Sex differences in pharmacological interventions and their effects on lifespan and healthspan outcomes: a systematic review

Frontiers in Aging

Aging

Marie Knufinke¹  Michael R. MacArthur¹  Collin Y. Ewald²  Sarah J. Mitchell³ 

[1] Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland;[e-mail];null;

关键词: sex differences;    lifespan;    healthspan;    systematic review;    pharmacological interventions;    aging;    mice;   

DOI  :  10.3389/fragi.2023.1172789

 received in 2023-02-23, accepted in 2023-05-10,  发布年份 2023

来源: Frontiers

【 摘 要 】

With an increasing aging population, the burden of age-related diseases magnifies. To alleviate this burden, geroprotection has been an area of intense research focus with the development of pharmacological interventions that target lifespan and/or healthspan. However, there are often sex differences, with compounds mostly tested in male animals. Given the importance of considering both sexes in preclinical research, this neglects potential benefits for the female population, as interventions tested in both sexes often show clear sexual dimorphisms in their biological responses. To further understand the prevalence of sex differences in pharmacological geroprotective intervention studies, we performed a systematic review of the literature according to the PRISMA guidelines. Seventy-two studies met our inclusion criteria and were classified into one of five subclasses: FDA-repurposed drugs, novel small molecules, probiotics, traditional Chinese medicine, and antioxidants, vitamins, or other dietary supplements. Interventions were analyzed for their effects on median and maximal lifespan and healthspan markers, including frailty, muscle function and coordination, cognitive function and learning, metabolism, and cancer. With our systematic review, we found that twenty-two out of sixty-four compounds tested were able to prolong both lifespan and healthspan measures. Focusing on the use of female and male mice, and on comparing their outcomes, we found that 40% of studies only used male mice or did not clarify the sex. Notably, of the 36% of pharmacologic interventions that did use both male and female mice, 73% of these studies showed sex-specific outcomes on healthspan and/or lifespan. These data highlight the importance of studying both sexes in the search for geroprotectors, as the biology of aging is not the same in male and female mice.Systematic Review Registration: [website], identifier [registration number].

【 授权许可】

Unknown   
Copyright © 2023 Knufinke, MacArthur, Ewald and Mitchell.