Gender, aging and longevity in humans: an update of an intriguing/neglected scenario paving the way to a gender-specific medicine

Abstract

Data showing a remarkable gender difference in life expectancy and mortality, including survival to extreme age, are reviewed starting from clinical and demographic data and stressing the importance of a comprehensive historical perspective and a gene–environment/lifestyle interaction. Gender difference regarding prevalence and incidence of the most important age-related diseases, such as cardiovascular and neurodegenerative diseases, cancer, Type 2 diabetes, disability, autoimmunity and infections, are reviewed and updated with particular attention to the role of the immune system and immunosenescence. On the whole, gender differences appear to be pervasive and still poorly considered and investigated despite their biomedical relevance. The basic biological mechanisms responsible for gender differences in aging and longevity are quite complex and still poorly understood. The present review focuses on centenarians and their offspring as a model of healthy aging and summarizes available knowledge on three basic biological phenomena, i.e. age-related X chromosome inactivation skewing, gut microbiome changes and maternally inherited mitochondrial DNA genetic variants. In conclusion, an appropriate gender-specific medicine approach is urgently needed and should be systematically pursued in studies on healthy aging, longevity and age-related diseases, in a globalized world characterized by great gender differences which have a high impact on health and diseases.

Undulating changes in human plasma proteome across lifespan are linked to disease

“…1d); 895 proteins out of the 1,379 proteins altered with age (q<0.05) were significantly different between males and females (q<0.05, Supplementary Table 4). These results are aligned with a growing number of studies demonstrating that males and females age differently 19 . To determine whether these findings are representative of the general population, we compared changes identified in this study with findings from 4 small independent cohorts (n=171, age range 21-107y, Supplementary Fig.…”

“…It is well known that men and women age differently 19 , but we were surprised to find that 2/3 of the proteins changing with age are also changing with sex (895 proteins out of the 1,379 proteins changing with age). These results strongly support the National Institutes of Health (NIH) policy on the inclusion of women in clinical research and the inclusion of sex as a biological variable in scientific experiments.…”

Sex differences in cancer mechanisms

“…Worldwide, women live longer than men [265,266], and numerous age-associated diseases-including cardiovascular diseases, neurodegenerative disorders, and cancer-exhibit sex differences in presentation, response to treatment, and mortality [267]. Senescent cells and SASP are important mediators of normal and pathological aging phenotypes.…”

Genetics of Human Longevity Within an Eco-Evolutionary Nature-Nurture Framework

“…It is well known that human longevity -with some exception -is strongly correlated with sex, and that females generally live longer than male, likely because of the combination of biological factors (anatomy, reproductive functions, sex hormones, expression of genes on the X or Y chromosome) and social factors related to behaviour, population and peculiar life experiences [66][67][68] as showed in Figure 4. Gender influences also the inheritance of exceptional longevity 69 .…”