Sex difference in pathology of the ageing gut mediates the greater response of female lifespan to dietary restriction
Jennifer C Regan,
Mobina Khericha,
Adam J Dobson,
Ekin Bolukbasi,
Nattaphong Rattanavirotkul,
Linda Partridge
Affiliations
Jennifer C Regan
Institute of Healthy Ageing, Department of Genetics, Evolution, and Environment, University College London, London, United Kingdom
Mobina Khericha
Institute of Healthy Ageing, Department of Genetics, Evolution, and Environment, University College London, London, United Kingdom
Adam J Dobson
Institute of Healthy Ageing, Department of Genetics, Evolution, and Environment, University College London, London, United Kingdom
Ekin Bolukbasi
Institute of Healthy Ageing, Department of Genetics, Evolution, and Environment, University College London, London, United Kingdom
Nattaphong Rattanavirotkul
Institute of Healthy Ageing, Department of Genetics, Evolution, and Environment, University College London, London, United Kingdom
Linda Partridge
Institute of Healthy Ageing, Department of Genetics, Evolution, and Environment, University College London, London, United Kingdom; Max Planck Institute for Biology of Ageing, Cologne, Germany
Women live on average longer than men but have greater levels of late-life morbidity. We have uncovered a substantial sex difference in the pathology of the aging gut in Drosophila. The intestinal epithelium of the aging female undergoes major deterioration, driven by intestinal stem cell (ISC) division, while lower ISC activity in males associates with delay or absence of pathology, and better barrier function, even at old ages. Males succumb to intestinal challenges to which females are resistant, associated with fewer proliferating ISCs, suggesting a trade-off between highly active repair mechanisms and late-life pathology in females. Dietary restriction reduces gut pathology in aging females, and extends female lifespan more than male. By genetic sex reversal of a specific gut region, we induced female-like aging pathologies in males, associated with decreased lifespan, but also with a greater increase in longevity in response to dietary restriction.
