Why are long-lived species long-lived? The prevailing view of the evolution of aging is that degenerative aging is the result of natural selection operating more strongly on early life reproductive success than on later life reproductive success for individuals. Natural selection produces biological systems that are front-loaded for immediate success and fall apart over time (cellular senescence is a cancer suppression and wound healing strategy, but causes tissue dysfunction as senescent cells accumulate), or simply cannot function indefinitely even if they were perfectly maintained (the adaptive immune system devotes ever more cells with passing time to the memory of specific threats, at the expense of cells capable of attacking those threats). At the level of individual biological mechanisms, antagonistic pleiotropy takes place: mechanisms are selected for reproductive success in early life, but those same mechanism cause harm in older individuals.
In today's open access paper, researchers suggest that the exceptional longevity of any given species is largely an accidental byproduct of adaptations to a given evolutionary niche. This view has been discussed in past years in the context of naked mole-rats and related species, which are resilient to the low oxygen environment found underground. The mechanisms needed for that resilience likely also contribute to the exceptionally long life spans exhibited by these species. Similarly for many bat species, the mechanisms required for resistance to viral pathogens and sustaining the high metabolic demands of flight likely contribute to a much greater longevity than is found in similarly sized mammals. A counterargument is the case of our own species. We live longer than other primates, and the grandmother hypothesis suggests that this is because culture and intelligence allows old individuals to contribute to the reproductive success of their descendants - our relative longevity amongst primates is not an accidental byproduct of evolutionary adaptation, in other words, but actually selected.
The ability of an organism to survive in a specific ecosystem as a result of changes to its behavioral, physiological, morphological, and genetic response is called adaptation. Ecological adaptation strongly underlies lifespan extension in lineages and species where longevity has been observed despite differences in species ecosystem, morphology, and complexity. Predictably, all long-lived species have low extrinsic mortality due to the nature of their habitat or have evolved mechanisms to evade predators and imminent dangers. However, as much as this ability is expected to contribute to lowering extrinsic mortality, it neither explains the variation observed in lifespan or mechanisms through which lifespan is regulated.
Long-lived species are now known to exhibit efficient adaptive responses in essential pathways that contribute to lifespan with evidence of enhanced genome maintenance, DNA damage response, and repair attributing to their longevity. Thanks to affordable genome sequencing, the availability of genome data revealed widespread adaptation in the genomes of long-lived species where positive selection, rare sequence variants, and genome duplication contributed to ecological adaptation, the evolution of body size, and disease resistance. Although mechanisms of extended lifespan of these species are currently unclear, emerging evidence from genomic analyses points to the important role of species adaptation in longevity.
Although there are a number of genetic adaptions in the wild that contribute to lifespan extension, population genetics postulates that genetic changes are hardly to be fixed if such genetic changes do not increase fitness during long-term evolution. Nevertheless, we posit that strong selection acts to maintain these changes, leading to long lifespans in living organisms. We propose that extended lifespan is not by itself under selection but rather an epiphenomenon (by-product) of species adaptation, a phenomenon we have termed here the adaptive hitchhike model. First, the model implies that a new pleiotropic mutation, with one of its effects being extended lifespan, could be favored by natural selection due to its advantage to some other trait and therefore becomes fixed. Second, the model also applies to new pro-longevity mutations that occur at sites closely (or functionally) linked with the allelic sites under selection; if a new pro-longevity mutation arises at a site that is linked to an adapted genome region, natural selection may cause an increase in allele frequency and fix this pro-longevity mutation through linkage and allelic associations.
Therefore, the adaptive-hitchhike model suggests that the selective constraint acting on the genomic region associated with adaptation and fitness is largely responsible for non-random beneficial pro-longevity effects. For example, patterns of selective sweep across loci of close proximities were reported for adaptation to altitude among the Tibetan population, and a further association was found between longevity and hypoxia response in this same population. In other cases, natural selection might act on an already existing but neutral mutation through a sweeping selection; therefore, if neutral alleles responsible for lifespan extension are close enough to other alleles under selection, the chances of recombination are slim, and together, they become fixed in the population.
This model could be mainly summarized in the following ways: (1) Some adaptive genetic changes could have dual functions, i.e., adaptive and longevity effects. (2) A pro-longevity mutation could come under selection and become fixed through direct selection or linkage and allelic association. (3) In the same way that a pro-longevity mutation could become fixed, a geronic (pro-aging) mutation could also become fixed and lead to a shorter lifespan. (4) In the case where environmental pressure is relaxed, pro-longevity effects may be lost. Therefore, our adaptive-hitchhike model of longevity of animals could be tested by (a) identifying pro-longevity effects of genetic changes that respond to adaptation and (b) detecting signals of linkage disequilibrium between adaptive and longevity variations. The novelty of this model is that it gives a key role to such nucleotide substitutions and loci with dual functions. Functional evaluation and validation of adaptive nucleotide substitutions with the pro-longevity potential could provide answers to the century-long questions surrounding the evolvability of animal lifespan.