Species differences: The dark matter of longevity genetics

• Main Author: Bahry, David
• Format: Conference Object
• Language: English
• Published: Zenodo 2022
• Subjects: senescence; ageing; comparative biogerontology; cancer; protein misfolding; long-lived species; obscurin; hyccin; Pacific; Finch; Austad; bowhead whale; Ocean quahog
• Online Access: https://doi.org/10.5281/zenodo.7090086

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 andlongevityis 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 Austad, SN. (2022). Methuselah's Zoo: What Nature Can Teach UsAbout Living Longer, Healthier Lives . MIT Press. Bahry, D. (2022 a ). Book review: Methuselah's Zoo by Steven N. Austad. BioEssays [early view]:2200144. https://doi.org/10.1002/bies.202200144 Bahry, D. (2022 b ).Two genes of interest from comparative longevity genomics: FAM126B and OBSCN [preprint]. Zenodo, Sep 14. https://doi.org/10.5281/zenodo.7080278 Finch, CE. (1990). Longevity, Senescence, and the Genome . The University of Chicago Press. 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 Lees, JA. et al. (2017).Architecture of the human ...