, on the other hand, the conservatism of inheriting of already acquired useful traits. These mechanisms, while being undoubtedly useful for evolution, are often counterproductive for the individual, as in the case of aging.

The great physicist Leo Szilard believed the reduction of tissue and organ cellularity to be the main cause of aging. According to Szilard, the problem of aging is not so much connected to the fact that each of our cells works worse, but that the number of these cells dramatically decreases with time. Senile sarcopenia, i.e. the reduction of the number of cells (myofibrils) in skeletal muscles, is a typical example of this phenomenon. Age-related weakening of the quality control could save many cells that otherwise would have been destroyed and thus would have exacerbated the reduction of cellularity. Accumulation of cells with random errors in DNA and proteins in the tissues of aging organisms would be a side effect of such a strategy. Gradual weakening of quality control, resulting in the accumulation of errors, is indeed observed in the course of aging; it serves as the main argument for the supporters of aging as the result of random damage. However, we should not forget that reduction of cellularity is likely to have been originally programmed in the genome as the final stage of ontogenesis. Thus, we come to the situation when aging, having begun as the result of the relevant program, is gradually turning into the process of accumulation of random (stochastic) damage to biopolymers, which remain unnoticed by the weakened systems of quality control of these polymers.

It is clearly the case that a few species have evolved death programs of one sort or another, such as a sudden collapse of tissue maintenance or organ function. Salmon are probably the most familiar example, but they are not the only species to decline and die very rapidly following reproductive efforts. The debate between research factions is not over whether these programs exist at all in the natural world, but whether they are usual, and more specifically whether aging in humans and other higher mammals is guided by programs or not. This is relevant to research strategies because efforts to produce rejuvenation should be targeted at primary causes, not secondary and later manifestations of aging.