Why is degenerative aging near universal in species, when the few (probably) actually immortal species such as hydra show that aging isn't an inevitability, while negligibly senescent species such as naked mole-rats show that youthful health can be maintained throughout much more of life and old age than in our own species. There are two big tent camps when it comes to views on the evolution of aging. The first is a fairly static camp, in which aging is a seen as a side-effect of selection pressure falling most heavily on the performance of young individuals; evolution selects changes that support early reproductive success, regardless of the consequences to later health. Aging is a side-effect of what is called antagonistic pleiotropy, negative consequences of selected changes.
The second camp sees aging as an evolutionarily selected program, rather than a side-effect of evolutionary processes, is far from unified in what that actually means, and for the past twenty years has been undergoing change and ideation at a fair pace. The most discussed ideas in programmed aging in the 2020s are quite different from those of the 2010s. There is even a faction between the two camps that blends together concepts of antagonistic pleiotropy and programmed aging into variants of what is presently called the hyperfunction theory of aging. It is sometimes hard to keep track of who is presently in favor of what on this side of the fence, but the papers usually make for interesting reading.
Does this all have practical consequences? For a while back in the day it was possible to say yes, because it looked like epigenetic changes were a far downstream consequence of the actual causes of aging, the underlying cell and tissue damage, and programmed aging advocates usually argued for therapies to focus on changing gene expression from aged to youthful patterns. From the aging-as-damage perspective, that was exactly the wrong thing to do if large gains in health were the intended goal. Now the waters are much less clear. Epigenetic changes may in fact be much closer to the root causes of aging, as research into the consequences of stochastic mutational damage illustrate, and the sorts of therapy proposed by researchers who favor programmed aging versus the antagonistic pleiotropy viewpoint are no longer all that different. Other factors, largely economic, are now arguably more important in determining which approaches make the leap from laboratory to industry.
Epigenetic clocks and programmatic aging
Recent years have witnessed exciting advances relating to methylation clocks and programmatic aging theory. We have highlighted here the convergence of these two paths of progress, and described several new ideas arising from this convergence. Understanding of the biological processes of aging that methylation clocks correspond to has lagged behind the recent rapid progress in clock characterization. Several features of clocks suggest that this hidden biology involves developmental processes.
Recently developed programmatic theories offer a framework of ideas within which such developmental aging mechanisms can potentially be understood. Such a framework includes explanations for how such clocks evolve, the programmatic mechanisms in which they act, and how those mechanism contribute to late-life disease. Central to this framework is the hypothesis that epigenetic and developmental changes occurring throughout life history are part and parcel of the same process. According to evolutionary theory, genes exhibiting antagonistic pleiotropy, that are beneficial early in life yet detrimental later on, may be favored by natural selection, causing aging. In the context of programmatic theories, the basic hypothesis is that developmental gene action and processes that are beneficial earlier in life continue later in life, in a futile fashion, becoming detrimental and pathogenic.
Here we explore how recent discoveries about methylation clocks cohere with the developmental theory of aging. We present several new perspectives, questions, and speculations arising from the cross-referencing of these two subjects, and argue for the timeliness of interdisciplinary integration of biogerontology with developmental biology. Central to these ideas is the hypothesis that epigenetic changes occurring throughout life history (including ontogenesis and senescence) are part of wider developmental changes. We have elaborated upon this explanatory framework, introducing new terminology (including the distinction between onto-developmental and maturo-developmental processes). Hypotheses proposed include the regulation by polycomb proteins of a trade-off between developmental fidelity and plasticity, and the presence of a conserved developmental sequence as a major, previously unseen element in the aging process. These suggestions provide examples of the sort of thinking that is possible by combining ideas from evolutionary biology, biogerontology, and developmental biology, in what we have described as a developmental gerontology or devo-gero approach.
View the full article at FightAging
