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

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.

Influence of fat-free mass and functional status on resting energy expenditure in underweight elders.

BACKGROUND: In underweight elders, resting energy expenditure (REE) and its relationship with fat-free mass (FFM) could be modified by sarcopenia, physical activity, and functional limitation. The aims of this study were to investigate REE and its relationship with quantity and metabolic activity of FFM and to evaluate the influence of functional status on REE in underweight elderly subjects. METHODS: Forty-eight underweight elders (BMI < 20) and 54 normal weight elderly subjects (BMI 20-30) as a control group were selected. Body composition was determined by dual energy x-ray absorptiometry (DEXA). REE was measured by indirect calorimetry. Ability in activities of daily living (ADLs) was assessed by the Katz index. RESULTS: Underweight elders had significantly lower FFM, FFM index (FFM/height(2)), and REE than healthy subjects. REE adjusted for FFM with analysis of covariance remained significantly lower in the underweight group (1287 +/- 85 vs 1715 +/- 139 kcal/day in men, and 1124 +/- 63 vs 1366 +/- 91 kcal/day in women). Katz index in the underweight group was inversely correlated with REE (r = -0.68; p <.001) even after removal of FFM, FM, and gender, by multiple regression analysis. In this model, FFM and Katz index together explained approximately 54% of REE variability. CONCLUSIONS: Underweight elderly subjects show a hypometabolism due to a reduction of both FFM quantity and its metabolic activity. Functional status in ADLs comes out as an important predictor of REE independently from FFM. The limited physical activity might be the underlying determinant of this hypometabolism, but further investigations are necessary to confirm this issue.