Fight Aging!

Today I'll point out an open access theory of aging paper that I found intriguing, given that it represents a fairly different viewpoint on aging, seemingly assembled from portions of other mainstream views on theories of aging. Almost every faction within the aging research community would find parts to agree with, parts to reject, and parts that will make you think things through. If you have strong opinions on theories of aging, you'll probably get a lot out of it. The contents defy short summary, but the more important points seem to be the idea of aging as an absence of process, as a lack of maintenance systems, and a rejection of the idea that the fundamental mechanisms of aging are as universal as the present mainstream consider them to be.

I've made the point in the past that lack of progress towards effective treatments on the part of the dominant paradigm in a field of medicine tends to lead to a lot of alternative, competing theorizing. It is much cheaper and easier to produce hypotheses than to undertake research programs and trials. Aging research has been stuck in this state for quite some time now, and, since the molecular biology associated with the progression of aging is immensely complex and poorly understood, there is a lot of room for theories to flourish without the possibility of effective contradiction. Cellular metabolism is in and of itself immensely complex and incompletely understood, and the effects of aging at the detail level are a large superset of all aspects of cellular metabolism, extending out to include the ways in which this intricate group of systems changes over time. So, and in recent years especially, there has been a great mixing and seeding of ideas when it comes to the fundamental level of theory regarding aging, and little ability to cull the field with clear and direct evidence.

The vast complexity of our biology, and the equally vast cost in time and money required to map it or manipulate it, is what makes the SENS damage repair approach to rejuvenation treatments very attractive. For all that the progression of aging is yet to be mapped in detail at the cellular level, for the reasons given above, the research community does have a good understanding and a good, defensible list of the causes of aging. This knowledge is complete enough to design and build effective treatments to block, repair, or reverse those causes, and those plans and research programs exist. Taking this path is comparatively cheap, in comparison to trying to understand or manipulate the operation of cellular metabolism, and effectiveness can be proven by building and testing. It is an end-run around gaps in knowledge and the expense required to fill them, taking the engineering approach to the problem. In fact, I see this as the most cost-effective path forward to determining the relevance of various theories of aging, and to answering many questions on the role of specific mechanisms in cellular biology in aging.

Given that we have the potential to address aging, to intervene effectively and extend life, I think that more important as a goal than theorizing. There is more to learn and more to gain by taking action in the present state of aging research, by building the comparatively cheap first wave of rejuvenation biotechnologies such as senescent cell clearance treatments, and then evaluating their effects. I think the character of the field of aging research is going to change dramatically in the years ahead as a result of the advent of SENS-style rejuvenation therapies. Theorizing will decline in favor of discovery and evaluation, with directions for research following on from the most effective therapies and their impact on metabolism. For now, however, on with the theorizing, and note that the quotes below are only small sections of a long but very readable paper:

Principles of alternative gerontology

Damage itself does not mean aging. Senescence is observed only if the effects of these negative events have not been eliminated. One can conclude, therefore, that senescence takes place only if allowed by low effectiveness of life programs of a particular organism. In other words, senescence is a result of allowing for manifestation of unavoidable effects of various adverse forces. As shown below, the degree of that allowance is different in various clades. Considering that the same forces can disrupt various organismal functions in varying ways depending on a particular organism, no universal mechanism of aging can exist. For example, oxidative damage to cells of Saccharomyces cerevisiae does not include various destructive processes resulting from peroxidation of polyunsaturated fatty acids, as the latter are not produced by the species. On the other hand, accumulation of rDNA circles noted in yeast is not found in human cells where an open mitosis process is observed.

Aging is not a genuine trait. Aging evolved only as a side effect of the choice of a particular life strategy of a clade. As such, it corresponds perfectly to the term "spandrel" introduced by Gould and Lewontin. With that in mind, gerontologists would be amiss to look for any universal mechanisms of aging because they simply do not exist. As a rational consequence, in order to explain the mechanisms of human aging, it is necessary to use the closest possible relatives of human beings as model organisms of gerontology. Accepting the interpretation that the incidence and nature of aging processes are side effects of the chosen life strategies rather than genuine traits suggests the need to transform the methodological approach to the phenomenon.

The problem of aging of animals practically does not exist in natural populations. Animals in the wild rarely survive until the symptoms of senescence become visible. As a biological science, gerontology is now strongly supported not so much for transcendental reasons, but rather because the age structure of the developed societies will soon create economic and social problems. The most important goal for such studies is to diminish the costs of population aging. Geriatrics needs a scientific basis for improving medical practice. Consequently, the aim of gerontology is to prevent the most life-devastating symptoms of senescence. Therefore, the basic role of gerontology, at least in the short term, should be identifying mechanisms that slow down and minimise the effects of senescence. In other words, the role of gerontology is not to extend the maximum lifespan above the limit characteristic for the given species. However, rather disappointingly, this is precisely what experimental gerontologists have been doing: rather than looking for mutants of various organisms in which the symptoms of senescence appear later or are less detrimental, they have been mainly looking for mutants with increased lifespan.

In human beings the term "aging" means appearance of symptoms of senescence and increased probability of death at advancing age. However, after an analysis of various life forms, one can conclude that senescence and unavoidability of death in general are at least partly separable in mortal organisms, while numerous groups of simpler animals are biologically immortal. The phenomenon of senescence is observed in those species or life stages of organisms that cannot by principle remove the damage done by various adverse extrinsic and intrinsic forces. An analysis of differences in life programs among various taxonomic groups of animals as well as within a particular group allows for a generalisation that there are three main aging phenotypes.

The first encompasses representatives of the simplest animals like sponges, cnidarians, annelids, nemerteans or echinoderms that show biological immortality, that is, lack of intrinsic causes of death. These animals rarely manifest symptoms of senescence. The reason for their immortality is the ability to reproduce agametically (besides sexually), resulting from the enormous ability of cell replacement and regeneration. The second group is represented by the organisms which, while being mortal, show no visible symptoms of senescence. This phenotype is a consequence of the constant increase in body size after reaching sexual maturity. Because proportional growth requires constant availability of most of organismal-level developmental programs, such constant growth is accompanied by high cell replacement and regeneration ability. The best known representatives of that group are crustaceans and molluscs among invertebrates and fish and reptiles among vertebrates. Constant growth corresponds to the adolescence period of mammals or larval stages of insects as these animals do not show organismal-level senescence. Consequently, continuously growing animals are "young forever". The third and very diverse group is represented by insects and roundworms among invertebrates and mammals and birds among vertebrates. These animals show evident symptoms of senescence but differ in longevity. Their adult representatives live for a very short time. The presence of symptoms of senescence in these animals results from their primary life programs. Their sensecence is a consequence of the lack of, or very limited, cell replacement and regeneration mechanisms.

The practical conclusion that can be drawn from these considerations is that lack of universality of aging suggests a fundamental change in approach to gerontological problems. Instead of looking for mutants of simple and evolutionarily distant species with increased lifespans, gerontology should focus on finding factors alleviating the most life-disrupting effects of senescence.