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 s...
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| Format: | Conference Object |
| Language: | English |
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2022
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| Online Access: | https://zenodo.org/record/7090086 https://doi.org/10.5281/zenodo.7090086 |
| Summary: | 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 Austad, SN. (2022). Methuselah's Zoo: What Nature Can Teach Us About Living Longer, Healthier Lives. MIT Press. Bahry, D. (2022a). Book review: Methuselah's Zoo by Steven N. Austad. BioEssays [early view]: 2200144. https://doi.org/10.1002/bies.202200144 Bahry, D. (2022b). 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 ... |
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