Oestradiol reduces the apoptosis of immature B-cells and also increases somatic hypermutation and isotype-switch recombination leading to high-affinity Ig-producing cells. Family studies demonstrated that about 25 % of the variation in human longevity is due to genetic factors. Several hypotheses have been proposed for sex differences in longevity, including more active female immune functioning, the protective effect of estrogen, compensatory effects of the second X chromosome, reduction in the activity of growth hormone and the insulin-like growth factor 1 signaling cascade, and the influence of oxidative stress on a. van Heemst D., Beekman M., Mooijaart S.P., Heijmans B.T., Brandt B.W., Zwaan B.J., Slagboom P.E., Westendorp R.G. Barrett-Connor E.L., Cohn B.A., Wingard D.L., Edelstein SL. ON THIS WEEK'S episode of Have a Nice Future . Raule N., Sevini F., Li S., Barbieri A., Tallaro F., Lomartire L., Vianello D., Montesanto A., Moilanen J.S., Bezrukov V., et al. Leung K.C., Johannsson G., Leong G.M., Ho K.K. Vaccines for the elderly. Failure to consider these differences may also lead to difficulty in precisely defining aging or longevity, a prerequisite to efficient experimental designs. Nonetheless, hundreds if not thousands of publications exist describing research that either directly or indirectly implicate specific genes as being involved in age-related degeneration. Weinberger B., Grubeck-Loebenstein B. In particular, women develop more frequently concentric cardiac hypertrophy with smaller internal cavity and relatively larger wall thickness, preserving a better ejection fraction and myocardial contractility than men. The Xs and Y of immune responses to viral vaccines. Older adults have reduced pathways related to carbohydrate metabolism and amino acid synthesis; however, oldest-old adults exhibited functional differences that distinguished their microbiota from that of young-old adults, such as greater potential for short-chain fatty acid production and increased butyrate derivatives. This trade-off has been developed into a formal theory by Thomas Kirkwood and is known as the Disposable Soma Theory of Aging [15]. Nelson R.L., Dollear T., Freels S., Persky V. The relation of age, race, and gender to the subside location of colorectal carcinoma. X chromosome regulation: diverse patterns in development, tissues and disease. Rapporto Sulla Popolazione: Salute e Sopravvivenza. Gueresi P., Miglio R., Monti D., Mari D., Sansoni P., Caruso C., Bonafede E., Bucci L., Cevenini E., Ostan R., et al. However, lung cancer mortality in American women has increased from 1950 to 1995 by 500% [18]. . Nat Rev Genet. In conclusion, the development of a gender-specific medicine is of the utmost importance in order to complete our understanding of the main mechanisms of aging as well as the differences in prevention, care, treatment, evolution and outcomes of non-communicable diseases in both genders. Another way to approach the longevity differential between women and men is to look at the causes of death across the life span. The .gov means its official. Federal government websites often end in .gov or .mil. Promoting advances in aging biology may allow humanity to break through biological barriers that influence both healthspan and lifespan, allowing for a welcome extension of the period of healthy life, a compression of morbidity, but only a marginal further increase in life expectancy. At the same time, Japan boasts the highest life expectancy in the world - 85 years . 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. After looking at many cultures, and many people who are healthy and have been around for a long time, the way that I define the difference is very simple but profound. Bdard A., Corneau L., Lamarche B., Dodin S., Lemieux S. Sex-related differences in the effects of the Mediterranean diet on glucose and insulin homeostasis. Moreover, findings from different studies conducted in the U.K. and the U.S.A. showed that the greater coronary risk associated with T2D observed in women may reflect a treatment bias that favours men. When a mutation of one of the genes of the X chromosome occurs, females have a second X to compensate, whereas all genes of the unique X chromosome of males express themselves, even if they are. The decline in old-age mortality is thought to be the main cause of the dramatic increase in centenarians [129], whose number doubles approximately every 7years. Interventions to slow aging in humans: are we ready? Thus there is an urgent need to consider the role of gender background in the GM ecology and its relationship with autoimmunity disease onset and therapy effects. Moreover, the error becomes greater with advancing age, suggesting that nutritional recommendations based on the current scientific rationale, i.e., genetic determinism, are even less accurate for the oldest age groups. The human LE 0 has doubled during over an evolutionary span of about 300,000 generations from a great ape ancestor shared with chimpanzees (1, 2). The nutrition researcher may find this statement difficult to accept given the overwhelming successes that nutrition interventions had on infant and childhood health. These investigations suggest that undernutrition in utero leads to higher incidences of adult-onset obesity, hypertension, cardiovascular disease, and type II diabetes [20]. The negative effect of the APOE (apolipoprotein E) 4 allele, one of the most established genetic risk factors for AD, may explain, at least in part, this gender gap. Jakubowicz D., Barnea M., Wainstein J., Froy O. In particular, death rates for IHD (ischaemic heart disease) and stroke are higher for men than for women [10]. Most research in this area has focused on the relationship between fetal/maternal nutrition and adult-onset obesity. This can determine a sexual dimorphism in the immune response in humans [68]. Evidence for an interaction between apolipoprotein E genotype, gender, and Alzheimer disease. The main risk factor for AD is age, and the fact that the majority of AD patients are females has been attributed to longer life expectancy. Received 2016 Jan 14; Revised 2016 Jun 21; Accepted 2016 Jun 27. Based on his mathematical models, several laboratories using artificial selection methods to approximate evolution have supported Hamiltons theories on the evolution of longevity [11,12,13]. The differences between aging and longevity became clearer with the mathematical descriptions by W.D. Hamiltons mathematical theory on longevity was a monumental breakthrough in the understanding of how life span, not aging, evolved. Results show that there were significant differences between urban and rural areas for provision of HCBS. With larger studies surveying the DNA sequences and gene regulation will capture more of the genetic variation between individuals and help identify the mechanisms of the effect of these genetic variations. On the other hand, a number of studies have investigated the association between mtDNA inherited variants and multifactorial diseases, such as diabetes [152], ischaemic disease [153] and neurodegenerative diseases such as PD [154] and AD [44]. A possible explanation for this gender-associated healthsurvival paradox may be found in a higher female sensibility to physical discomfort that led the women to seek medical attention more frequently. Therefore the study of centenarians represents a sort of historical probing that allows the tracing of the above-mentioned complex basis of the longevity today. Others propose that there are biologically based limits to the duration of life, and those limits are being approached now. Beltrn-Snchez H., Finch C.E., Crimmins E.M. Twentieth century surge of excess adult male mortality. Lifespan and longevity are complex and multifactorial traits resulting from an intriguing combination of Nature and nurture, the unique reciprocal interaction between environmental, genetic, epigenetic and stochastic factors, each contributing to the overall phenotype [1,2]. It is worth mentioning that in a mountainous zone of Sardinia (Nuoro province), an exceptionally high number of male centenarians was identified, together with an unusually low F/M ratio [134]. Evidence has suggested that the development of lung cancer is different in women in comparison with men. Androgens polarize nave CD4+ T-cellstowardstheTh1subset and activate CD8+ T-cells; conversely, oestrogens stimulate Th2 responses and activate antibody production [74]. Careers, Unable to load your collection due to an error. Santoro A., Balbi V., Balducci E., Pirazzini C., Rosini F., Tavano F., Achilli A., Siviero P., Minicuci N., Bellavista E., et al. Yasui T., Maegawa M., Tomita J., Miyatani Y., Yamada M., Uemura H., Matsuzaki T., Kuwahara A., Kamada M., Tsuchiya N., et al. Bachman D.L., Wolf P.A., Linn R., Knoefel J.E., Cobb J., Belanger A., D'Agostino R.B., White L.R. Death rates for IHD are 70% higher for men than for women on average in all EU countries [10]. The short answer is that immune resilience, longevity, and better health outcomes tracked together well. In all EU countries, women reported a poorer self-perceived health, more long-standing illnesses and/or more health problems than men [10]. To this end, a brief review will be presented of evolutionary and genetic findings showing that aging lacks genetic determinism whereas longevity evolved. In an effort to improve the health of older Americans through dietary recommendations, the Committee on the Dietary Reference Intakes (CDRI) has added two age classifications, 5170 and 70+. The subsequent reduction of the gender gap can be attributed partly to the narrowing of differences in risk behaviours between males and females, along with the decline in mortality rates from CVD among men [10]. In addition, women showed a delayed onset of IHD (710years on average) in several western EU states, even though, due to harmful lifestyle modifications, the prevalence of IHD is increasing in young women [17]. However, sex hormones seem to influence . Actually, the higher prevalence and severity of arthritis and musculoskeletal disease among older women widely contributes to their worse health and functional status. Gonzalez D.A., Diaz B.B., Rodriguez Perez Mdel C., Hernandez A.G., Chico B.N., de Leon A.C. Austad S.N. Given that the mitochondrial genome (mtDNA) codes for polypeptides that are essential components of the respiratory chain, a number of studies have investigated the association between mtDNA-inherited variants and AD. As such, the principle of genetic determinism provides an appropriate underlying theory for research designs evaluating nutritional factors involved with life span. DOI: 10.1093/gerona/glz098. ), and by Progetto di Ricerca Sanitaria Finalizzata Veneto Region, Italy. Taking advantage of the complete sequencing of a high number of mtDNA molecules, it was also possible to evaluate for the first time the cumulative effect of specific and concomitant mtDNA mutations, including those that have a low or very low impact. Heron M. Deaths: leading causes for 2013. Sex and gender differences in non-small cell lung cancer. (90 Mb difference between species) (82 . In cells from females, one of the two X chromosomes is epigenetically and randomly inactivated in early embryonic life. A first obvious effect of having sex chromosomes is that males have one X and are hemizygous for that chromosome while females have two Xs. While the term lifespan refers to the maximum number of years an individual can live, life expectancy refers to an estimate or an average number of years a person can expect to live. the presence in the same cell of wild-type and mutated mtDNA molecules, has been supposed to have a double role, fuelling mitochondrial dysfunction and, at the same time, functioning as a reservoir of genetic variability helping the cells to cope with environmental and physiological stressors during life [149,150]. Federal government websites often end in .gov or .mil. Recently, a link between Parkinsons and Alzheimers Disease and a toxic gestational environment during neurodevelopment has begun to emerge [21]. Finally, some pregnancy-associated conditions, such as pre-eclampsia and other hypertensive disorders, further contribute to increased risk for future chronic hypertension, CVD, cerebrovascular diseases and death in women [24]. In this commentary, we discuss the difference between aging and longevity and why knowing this difference is important to nutrition research. Moon J.R., Kondo N., Glymour M.M., Subramanian S.V. The https:// ensures that you are connecting to the The composition of vaginal tract microbiota of the mother, the mode of delivery (natural or Caesarean) and breast or formula feeding have a deep impact on the GM of human offspring since the very beginning of life. That is, he used the terms aging and longevity interchangeably even though his theoretical models focused exclusively on longevity. Refocusing nutrition and aging research to be consistent with the current understanding of the cause of aging may not be as difficult as it first may appear. The results have shown an improvement in lipid profile, cardiovascular risk and inflammation markers which was significant in both genders [118,119]. Currently, prostate cancer has become the most common cancer among men after skin cancer in the majority of EU countries, particularly among men aged 65years and over. Sex hormones and the immune response in humans. Ossewaarde M.E., Bots M.L., Verbeek A.L., Peeters P.H., van der Graaf Y., Grobbee D.E., van der Schouw Y.T. However, increases in longevity have not been equally distributed among all subgroups of the population. Several hundreds of individual bacterial species colonize mouth, upper airways, skin, vagina and intestinal tract constituting a complex and dynamic ecosystem which cross-talk with the environment as well as the rest of the body, including liver and brain among others. In: Salvini S., editor. 1, 576578. Sansoni P., Vescovini R., Fagnoni F., Biasini C., Zann,i F., Zanlari L., Telera A., Lucchini G., Passeri G., Monti D., Franceschi C., Passeri M. The immune system in extreme longevity. Another aspect deserving particular attention in the study of female longevity is the complex and contradictory role of mtDNA variability. Indeed, mortality rates at older ages showed a linear downward trend between 1950 and 2012 [128]. Ozcelik T. X chromosome inactivation and female predisposition to autoimmunity. Androgens induce prostate cancer cell proliferation through mammalian target of rapamycin activation and post-transcriptional increases in cyclin D proteins. Kenyon C. The plasticity of aging: Insights from long-lived mutants. Also important are health behavioral risk factors such as smoking and obesity, which are also influenced by gene-environment interactions. Evidence for sexual . The epidemiological data suggest that the rate of aging and age-related disease may decrease in populations consuming foods high in antioxidants [16,17]. In particular, the relative risk for mortality due to coronary heart disease in diabetic patients is 50% higher in women than in men, suggesting that T2D may induce a more unfavourable cardiovascular risk profile among women. Nutritional antioxidants prevent damage to the cell in vitro and the accumulation of cellular damage has found wide acceptance as a proximal cause of organism aging. Regan J.C., Partridge L. Gender and longevity: why do men die earlier than women? the contents by NLM or the National Institutes of Health. Gender difference regarding prevalence and incidence of the most important age-related diseases, such as cardiovascular and neurodegenerative diseases, cancer, Type2 diabetes, disability, autoimmunity and infections, are reviewed and updated with particular attention to the role of the immune system and immunosenescence. We must focus our attention on the time in the life span in which genetic determinism has the greatest influence on random aging outcomes, i.e., the development, juvenile, and reproductively-active periods. Different studies have observed that female APOE 4 carriers show a higher risk of AD compared with males [41,42]. Persell S.D., Baker D.W. Aspirin use among adults with diabetes: recent trends and emerging sex disparities. Salminen A., Ojala J., Kaarniranta K., Kauppinen A. Mitochondrial dysfunction and oxidative stress activate inflammasomes: impact on the aging process and age-related diseases. Therefore IF may be considered as an alternative and more feasible practice than DR to reduce disease risk [116]. A debate about the future course of life expectancy has been ongoing for the last quarter-century. An obvious difference between men and women are the sex chromosomes, which could impact aging and longevity in a number of ways. CRC in women more frequently expresses microsatellite instability showing a lower sensitivity to fluoropyrimidines, cornerstone drugs for the treatment of colorectal carcinoma [35]. This consideration is reinforced by the fact that the importance of GM in human aging is dramatically emerging. However, his theory on aging contained a significant flaw that has been perpetuated in research designs for over 50 years. Schiebinger L. Scientific research must take gender into account. The aging process more closely reflects chance events that affect biological systems during development or during the early reproductively-active years [3]. HHS Vulnerability Disclosure, Help After following the surviving Crimson men for nearly 80 years . Garagnani P., Pirazzini C., Giuliani C., Candela M., Brigidi P., Sevini F., Luiselli D., Bacalini M.G., Salvioli S., Capri M., et al. Wang Q., Santizo R., Baughman V.L., Pelligrino D.A., Iadecola C. Estrogen provides neuroprotection in transient forebrain ischemia through perfusion-independent mechanisms in rats. Aging could not have evolved through natural selection. Owing to their longer life expectancy and the tendency to marry older men, women are more likely to become widows. I. Creative Commons Attribution Licence 4.0 (CC BY), http://ec.europa.eu/eurostat/statistics-explained/index.php/Mortality_and_life_expectancy_statistics, http://www.cancer.gov/research/progress/snapshots/breast. CRC (colorectal cancer) is the second leading cause of cancer death in both genders; in women it occurs 5years later than in men. Gabelli C., Codemo A. Shaw A.C., Panda A., Joshi S.R., Qian F., Allore H.G., Montgomery R.R. Altamirano F., Oyarce C., Silva P., Toyos M., Wilson C., Lavandero S., Uhln P., Estrada M. Testosterone induces cardiomyocyte hypertrophy through mammalian target of rapamycin complex 1 pathway. National Library of Medicine Gagnon A., Smith K.R., Tremblay M., Vzina H., Par P.P., Desjardins B. Our group has shown that female centenarians have a different composition of the GM in comparison with sex-matched younger persons, which is associated with an increase in inflammaging (high plasma levels of pro-inflammatory cytokines such as IL-6 and IL-8). Hamilton [1] and later by B. Charlesworth [10]. Cevenini E., Monti D., Franceschi C. Inflamm-ageing. Although advances in public health beginning in the 19th century initiated the rise in life expectancy, recent gains have been achieved by reducing death rates at middle and older ages. Mitochondria hyperfusion and elevated autophagic activity are key mechanisms for cellular bioenergetic preservation in centenarians. What's marital status got to do with it? Gender inequalities in economic resources, health and functional abilities among older adults. Several studies have suggested that ovarian sex steroid loss favours immunosenescence by contributing to the remodelling of the immune system. The knowledge of the biology of gender differences in humans are still in their infancy and there is an urgent need for specifically targeted large studies across countries, to take into account the above-mentioned cultural and anthropological differences in a globalized world where migration of persons from countries characterized by different genetic, cultural and anthropological traits and habits is a hot topic. Mitochondrial DNA haplogroups and subhaplogroups are associated with Parkinson's disease risk in a Polish PD cohort. The co-occurrence of mtDNA mutations on different oxidative phosphorylation subunits, not detected by haplogroup analysis, affects human longevity and is population specific. Dog breeds differ in pain sensitivity, but these differences don't always match up with the beliefs people -- including veterinarians -- hold about breed-specific pain sensitivity. In: Fritzell J., Lundberg O., editors. Scholz J.L., Diaz A., Riley R.L., Cancro M.P., Frasca D. A comparative review of aging and B cell function in mice and humans. Genetic and epigenetic regulation of human aging and longevity. The role of partnership status on late-life physical function. It is important to underline that women pay for their survival advantage with a worse quality of life in their old age due to an increased prevalence of a variety of disabling non-lethal pathological conditions [15]. The survival advantage of women is counterbalanced by a worse quality of life in advanced age due to the increase in disability and degenerative diseases [12]. AD can be caused by defects in mitochondrial oxidative phosphorylation. However, data on the remodelling of the GM and its association with inflammaging are still lacking in men, underlining again the importance of conducting gender-specific studies to fill this gap. PMID: 31690828. Table 1 reports mortality data by sex regarding the 14 leading causes of death in U.S.A. in 2013 and refers to all races and ages [14]. Data from primary culture of fibroblasts from long-living individuals, including female centenarians, indicate that longevity is characterized by a preserved bioenergetics function probably attained by a successful mitochondria remodelling that can compensate for functional defects through an increase in mass, i.e. Diabetic women have significantly higher levels of blood pressure and lipids than men with diabetes [27]. Nutrients. The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. Populations of Drosophila selected in the laboratory for their timing of reproduction showed that late-life reproducers do indeed live significantly longer than flies having their highest rate of reproduction early in the life span (Figure 2). Widowhood and mortality: a meta-analysis. Centenarians' offspring as a model of healthy aging: a reappraisal of the data on Italian subjects and a comprehensive overview. Careers, Unable to load your collection due to an error. Solana R., Tarazona R., Gayoso I., Lesur O., Dupuis G., Fulop T. Innate immunosenescence: effect of aging on cells and receptors of the innate immune system in humans. Because of their healthy habits, these older adults are less likely to develop age-related chronic diseases, such as high blood pressure, heart disease, cancer, and diabetes, than their same-age peers. Life expectancy and healthy life expectancy at birth. Centenarians, mainly females, present markers of inflammation [e.g. Hamilton W.D. This divergence in life expectancy can partly be explained by the declining rates in maternal mortality; however, a major contribution is due to differences in behaviour and biology between males and females [8]. Indeed, the development and functioning of the central nervous system is strongly influenced by gender. While life expectancy after the age of 70 continues to increase, so too do the number of individuals living with age-related chronic conditions that affect daily activities. Jagger C., Gillies C., Moscone F., Cambois E., Van Oyen H., Nusselder W., Robine J.-M. Inequalities in healthy life years in the 25 countries of the European Union in 2005: a cross-national meta-regression analysis. In particular, central adiposity tends to be more pronounced in post-menopausal women than in men playing a determinant role in the increase in CVD risk. However, in humans, this practice remains difficult, if not impossible, to sustain because it envisages unrealistic levels of self-deprivation, can impair reproductive function and libido, resistance to infection and wound healing, and can increase the risk of osteoporosis and fractures, anaemia and cardiac arrhythmias [101]. The analysis of the mutations occurring in different OXPHOS complexes showed a complex scenario with a different mutation burden in nonagenarian persons compared with controls. Knowing the difference between aging and longevity will be fundamental to developing the strongest designs for nutrition research aimed at establishing recommendations and improving the health of the older population. Immunosenescence is a multifaceted phenomenon that increases morbidity and mortality due to infections and age-related pathologies, and is characterized by changes in innate and adaptive immune responses to foreign antigens [84,85]. Heart failure in women: insights from the Framingham Heart Study.
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