Sex Differences in Lifespan

Austad, Steven N.; Fischer, Kathleen E.

doi:10.1016/j.cmet.2016.05.019

Cited by 397 publications

(368 citation statements)

References 102 publications

(108 reference statements)

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“…A recent review highlighted differences in lifespan of wild-type male and female mice (Austad and Fischer 2016). In our study, male control mice lived ∼10% longer than control female mice.…”

Section: Discussionmentioning

confidence: 65%

IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan

et al. 2017

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Reduced circulating levels of IGF-1 have been proposed as a conserved anti-aging mechanism that contributes to increased lifespan in diverse experimental models. However, IGF-1 has also been shown to be essential for normal development and the maintenance of tissue function late into the lifespan. These disparate findings suggest that IGF-1 may be a pleiotropic modulator of health and aging, as reductions in IGF-1 may be beneficial for one aspect of aging, but detrimental for another. We postulated that the effects of IGF-1 on tissue health and function in advanced age are dependent on the tissue, the sex of the animal, and the age at which IGF-1 is manipulated. In this study, we examined how alterations in IGF-1 levels at multiple stages of development and aging influence overall lifespan, healthspan, and pathology. Specifically, we investigated the effects of perinatal, post-pubertal, and late-adult onset IGF-1 deficiency using genetic and viral approaches in both male and female igf f/f C57Bl/6 mice. Our results support the concept that IGF-1 levels early during lifespan establish the conditions necessary for subsequent healthspan and pathological changes that contribute to aging. Nevertheless, these changes are specific for each sex and tissue. Importantly, late-life IGF-1 deficiency (a time point relevant for human studies) reduces cancer risk but does not increase lifespan. Overall, our results indicate that the levels of IGF-1 during development influence late-life pathology, suggesting that IGF-1 is a developmental driver of healthspan, pathology, and lifespan.

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Section: Discussionmentioning

confidence: 65%

IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan

et al. 2017

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“…Furthermore, we tested whether child’s epigenetic GA at birth predicted early childhood psychiatric problems, and whether child’s epigenetic GA mediated the associations of maternal antenatal depression with child psychiatric problems. Finally, we tested whether the associations were moderated by child’s sex, as sex biases exist in longevity and aging trajectories, 12 epigenetic age based on the Horvath and the Hannum epigenetic age predictors, 6,9 epigenetic GA at birth, 11 and prevalence and etiology of psychiatric problems. 1,3–5,13 .…”

mentioning

confidence: 99%

The Epigenetic Clock at Birth: Associations With Maternal Antenatal Depression and Child Psychiatric Problems

Suarez

Lahti

Czamara

et al. 2018

Journal of the American Academy of Child & Adolescent Psych

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Objective: Maternal antenatal depression may compromise the fetal developmental milieu and contribute to individual differences in aging and disease trajectories in later life. We evaluated the association between maternal antenatal depression and a novel biomarker of aging at birth, namely epigenetic gestational age (GA) based on fetal cord blood methylation data. We also examined whether this biomarker prospectively predicts and mediates maternal effects on early childhood psychiatric problems. Method: A total of 694 mothers from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) Study provided information on history of depression diagnosed before pregnancy; 581 completed the Center for Epidemiological Studies Depression Scale throughout pregnancy, and 407 completed the Child Behavior Checklist at child’s age 3.7 years (SD = 0.75 year). DNA methylation (DNAm) GA of fetal cord blood DNA was based on the methylation profile of 148 selected cytosine linked to guanine by phosphate (CpG) sites. Epigenetic GA was calculated as the arithmetic difference between DNAm GA and chronological GA and adjusted for chronological GA. Results: Maternal history of depression diagnosed before pregnancy (mean difference = –0.25 SD units, 95% CI = –0.46 to 0.03) and greater antenatal depressive symptoms (–0.08 SD unit per 1-SD unit increase, 95% CI = –0.16 to –0.004) were associated with child’s lower epigenetic GA. Child’s lower epigenetic GA, in turn, prospectively predicted total and internalizing problems and partially mediated the effects of maternal antenatal depression on internalizing problems in boys. Conclusion: Maternal antenatal depression is associated with lower epigenetic GA in offspring. This lower epigenetic GA seems to be associated with a developmental disadvantage for boys, who, in early childhood, show greater psychiatric problems.

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“…201 However, differences in lifespan between men and women suggest a putative role of sex hormones on longevity. 202 What we know is that lifespan was not different between singers castrated before puberty and non-castrated singers, suggesting that T does not influence longevity. 203 T, probably might protect centrally from the effects of stress by mitigating the central cascade of events induced by the exposure to stress, while women are more exposed the negative effect of stress.…”

Section: Unresolved Issuesmentioning

confidence: 99%

“…204 How much gender differences in the exposure to sex steroids at any age are involved in determining longevity and the response to stress remains to be established in detail. 202,204 …”

Section: Unresolved Issuesmentioning

confidence: 99%

Aging and sex hormones in males

2016

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Several large cohort studies have disclosed the trajectories of sex steroids changes overtime in men and their clinical significance. In men the slow, physiological decline of serum testosterone (T) with advancing age overlaps with the clinical condition of overt, pathological hypogonadism. In addition, the increasing number of comorbidities, together with the high prevalence of chronic diseases, all further contribute to the decrease of serum T concentrations in the aging male. For all these reasons both the diagnosis of late-onset hypogonadism (LOH) in men and the decision about starting or not T replacement treatment remain challenging. At present, the biochemical finding of T deficiency alone is not sufficient for diagnosing hypogonadism in older men. Coupling hypogonadal symptoms with documented low serum T represents the best strategy to refine the diagnosis of hypogonadism in older men and to avoid unnecessary treatments.

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Sex Differences in Lifespan

Cited by 397 publications

References 102 publications

IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan

IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan

The Epigenetic Clock at Birth: Associations With Maternal Antenatal Depression and Child Psychiatric Problems

Aging and sex hormones in males

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