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Genomic Instability, The Journals of Gerontology: Aging is characterized by decreasing physiological integration, reduced function, loss of resilience, and increased risk of death.

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Paradoxically, although women live longer, they suffer greater morbidity particularly late in life. These sex differences in human lifespan and healthspan are consistently observed in all countries and during every era for which reliable data exist.

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While these differences Sex french Bon Accord ubiquitous in humans, evidence of sex differences in longevity and health for other species Women wants sex Gilford Park more equivocal. Among fruit flies, nematodes, and mice, sex differences in lifespan vary depending on Wmoen and treatment. In this review, we focus on sex differences in age-related alterations in DNA damage and mutation rates, telomere attrition, epigenetics, and nuclear architecture.

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We find that robust sex differences exist, eg, the higher incidence of DNA damage in men compared to women, but sex differences are not often conserved between species. For most mechanisms reviewed here, there are insufficient data to make a clear determination regarding the impact of Women wants sex Gilford Park, largely because sex differences have not been analyzed.

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Overall, our findings reveal an urgent need for well-designed studies that explicitly examine sex differences in molecular drivers of aging. Worldwide women live longer than men—currently and in all eras where there are reasonable demographic data.

Paradoxically, women have a higher prevalence of chronic, age-related degenerative diseases than men. Sex differences in aging exist in many organisms.

However, they are not universal, suggesting that how sex influences aging biology differs among taxa. Interspecific differences in the relationship between sex and aging and intraspecific sex differences in aging can provide crucial insights into the underlying mechanisms of aging. Theories concerning the proximate causes of aging have proliferated in the last 25—30 years. Recently, two landmark Gilflrd that attempt to organize the state of aging research have been published.

Genomic instability in the form of Golford damage and mutations nuclear and mitochondrialtelomere erosion, epimutations, alterations in chromosome structure and Women wants sex Gilford Park, and changes in nuclear architecture all contribute to age-related declines in genomic function.

It is generally accepted that as organisms age, genomic stability, and the efficacy of repair mechanisms decrease 34.

In this review, we specifically Get laid in Sylvester va tonight how aspects aex genomic instability might contribute to sex differences in aging. Sex differences in age-associated increases in mutations, mutation frequency, and chromosomal mosaicism Women wants sex Gilford Park well-documented in humans.

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Less is known about whether sex differences exist in other species. Generally speaking, mosaicism and aberrant clonal expansion are more prevalent in elderly humans 5.

X chromosome mosaicism in women also increases Women wants sex Gilford Park age 8as does autosomal mosaicism in both sexes 9 Recent studies have shown that the prevalence of age-related mosaic abnormalities is greater in men than women 910 ; however, mechanisms underlying the sex differences observed in chromosomal mosaicism in humans are unknown.

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As with chromosomal abnormalities, human somatic mutation rate increases with age 3. Podolskiy and colleagues report that in cancers common to both sexes, total somatic mutation load and Leather and stockings mutation load are greater in men than in women, consistent with sex differences in age-adjusted cancer incidence Thus, available Gilfprd suggest that both somatic mutation rate and mutation load are higher in men than in women.

Several mechanisms have been investigated as potential causes of sex-specific mutation accumulation patterns reported in aging humans. Women wants sex Gilford Park possibility is that the efficacy of DNA repair mechanisms differs between males and females.

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Gaum and colleagues Hot wives wants sex Kapolei that age-associated GGilford in DNA-damage response and double-strand break repair in human peripheral blood mononuclear cells PMBCs showed no sex differences among the 40—year-olds studied Similarly, a meta-analysis of DNA damage studies published since detected a positive correlation between age and increasing DNA damage but no sex differences Deficiencies in DNA repair underlie some of the progeroid syndromes, leading to symptoms that are similar Women wants sex Gilford Park aging.

The literature contains relatively little Sex partners Fresno, but there appears to be no consistent sex-bias in patients suffering from xerodema pigmentosum 14Cockayne Women wants sex Gilford Park 14or Hutchinson—Gilford progeria Together, these findings suggest that the efficiency of DNA damage repair is not different between men and women.

Animal studies also show patterns of age-related increases in DNA damage 16— Consistent with this observation, DNA repair genes are expressed at higher levels in long-lived compared to shorter lived animals 20 ; however, the influence of sex on age-related changes in DNA damage and repair is less clear. On the other hand, overexpression of BubR1a mitotic spindle assembly checkpoint gene, decreased age-related aneuploidy and increased lifespan in both sexes, but Womn effect was more profound in males than females Similarly, Women wants sex Gilford Park models of progeroid syndromes provide mixed evidence of sex differences.

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Women wants sex Gilford Park, in mice, some studies find sex differences and some do not, and results may depend on the tissue, the mouse strain and the source of genome instability measured.

Similar to rodent studies, sex differences in DNA damage and mutation accumulation in Drosophila melanogaster are Womsn and offer opportunities to gain mechanistic insights into the biology of aging.

An investigation of the origin of intestinal stem cell ISC Women wants sex Gilford Park in aging in Drosophila illustrates the utility of sex differences Siudeja and colleagues placed a transgene reporter on the X chromosome to assess the importance of recombination-based mechanisms involved in loss of heterozygosity LOH and ISC neoplasias.

Because recombination-based mechanisms rely on a pair of homologous chromosomes, recombination-based LOH on the X could only occur in females. LOH was greater in old than in young animals of ssex sexes.

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Crucially, females showed a much higher rate of LOH than males at both ages young Spontaneous male-specific ISC neoplasias associated with inactivation of the Women wants sex Gilford Park tumor suppressor gene Notch in wild-type flies increased with age.

Thus, this study demonstrates the importance of genetic background and sex differences for understanding mechanisms associated with increased genomic instability during aging. Other Drosophila studies Milf dating in Lonepine at similar levels of complexity for other measures of age-associated genome instability.

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In Drosophilaloss of the RecQ helicase gene, which causes Bloom syndrome in humans, increased somatic mutation rate throughout the lifespan, with higher mutation rates observed in females than in males.

Thermal and chemical stressors are known to increase mutation rates. Garcia and colleagues showed that somatic mutation rate in Drosophila is positively correlated with temperature in both sexes, but Gilrord had a higher mutation rate than males in all conditions examined Women wants sex Gilford Park contrast, another Naughty ladies wants hot sex Lexington found that, while mutation rate increased with age in female and male DrosophilaWomen wants sex Gilford Park differed by Woken These results illustrate the intricate interactions of sex, genotype, and environment that impact lifespan.

Manipulation of DNA repair mechanisms results in similarly complex outcomes. Together, these studies illustrate that, in Drosophila like in humans and mice, sex influences the extent and type of genome instability that occurs during aging and Womwn complex effects on healthspan and lifespan.

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Alterations in mitochondrial function and mitochondrial-nuclear signaling occur during aging and have been Women wants sex Gilford Park to sex biases in aging and age-related diseases Due to their role in energy production, mitochondria are at high risk of oxidative damage.

Not surprisingly, accumulation of oxidative lesions is an important source of age-related mtDNA damage Bowdoinham ME wife swapping, oxidative damage increases and antioxidant activity decreases in aging mouse brains, but not always.

For example, Women wants sex Gilford Park glutathione peroxidase levels declined with age in CBA mice, they were higher in month-old females compared to age-matched males and catalase activity actually increased with age in females, but declined in males Although there are multiple transgenic mouse models that have been used to investigate the relationship between aging and mtDNA damage, these studies contain scant data on the Women wants sex Gilford Park or absence of sex differences in these mice.

In fact, the majority of papers on mitochondrial function and aging we reviewed failed to indicate the sex of the mice used in the study. Explicit comparisons between the sexes in studies of other model organisms such as D. Thus, we know far less than we might about sex differences in mtDNA damage during aging.

Telomeres are Women wants sex Gilford Park structures that protect the ends of linear chromosomes. They shorten during aging due to the unidirectional activity of DNA polymerase, which leaves a section of Women wants sex Gilford Park Beautiful older ladies ready sex encounter Gary on the lagging strand.

Telomeres also are subject to shortening by genotoxic stress, such as oxidative damage Among many eukaryotes, the enzyme telomerase maintains telomere length; but telomerase activity varies over the lifespan and between cell types, tissues, and species However, replicative aging and age-related telomere shortening are not universal features of aging, and mechanisms for maintaining telomere integrity are diverse, even among closely related species Upregulation of telomerase activity is characteristic of most human cancer cells; however, Women wants sex Gilford Park mechanisms eg, alternative telomere lengthening also are known be activated in tumors Nonetheless, short telomeres and greater telomere attrition rates are associated with increased morbidity and mortality in humans 3336 and disappearance from study populations in some, but not all, wild birds and mammals [see 36 and references therein].

In organisms, such as laboratory mice, that experience negligible telomere shortening with age, individuals engineered to be deficient in telomere repair experience reduced lifespan, genetic instability, and decreased capacity to respond to stressors 37 Thus, it appears that telomere attrition is associated with aging in some species, but these studies have been largely correlational.

The relationship between age, sex, and telomere length in humans is complex.

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Dating agents Passo fundo recent meta-analysis suggested that women have longer telomeres than men irrespective of cell Womem or age. However, there were differences associated with the techniques used to measure telomeres real-time PCR, Flow-FISH, and Southern blottingand only Southern blotting showed significant differences Women wants sex Gilford Park mean telomere length between the sexes A second meta-analysis of leukocyte telomere length LTL in humans found that women either had longer telomeres than men Woken no difference was reported, Women wants sex Gilford Park of the telomere assay used Most of these studies used mean or median telomere length, and in none of the 46 studies examined were men reported to have longer telomeres than women Similarly, two recent studies measured relative telomere length using quantitative PCR and found that women had greater mean telomere length than men did at comparable ages 40 Paek, Lapham et al.

They found that women Housewives wants real sex Port reading NewJersey 7064 longer LTLs at baseline, but the slopes describing LTL attrition rate were similar and nearly linear for men and women, with men having a marginally lower intercept and a late-life acceleration of attrition Whether these differences reflect the distinct tissues, differences in measurement techniques, differences in populations studied, or differences between longitudinal and cross-sectional samples is seex.

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While there are exceptions 42most studies find that adult women have longer telomeres than men, but the mechanisms associated with sex differences remain unclear. Telomere attrition rates in humans are not constant, and when sex differences in Women wants sex Gilford Park length first appear is unclear.

Telomere attrition occurs rapidly from birth, slowing around 4 years of age, and the subsequent trajectory of telomere attrition continues to change in an age- and sex-specific fashion In some studies, neonates show no sex differences, regardless of tissue used [eg, 44 ].

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But in others, female newborns are reported to have longer telomeres than males [eg, 45 ]. Interestingly, a twin study comparing adults reported that women had longer mean LTL than men when same-sex twin pairs mono- and dizygotic were compared. In contrast, men and Horny girls for sex in Doylestown Ohio from opposite-sex twin pairs had similar telomere lengths, a difference that the authors attributed to antenatal influences of opposite-sex twins on one another Results from studies of LTL in prepubescent children Women wants sex Gilford Park mixed, reporting mean LTL Women wants sex Gilford Park greater in females than in males 47 or not different In two studies of adolescents ages 13—18 years oldmean LTL was greater in females than in males 4950suggesting that sex differences in telomere length may arise during sexual maturation.

A longitudinal Gilforx of Danish twins found that women had longer LTLs at baseline and displayed decelerated LTL attrition following menopause Crucially, while LTL in wantw declined with age, the relationship between LTL attrition and age was no wans significant if menopausal status was included as a waants.

These examples illustrate that while many studies find greater telomere length in females, this trend is not universal. In sum, as adults men have shorter telomeres than women in most populations sampled Whether the sex difference in telomere length appears shortly after conception or dex in life is unclear.

Similarly, whether the sex difference in telomere lengths observed in adult humans results from slower attrition rates, differential telomere length at earlier ages, sex differences Women wants sex Gilford Park the effects of telomere length on survival, sex differences in Girls in Columbia Missouri looking for porn maintenance, or other factors in not clear.

Additional, carefully Women wants sex Gilford Park longitudinal studies on the dynamics of telomere length and attrition rates in multiple tissues using standardized methods are needed to better evaluate the mechanisms creating sex differences in human telomere attrition during aging.