Changes in Regeneration Across a Lifespan in Various Species

Here I'll point out an open access review paper that looks over what is known of regenerative capacity and aging in a variety of species in which individuals have quite different trajectories of health and degeneration over a life span. A whole section of the research community is very interested in cataloging the processes of aging as they occur in other species: the comparative biology of aging. Near all species age in the sense of suffering growing damage, degeneration, and frailty as we do, but life spans can be wildly different even in very similar species. A factor of ten difference in life span between near relatives is not unknown; consider the three years of ordinary laboratory rats versus the thirty years of naked mole rats, for example.

Within the context of a given life span, the panoply of well-known species exhibit enormous differences in susceptibility to specific forms of disease and dysfunction. Some species of whale can live for centuries, have many times as many cells as we humans, and yet experience similar or lower rates of cancer than we do over our shorter life spans. Rats and mice are little cancer factories, but naked mole rats seem entirely immune to cancer. They are further considered one of the negligibly senescent species, a list that includes rockfish, turtles, possibly lobsters, and a number of lower organisms such as hydra that might even be entirely ageless in a suitably forgiving environment. Individuals of these negligibly senescent species typically show next to none of the familiar progressive decline of aging until the very end of their lives.

Moving on to consider the matter of regeneration from injury alone, a number of species with the capacity to regrow organs without scarring, such as salamanders and zebrafish, also exhibit little or no reduction in regenerative capabilities over the course of a lifetime. Hydra feature here again as paragons of always-on regeneration, capable of regrowing and replacing any part of their structure if given the chance to do it. It is fair to say that there is a suspiciously good correlation between negligible senescence and greater regeneration when surveying the animal kingdom.

Some research groups aim to go beyond observation in order to mine the biology of these unusually regenerative, long-lived, and cancer-resistant species. They are in search of the basis for potential therapies, ways to port over these varied benefits to the less capable and more vulnerable human biology. It is an open question as to whether or not it will be practical to do this in the near future in any particular case. It depends absolutely on the details, and those have yet to be fully deciphered, even for salamander regeneration, which has been studied with the tools of modern biotechnology for many years now.

Changes in Regenerative Capacity through Lifespan

From the onset of development until the end of their lifespan, most organisms experience a progressive decline in their regenerative abilities. From a biological perspective, regeneration can be subdivided into the ability to replace lost or damaged cells, which includes tissue turnover and limited injury responses found in the majority of organisms including mammals, and the ability to regenerate complex structures, which is mostly absent in mammals but finds expression in a number of other animals. During aging, mammals exhibit changes in their ability to regenerate vital biological structures such as the vascular, nervous, muscular, haematopoietic and skeletal systems as well as many organs and cell types, which correlate with the overall organismal decay.

Although metazoan species exhibit a diverse range of lifespans, it is notable that in most organisms studied so far there is a strong association between the decline in regenerative capacity and the aging process. Indeed, it has been proposed that aging results from the inability to maintain proper tissue structure and function due to insufficiencies in regenerative capacity. Hence, regeneration and aging could represent two sides of the same coin. This idea is supported by the existence of organisms with extreme regenerative capacities, such as planarians and salamanders, which exhibit negligible signs of aging, as indicated by the lack of measurable functional declines with age.

The principles that underlie the decline in regenerative abilities through lifespan are currently being unravelled. However, it is already clear that both cell-intrinsic (such as cellular senescence) as well as cell-extrinsic factors (such as alterations in the regenerative environment) play significant roles. Notably, these factors show extensive overlap with those known to underlie the aging process, highlighting the interconnection between aging and regeneration and stressing that therapeutic approaches designed towards enhancement of regenerative abilities could also result in considerable health/lifespan improvements.

This review discusses the nature of the changes in regenerative abilities that take place through lifespan and across phylogeny, the factors which underpin such changes and the avenues for therapeutic interventions which leverage off this body of research. A particular emphasis is placed on knowledge derived from the classic regeneration models, organisms capable of extensive regeneration of complex structures in which age related declines in regenerative abilities are not observed, as this can shed light on important mechanisms with potential therapeutic application. It is becoming increasingly clear that certain factors, such as cellular senescence, constitute common denominators which impact on various regenerative systems and thus hold great promise for clinical intervention. However, despite the progress made so far, it is also evident that we are far from reaching a full understanding of the interplay between regenerative capacity and aging. Further research will benefit from studies in both vertebrate and invertebrate models of age-related regenerative decline, as well as from work in organisms where these capacities are not affected by aging, such as salamanders. Together, these approaches will deliver important insights into the variations of regenerative capacity through lifespan.

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