Species differences: The dark matter of longevity genetics

Mainstream genetics of ageing and longevity studies modest longevity interventions known from short-lived model organisms, such as caloric restriction or rapamycin in nematodes or mice; and the evolutionarily conserved, nutrient-sensing metabolic fine-tuning pathways involved, such as insulin-like signaling (ILS) and target of rapamycin (TOR). Yet these effects are dwarfed by what evolution can do: a calorically restricted mouse lives 4–5 years; but a naked mole-rat lives decades, while a bowhead whale or an ocean quahog live centuries.

The study of species differences in ageing and longevity is an emerging field. It requires non-classical genetic methods, including comparative genomics to generate hypotheses and gene-editing or cell culture experiments to test them. So far it has yielded some answers, and more questions: for instance, we know ocean quahog proteins resist misfolding, but we don’t know how; and we know that elephants have extra pseudogene copies of the tumour-suppressor TP53, but whales don’t. It has suggested some roles for old friends, such as the ILS pathway in microbats; as well as for new friends, such as FAM126B, a barely-studied protein related to hyccin, in mammals; and OBSCN, a giant gene with many isoforms due to alternative RNA splicing, in Pacific rockfish.

Poster references

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Kolora, SRR. et al. (2021). Origins and evolution of extreme life span in Pacific Ocean rockfishes. Science 374: 842–847. https://doi.org/10.1126/science.abg5332

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Poster permissions:

(Seluanov et al., 2018, Fig. 5): permission not sought to reproduce online.

(Lees et al., 2017, Fig. 4A): "Permission is not required to use original figures or tables for noncommercial and educational use (i.e., in a review article, in a book that is not for sale) if the article published under the exclusive PNAS License to Publish. ..." [source].