title: Sex Differences in Longevity and in Responses to Anti-Aging Interventions: A Mini-Review.
abstract: A robust, often underappreciated, feature of human biology is that women live longer than men not just in technologically advanced, low-mortality countries such as those in Europe or North America, but across low- and high-mortality countries of the modern world as well as through history. Women's survival advantage is not due to protection from one or a few diseases. Women die at lower rates than men from virtually all the top causes of death with the notable exception of Alzheimer's disease, to which women are particularly prone. Yet, despite this robust survival advantage, women across countries of the world suffer worse health throughout life. The biological mechanisms underlying either longer female survival or poorer female health remain elusive and understudied. Mechanisms of mammalian biology, particularly with respect to aging and disease, are most easily studied in laboratory mice. Although there are no consistent differences in longevity between mouse sexes even within single genotypes, there are often substantial differences in individual studies, sometimes favoring females, other times males. Investigating the environmental causes of this puzzling variation in longevity differences could prove illuminating. Sex differences in response to life-extending genetic or pharmacological interventions appear surprisingly often in mice. Longevity enhancement due to reduced signaling through IGF-1 or mTOR signaling typically favors females, whereas enhancement via a range of pharmacological treatments favors males. These patterns could be due to interactions of the interventions with sex steroids, with adiponectin or leptin levels, or with the sex differences in immune function or the regional distribution of body fat. Clearly, generalizations from one sex cannot be extended to the other, and inclusion of both sexes in biomedical studies of human or other animals is worth the effort and expense.
authors.affiliation: Department of Biology, The University of Alabama at Birmingham, Birmingham, Ala., USA.
authors.forename: Steven N
authors.initials: SN
authors.lastname: Austad
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bartke
mesh_terms: D020909:Acarbose / Q000627:therapeutic use; D000375:Aging / Q000502:physiology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D005260:Female; D065089:Glycoside Hydrolase Inhibitors / Q000627:therapeutic use; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D065089:Glycoside Hydrolase Inhibitors; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D058570:TOR Serine-Threonine Kinases; D001241:Aspirin; D020909:Acarbose