New discoveries about ageing in C. elegans
David Gems, Alexandre Benedetto, Marina Ezcurra, Ann Gilliat and Yuan Zhao
Institute of Healthy Ageing, University College London
Arguably, C. elegans ageing studies have stalled slightly in recent years. Life span genetics identifies ever more new genes and pathways, yet the proximate mechanisms of ageing that such genes influence remain largely unclear. Recent work in my lab is using new ideas from M.V. Blagosklonny to develop and test novel hypotheses about the primary causes of ageing in C. elegans. These ideas link G.C. Williams’s evolutionary concepts (particularly antagonistic pleiotropy) with recent findings on the role of insulin/IGF-1 signaling in ageing. They suggest that senescent pathologies that limit lifespan may be driven primarily by late life run-on of wild-type gene function, rather than damage accumulation (e.g. due to reactive oxygen species). They motivate a new, pathology-centred approach to understanding senescence, particularly via the study of how pathologies develop ("developmental pathology"), and how they cause mortality. This has enabled the discovery of several new mechanisms by which senescent pathologies originate in C. elegans, including intestinal and gonadal atrophy, yolky pool formation (a form of senescent obesity), and uterine tumours. These mechanisms provide clues to the origins of several senescent pathologies in humans. It has also yielded insights into the causes and mechanisms of organismal death in C. elegans.
David Gems, Alexandre Benedetto, Marina Ezcurra, Ann Gilliat and Yuan Zhao
Institute of Healthy Ageing, University College London
Arguably, C. elegans ageing studies have stalled slightly in recent years. Life span genetics identifies ever more new genes and pathways, yet the proximate mechanisms of ageing that such genes influence remain largely unclear. Recent work in my lab is using new ideas from M.V. Blagosklonny to develop and test novel hypotheses about the primary causes of ageing in C. elegans. These ideas link G.C. Williams’s evolutionary concepts (particularly antagonistic pleiotropy) with recent findings on the role of insulin/IGF-1 signaling in ageing. They suggest that senescent pathologies that limit lifespan may be driven primarily by late life run-on of wild-type gene function, rather than damage accumulation (e.g. due to reactive oxygen species). They motivate a new, pathology-centred approach to understanding senescence, particularly via the study of how pathologies develop ("developmental pathology"), and how they cause mortality. This has enabled the discovery of several new mechanisms by which senescent pathologies originate in C. elegans, including intestinal and gonadal atrophy, yolky pool formation (a form of senescent obesity), and uterine tumours. These mechanisms provide clues to the origins of several senescent pathologies in humans. It has also yielded insights into the causes and mechanisms of organismal death in C. elegans.
