title: 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.
authors.affiliation: Interdepartmental Centre "L. Galvani" (CIG) and Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Via San Giacomo 12, 40126 Bologna, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Ostan
authors.affiliation: Department of Clinical and Experimental Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Monti
authors.affiliation: Department of Statistical Sciences "Paolo Fortunati", University of Bologna, Via Belle Arti 41, 40126 Bologna.
authors.forename: Paola
authors.initials: P
authors.lastname: Gueresi
authors.affiliation: Internal Medicine Unit, Department of Molecular Medicine, University of Padua, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Bussolotto
authors.affiliation: IRCCS, Institute of Neurological Sciences of Bologna, 40139 Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.affiliation: Internal Medicine Unit, Department of Molecular Medicine, University of Padua, Italy giovannella.baggio@sanita.padova.it.
authors.forename: Giovannella
authors.initials: G
authors.lastname: Baggio
mesh_terms: D000375:Aging / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D000818:Animals; D005260:Female; D006801:Humans; D008136:Longevity; D008297:Male; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D012737:Sex Factors
keywords: X chromosome inactivation; aging; centenarians; gender; gender-specific medicine; gut microbiome; longevity; mitochondrial DNA