The comparative biology of aging, the study of aging in species with widely divergent life spans, is hoped to improve the catalog and understanding of important mechanisms of aging. It may or may not turn out to be the case that the biochemistry of long-lived species can give rise to practical therapies that slow aspects of human aging, at least in the near future of the next few decades. Engineering a human that ages more slowly seems a far more daunting task than the production of rejuvenation therapies that repair the known forms of cell and tissue damage that drive aging.
An alternative to comparing other species with humans is to take a collection of closely related species with divergent life spans and attempt to find out why they are different. Even if these species are very different from our own, aging evolved very early indeed in the tree of life, and there is the hope that lessons can be learned.
Even from fish, as today's open access paper discusses. The authors report on their initial investigation of rockfish species, with life spans varying from a decade to a few centuries. Any given strand of this sort of comparative biology research can progress for decades, gathering data without arriving at a clear picture as to the biochemistry and how it might be used to build new medicines for our species. One might look at the long-running investigation of proficient regeneration in salamanders, for example. It is definitely too soon to say what might be learned from a closer look at rockfish biochemistry.
Aging pathologies may be delayed, ameliorated, or prevented in aggregate by targeting the molecular foundations of the declines in homeostasis and function that arise over time. The knowledge of foundational targets suitable for such intervention remains limited, yet evolution has already leveraged such means, as is evident in the vast diversity of longevities in nature. Various species display aging-associated functional declines at wildly different rates and timings, including those that survive well beyond a human life span. As these traits are heritable and defining for many species, the underlying genetic mechanisms can be tracked through comparative genomic approaches.
There are many examples of long-lived animals. The Rougheye Rockfish, Sebastes aleutianus, is one such vertebrate species, with a maximum life span of over 205 years. Regardless of the aging mechanism - oxidative damage, proteostasis collapse, DNA damage, telomere/genomic maintenance, epigenetic drift, etc. - S. aleutianus resists the deleterious effects of age for over two centuries, enduring the variety of internal and external stressors assured with time. S. aleutianus is not the only rockfish lineage with this exceptional capability. The clade encompasses at least 107 extant species, ranging in maximum longevity from 11 to 205 years. Fortunately, multiple, independent lineages of rockfishes exhibit impressive life spans, imparting power into comparative approaches.
Our analyses reveal a common network of genes under convergent evolution, encompassing established aging regulators such as insulin signaling, yet also identify flavonoid (aryl-hydrocarbon) metabolism as a pathway modulating longevity. The selective pressures on these pathways indicate the ancestral state of rockfishes was long lived and that the changes in short-lived lineages are adaptive. These pathways were also used to explore genome-wide association studies of human longevity, identifying the aryl-hydrocarbon metabolism pathway to be significantly associated with human survival to the 99th percentile. This evolutionary intersection defines and cross-validates a previously unappreciated genetic architecture that associates with the evolution of longevity across vertebrates.