Fight Aging!

Rate of living theories of aging emerged from the observation that metabolism is generally slower in larger, longer-lived species. There are enough exceptions to disprove any specific hypothesis regarding what exactly might limit life span in species with a fast metabolism, however, and for this and other reasons rate of living theories fell to the wayside, somewhere along the way towards the development of a modern understanding of cellular biochemistry. Nonetheless, we are left with the observed that, yes, larger species tend to live longer, and yes, species with slower metabolisms also tend to live longer. Exceptions aside, that does suggest that something is there to be learned.

Here, researchers propose that the count of respiratory cycles over the course of a lifetime is the underlying roughly constant number that links all of the observed correlations of mass and metabolism across the majority of species. One can hypothesize, as was the case for the free radical theory of aging, that the apparent evidence for rate of living theories must say something about evolutionary limits placed on the amount of oxidation and cell damage an organism can sustain. This is, in turn, because oxidative molecules produce DNA damage at some pace, and there may be an evolutionary limit on the amount of mutational damage that can be sustained. At the same time, mutational damage is necessary for evolution to occur, and organisms that sustain more mutational damage will evolve more rapidly, potentially outcompeting those that evolve more slowly. We may be observing the result of optimization into a narrow window of possibilities.

On the causal connection in lifespan correlations and the possible existence of a 'number of life' at molecular level

Understanding the relevant processes that drive ageing and determine the longevity of organisms has been a subject of research for several decades, with many proposed theories of ageing that can be divided by the level of the primary factor: molecular, cellular, system, and evolutionary level. One of the theories at molecular level, is the somatic mutation theory of ageing, in which accumulation of mutations in the somatic DNA over time eventually cause a functional decline. This theory has been recently supported by, that reported a strong inverse relationship of the somatic mutation rate per year with species lifespan, with no other life-history trait showing a comparable association. Reference also found that the lifespan mutation burden varied only by a factor of around 3, despite widely different life histories among the species examined (i.e variation of around 30-fold in lifespan and around 40,000-fold in body mass). This result, established among the species, can be interpreted as support for a approximately constant total number of mutations over the lifetime of mammals and thus, being some kind of 'Number of Life' which effectively predetermines the extension of life.

Another 'Number of Life', to be approximately constant for different classes of living organisms (not only mammals), has been also proposed recently: the total number of 'respiration cycles' in a lifespan, Nr, which generalize the well-known empirical relation between the heart frequency and the lifespan, namely Nh the total number of heartbeats in a lifetime. In this paper, we study the causal connection in lifespan correlations, showing that six phenotypic traits (metabolic rate, mass, female and male sexual maturity, litter size, and heart frequency) acting at the system level, are all related to lifespan thru the existence of an approximately constant number of respiration cycles in a lifespan.

Consistent with a direct proportionality between the somatic mutation rate and the respiration frequency, which might suggest a possible origin of the constant number of cycles per lifetime at molecular level, thru being a manifestation at system level the fixed number of end-of-lifespan mutation burden at molecular level (or vice versa). One possible link between the respiration process and the rate of somatic mutations, might be through the byproducts of the respiration process, such as free radicals and oxidants that are candidates traditionally hypothesized to be responsible of the ageing process, as far as production rates of those byproducts of respiration determines the rate of somatic mutations.