Genetic differences and longevity‐related phenotypes influence lifespan and lifespan variation in a sex‐specific manner in mice
Aging Cell, vol. 19, pp. e13263
Abstract
Epidemiological studies of human longevity found two interesting features, robust advantage of female lifespan and consistent reduction of lifespan variation. To help understand the genetic aspects of these phenomena, the current study examined sex differences and variation of longevity using previously published mouse data sets including data on lifespan, age of puberty, and circulating insulin-like growth factor 1 (IGF1) levels in 31 inbred strains, data from colonies of nuclear-receptor-interacting protein 1 (Nrip1) knockout mice, and a congenic strain, B6.C3H-Igf1. Looking at the overall data for all inbred strains, the results show no significant difference in lifespan and lifespan variation between sexes; however, considerable differences were found among and within strains. Across strains, lifespan variations of female and male mice are significantly correlated. Strikingly, between sexes, IGF1 levels correlate with the lifespan variation and maximum lifespan in different directions. Female mice with low IGF1 levels have higher variation and extended maximum lifespan. The opposite is detected in males. Compared to domesticated inbred strains, wild-derived inbred strains have elevated lifespan variation due to increased early deaths in both sexes and extended maximum lifespan in female mice. Intriguingly, the sex differences in survival curves of inbred strains negatively associated with age of female puberty, which is significantly accelerated in domesticated inbred strains compared to wild-derived strains. In conclusion, this study suggests that genetic factors are involved in the regulation of sexual disparities in lifespan and lifespan variation, and dissecting the mouse genome may provide novel insight into the underlying genetic mechanisms.
Authors 8
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Rong Yuan corresponding
Affiliation as printed
Department of Internal Medicine Geriatrics Research Southern Illinois University School of Medicine Springfield IL USA
Department of Internal Medicine, Geriatrics Research, Southern Illinois University School of Medicine, Springfield, IL, USA
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C.J.M. Musters Aachen Institute of Environmental Sciences (CML) Leiden University Leiden The Netherlands Institute of Environmental Sciences (CML)
Affiliation as printed
Institute of Environmental Sciences Leiden University Leiden The Netherlands
Institute of Environmental Sciences, Leiden University, Leiden, The Netherlands
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Affiliation as printed
Department of Internal Medicine Geriatrics Research Southern Illinois University School of Medicine Springfield IL USA
Department of Molecular Biology, Microbiology and Biochemistry Southern Illinois University School of Medicine Springfield IL USA
Department of Internal Medicine, Geriatrics Research, Southern Illinois University School of Medicine, Springfield, IL, USA
Department of Molecular Biology, Microbiology and Biochemistry, Southern Illinois University School of Medicine, Springfield, IL, USA
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Affiliation as printed
Department of Neurology Southern Illinois University School of Medicine Springfield IL USA
Department of Neurology, Southern Illinois University School of Medicine, Springfield, IL, USA
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SIU Medicine · Chinese Academy of Medical Sciences & Peking Union Medical College · Chinese Academy of Medical Sciences Dermatology Hospital
Affiliation as printed
Department of Internal Medicine Geriatrics Research Southern Illinois University School of Medicine Springfield IL USA
Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing China
Department of Internal Medicine, Geriatrics Research, Southern Illinois University School of Medicine, Springfield, IL, USA
Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
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Affiliation as printed
The Jackson Laboratory Nathan Shock Centre of Excellence in the Basic Biology of Aging Bar Harbor ME USA
The Jackson Laboratory Nathan Shock Centre of Excellence in the Basic Biology of Aging, Bar Harbor, ME, USA
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Affiliation as printed
The Jackson Laboratory Nathan Shock Centre of Excellence in the Basic Biology of Aging Bar Harbor ME USA
The Jackson Laboratory Nathan Shock Centre of Excellence in the Basic Biology of Aging, Bar Harbor, ME, USA
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Affiliation as printed
Department of Internal Medicine Geriatrics Research Southern Illinois University School of Medicine Springfield IL USA
Department of Internal Medicine, Geriatrics Research, Southern Illinois University School of Medicine, Springfield, IL, USA
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