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

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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.

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Global prevalence of diabetes: estimates for the year 2000 and projections for 2030.

Sarah E Wild, Gojka Roglic, Anders Green … (2004)

The goal of this study was to estimate the prevalence of diabetes and the number of people of all ages with diabetes for years 2000 and 2030. Data on diabetes prevalence by age and sex from a limited number of countries were extrapolated to all 191 World Health Organization member states and applied to United Nations' population estimates for 2000 and 2030. Urban and rural populations were considered separately for developing countries. The prevalence of diabetes for all age-groups worldwide was estimated to be 2.8% in 2000 and 4.4% in 2030. The total number of people with diabetes is projected to rise from 171 million in 2000 to 366 million in 2030. The prevalence of diabetes is higher in men than women, but there are more women with diabetes than men. The urban population in developing countries is projected to double between 2000 and 2030. The most important demographic change to diabetes prevalence across the world appears to be the increase in the proportion of people >65 years of age. These findings indicate that the "diabetes epidemic" will continue even if levels of obesity remain constant. Given the increasing prevalence of obesity, it is likely that these figures provide an underestimate of future diabetes prevalence.

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Inflamm-aging. An evolutionary perspective on immunosenescence.

C Franceschi, M BonaFe, S Valensin … (2000)

In this paper we extend the "network theory of aging," and we argue that a global reduction in the capacity to cope with a variety of stressors and a concomitant progressive increase in proinflammatory status are major characteristics of the aging process. This phenomenon, which we will refer to as "inflamm-aging," is provoked by a continuous antigenic load and stress. On the basis of evolutionary studies, we also argue that the immune and the stress responses are equivalent and that antigens are nothing other than particular types of stressors. We also propose to return macrophage to its rightful place as central actor not only in the inflammatory response and immunity, but also in the stress response. The rate of reaching the threshold of proinflammatory status over which diseases/disabilities ensue and the individual capacity to cope with and adapt to stressors are assumed to be complex traits with a genetic component. Finally, we argue that the persistence of inflammatory stimuli over time represents the biologic background (first hit) favoring the susceptibility to age-related diseases/disabilities. A second hit (absence of robust gene variants and/or presence of frail gene variants) is likely necessary to develop overt organ-specific age-related diseases having an inflammatory pathogenesis, such as atherosclerosis, Alzheimer's disease, osteoporosis, and diabetes. Following this perspective, several paradoxes of healthy centenarians (increase of plasma levels of inflammatory cytokines, acute phase proteins, and coagulation factors) are illustrated and explained. In conclusion, the beneficial effects of inflammation devoted to the neutralization of dangerous/harmful agents early in life and in adulthood become detrimental late in life in a period largely not foreseen by evolution, according to the antagonistic pleiotropy theory of aging.

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The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries.

Andrew Ambrosy, Gregg C. Fonarow, Javed Butler … (2014)

Heart failure is a global pandemic affecting an estimated 26 million people worldwide and resulting in more than 1 million hospitalizations annually in both the United States and Europe. Although the outcomes for ambulatory HF patients with a reduced ejection fraction (EF) have improved with the discovery of multiple evidence-based drug and device therapies, hospitalized heart failure (HHF) patients continue to experience unacceptably high post-discharge mortality and readmission rates that have not changed in the last 2 decades. In addition, the proportion of HHF patients classified as having a preserved EF continues to grow and may overtake HF with a reduced EF in the near future. However, the prognosis for HF with a preserved EF is similar and there are currently no available disease-modifying therapies. HHF registries have significantly improved our understanding of this clinical entity and remain an important source of data shaping both public policy and research efforts. The authors review global HHF registries to describe the patient characteristics, management, outcomes and their predictors, quality improvement initiatives, regional differences, and limitations of the available data. Moreover, based on the lessons learned, they also propose a roadmap for the design and conduct of future HHF registries. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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Author and article information

Journal

Journal ID (nlm-ta): Clin Sci (Lond)

Journal ID (iso-abbrev): Clin. Sci

Journal ID (hwp): ppclinsci

Journal ID (publisher-id): CS

Title: Clinical Science (London, England : 1979)

Publisher: Portland Press Ltd.

ISSN (Print): 0143-5221

ISSN (Electronic): 1470-8736

Publication date (Electronic): 23 August 2016

Publication date (Print): 1 October 2016

Volume: 130

Issue: 19 ( displayID: 19 )

Pages: 1711-1725

Affiliations

[* ]Interdepartmental Centre “L. Galvani” (CIG) and Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Via San Giacomo 12, 40126 Bologna, Italy

[† ]Department of Clinical and Experimental Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy

[‡ ]Department of Statistical Sciences “Paolo Fortunati”, University of Bologna, Via Belle Arti 41, 40126 Bologna

[§ ]Internal Medicine Unit, Department of Molecular Medicine, University of Padua, Italy

[║ ]IRCCS, Institute of Neurological Sciences of Bologna, 40139 Bologna, Italy

Author notes

[1]

These authors are equal first authors.

[2]

These authors are equal senior authors.

Correspondence: Professor Giovannella Baggio (email giovannella.baggio@ 123456sanita.padova.it ).

Article

Publisher ID: CS20160004

DOI: 10.1042/CS20160004

PMC ID: 4994139

PubMed ID: 27555614

SO-VID: 734fb5b6-844d-4676-8980-186c91827004

License:

This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution Licence 4.0 (CC BY).

History

Date received : 14 January 2016

Date revision received : 21 June 2016

Date accepted : 27 June 2016

Page count

Figures: 2, Tables: 1, References: 159, Pages: 15

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

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Sex and gender-sensitive medicine

Most cited references 117

Global prevalence of diabetes: estimates for the year 2000 and projections for 2030.

Inflamm-aging. An evolutionary perspective on immunosenescence.

The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries.

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Cited by 89

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