Why do sexes differ in lifespan extension? Sex-specific pathways of aging and underlying mechanisms for dimorphic responses

2020 ◽  
Vol 5 (4) ◽  
pp. 247-259 ◽  
Author(s):  
Michael Garratt

Males and females typically have different lifespans and frequently differ in their responses to anti-aging interventions. These sex-specific responses are documented in mice and Drosophila species, in addition to other organisms where interventions have been tested. While the prevalence of sex-specific responses to anti-aging interventions is now recognised, the underlying causes remain poorly understood. This review first summarises the main pathways and interventions that lead to sex-specific lifespan responses, including the growth-hormone/insulin-like growth factor 1 (GH-IGF1) axis, mechanistic target of rapamycin (mTOR) signalling, and nutritional and pharmacological interventions. After summarising current evidence, several different potential causes for sex-specific responses are discussed. These include sex-differences in xenobiotic metabolism, differing disease susceptibility, sex-specific hormone production and chromosomes, and the relative importance of different signalling pathways in the control of male and female life-history. Understanding why sex-differences in lifespan-extension occur should provide a greater understanding of the mechanisms that regulate the aging process in each sex, and will be crucial for understanding the full implications of these treatments if they are translated to humans.

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0240284
Author(s):  
Carolyn R. Hodges-Simeon ◽  
Graham Albert ◽  
George B. Richardson ◽  
Timothy S. McHale ◽  
Seth M. Weinberg ◽  
...  

Sexual selection researchers have traditionally focused on adult sex differences; however, the schedule and pattern of sex-specific ontogeny can provide insights unobtainable from an exclusive focus on adults. Recently, it has been debated whether facial width-to-height ratio (fWHR; bi-zygomatic breadth divided by midface height) is a human secondary sexual characteristic (SSC). Here, we review current evidence, then address this debate using ontogenetic evidence, which has been under-explored in fWHR research. Facial measurements were collected from 3D surface images of males and females aged 3 to 40 (Study 1; US European-descent, n = 2449), and from 2D photographs of males and females aged 7 to 21 (Study 2; Bolivian Tsimane, n = 179), which were used to calculate three fWHR variants (which we call fWHRnasion, fWHRstomion, and fWHRbrow) and two other common facial masculinity ratios (facial width-to-lower-face-height ratio, fWHRlower, and cheekbone prominence). We test whether the observed pattern of facial development exhibits patterns indicative of SSCs, i.e., differential adolescent growth in either male or female facial morphology leading to an adult sex difference. Results showed that only fWHRlower exhibited both adult sex differences as well as the classic pattern of ontogeny for SSCs—greater lower-face growth in male adolescents relative to females. fWHRbrow was significantly wider among both pre- and post-pubertal males in the Bolivian Tsimane sample; post-hoc analyses revealed that the effect was driven by large sex differences in brow height, with females having higher placed brows than males across ages. In both samples, all fWHR measures were inversely associated with age; that is, human facial growth is characterized by greater relative elongation in the mid-face and lower face relative to facial width. This trend continues even into middle adulthood. BMI was also a positive predictor of most of the ratios across ages, with greater BMI associated with wider faces. Researchers collecting data on fWHR should target fWHRlower and fWHRbrow and should control for both age and BMI. Researchers should also compare ratio approaches with multivariate techniques, such as geometric morphometrics, to examine whether the latter have greater utility for understanding the evolution of facial sexual dimorphism.


1974 ◽  
Vol 76 (4) ◽  
pp. 729-740 ◽  
Author(s):  
Peter Kamp ◽  
Per Platz ◽  
Jørn Nerup

ABSTRACT By means of an indirect immunofluorescence technique, sera from 116 patients with Addison's disease, an equal number of age and sex matched controls and 97 patients with other endocrine diseases were examined for the occurrence of antibody to steroid-producing cells in ovary, testis and adrenal cortex. Fluorescent staining was observed in the theca cells of growing follicles, the theca lutein cells, testicular Leydig cells and adrenal cortical cells, i. e. cells which contain enzyme systems used in steroid hormone production. The "steroid-cell" antibody was present in 24 % of the patients with idiopathic Addison's disease, equally frequent in males and females, and in 17 % of the patients with tuberculous Addison's disease, but was rarely found in controls, including patients with other endocrine diseases. Female hypergonadotrophic hypogonadism made an exception, since the "steroid-cell" antibody was found in about half the cases with this condition.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 313-313
Author(s):  
Brianne Olivieri-Mui ◽  
Sandra Shi ◽  
Ellen McCarthy ◽  
Dae Kim

Abstract Frailty may differentially impact how older adult males and females perceive sexual functioning, an important part of well-being. We assessed the level of frailty (robust, pre-frail, frail) for anyone with data on 11 sexual functioning questions asked in wave 2 of the National Social Life, Health, and Aging Project, 2010-2011 (n=2060). Questions covered five domains: overall sexual function (OSF), sexual function anxiety (SFA), changes in sexual function (CSF), erectile/vaginal dysfunction (EVD), and masturbation. Logistic regression identified sex differences in frailty and reporting worse sexual functioning. Linear regression predicted the number of domains reported as worse. Among males (n=1057), pre-frailty meant higher odds of reporting SFA (OR 1.8 95%CI 1.2-6.6), CSF (OR 1.7 95%CI 1.1-2.7), and EVD (OR 1.5 95%CI 1.0-2.2). Among females (n=1003), there was no difference in reporting by frailty. Females were more likely to report worse OSF (Robust: OR 7.4, 95%CI 4.8-11.4; Pre-frail: OR 6.2, 95%CI 3.9-9.9; Frail: OR 3.4 95%CI 1.7-6.6), but less likely to report SFA (Robust OR .3, 95%CI .2-.5; Pre-frail OR .2, 95%CI .1-.3; Frail OR .2 95%CI .1-.3). Pre-frail and frail females reported fewer domains as worse (Pre-frail coefficient -0.21 SE 0.09, Frail -0.43 SE 0.14). As frailty worsened, males reported more domains as worse (Pre-frail 0.24 SE 0.07, Frail 0.29 SE 0.08). Self-reported sexual functioning differs by sex at all levels of frailty, and reporting by males, but not females, changes with frailty. Providers should be aware that sexual functioning is of importance to both sexes despite varying degrees of frailty.


2021 ◽  
pp. svn-2020-000834
Author(s):  
Koteswara Rao Nalamolu ◽  
Bharath Chelluboina ◽  
Casimir A Fornal ◽  
Siva Reddy Challa ◽  
David M Pinson ◽  
...  

Background and purposeThe therapeutic potential of different stem cells for ischaemic stroke treatment is intriguing and somewhat controversial. Recent results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells (MSC) in a rodent stroke model. We hypothesised that MSC treatment would effectively promote the recovery of sensory and motor function in both males and females, despite any apparent sex differences in post stroke brain injury.MethodsTransient focal cerebral ischaemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery. Following the procedure, male and female rats of the untreated group were euthanised 1 day after reperfusion and their brains were used to estimate the resulting infarct volume and tissue swelling. Additional groups of stroke-induced male and female rats were treated with MSC or vehicle and were subsequently subjected to a battery of standard neurological/neurobehavioral tests (Modified Neurological Severity Score assessment, adhesive tape removal, beam walk and rotarod). The tests were administered at regular intervals (at days 1, 3, 5, 7 and 14) after reperfusion to determine the time course of neurological and functional recovery after stroke.ResultsThe infarct volume and extent of swelling of the ischaemic brain were similar in males and females. Despite similar pathological stroke lesions, the clinical manifestations of stroke were more pronounced in males than females, as indicated by the neurological scores and other tests. MSC treatment significantly improved the recovery of sensory and motor function in both sexes, and it demonstrated efficacy in both moderate stroke (females) and severe stroke (males).ConclusionsDespite sex differences in the severity of post stroke outcomes, MSC treatment promoted the recovery of sensory and motor function in male and female rats, suggesting that it may be a promising treatment for stroke.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 8.1-8
Author(s):  
G. Robinson ◽  
K. Waddington ◽  
J. Peng ◽  
A. Radziszewska ◽  
H. Peckham ◽  
...  

Background:Males and females have altered immune responses resulting in variation in autoimmune and cardiovascular disease risk (CVR). Recently, these differences have played a role in the inflammatory response to COVID-19. Sex differences exist in the frequency and activity of immune-cell subsets but mechanisms underlying sexual dimorphism remain unknown. Juvenile-onset systemic lupus erythematosus (JSLE) is an autoimmune disorder that commonly emerges during puberty, has a strong female prevalence (female:male ratio, 4.5:1) and results in an increased CVR. JSLE is characterised by chronic inflammation and dyslipidaemia, where cardiovascular disease is a leading cause of mortality for patients. Our previous work identified a link between immune cell function and lipid metabolism in adult-onset SLE. We hypothesised that sex hormones could influence both lipid metabolism and immune cell function and this could determine sex-specific susceptibility to JSLE and associated CVR.Objectives:We investigated the role of sex hormones in modifying systemic lipid metabolism and inflammation.Methods:Nuclear magnetic resonance spectroscopy based serum metabolomics measuring over 130 lipoproteins (14-subsets with lipid compositions), flow cytometry measuring immune-cells, and RNA-sequencing were used to assess the metabolic and immune profile in young, pre/post-pubertal males (n=10/17) and females (n=10/23) and in individuals with gender-dysphoria (GD) under cross-hormone treatment (trans-male/female, n=26/25). This analysis was also performed on a cohort of post-pubertal male (n=12) and female (n=23) JSLE patients. Data was analysed by logistic regression, balanced random forest machine learning (BRF-ML), differential gene expression (DEG) and pathway analysis.Results:Post-pubertal males had significantly reduced cardio-protective high-density lipoprotein (HDL) subsets (p<0.0001) and increased cardio-pathogenic very-low-density lipoprotein subsets (p<0.0001) compared to females. These differences were not observed pre-puberty and were reversed significantly by cross-hormone treatment in GD individuals, suggesting that sex hormones regulate lipid metabolism in-vivo.BRF-ML (28 immune-cell subsets) identified an increased frequency of anti-inflammatory regulatory T-cells (Tregs) in post-pubertal males compared to females (p=0.0097). These Tregs were also more suppressive in males compared to females. Differences in Treg frequency were seen pre-puberty and were not altered by sex hormone treatment in GD individuals. However, Treg DEGs and functional transcriptomic pathways altered between post-pubertal males and females, including those involved in inflammatory signalling, overlapped with those altered by hormones in GD, suggesting hormones may also drive Treg functional changes. In addition, HDL metabolites modified by hormones showed differential associations with Treg phenotypes between post-pubertal males and females.Strikingly, sex differences in lipoproteins and Tregs were lost in JSLE, suggesting hormone signalling could be dysregulated in the pathogenesis of autoimmunity and could increase CVR for patients.Conclusion:Sex hormones drive altered lipoprotein metabolism and functional transcriptomic pathways in Tregs. Males have a lipoprotein profile associated with increased CVR, but a more anti-inflammatory immune profile compared to females. Together, this could explain sex differences in inflammatory disease susceptibilities and inform future sex-specific therapeutic strategies for the management of both JSLE and CVR.Acknowledgements:Lupus UKRosetrees TrustVersus ArthritisNIHR UCLH Biomedical Research CentreDisclosure of Interests:None declared


2020 ◽  
Vol 6 (1) ◽  
pp. e000965
Author(s):  
Natalie A Lowenstein ◽  
Peter J Ostergaard ◽  
Daniel B Haber ◽  
Kirsten D Garvey ◽  
Elizabeth G Matzkin

ObjectivesRisk factors for anterior shoulder dislocation include young age, contact activities and male sex. The influence of sex on patient-reported outcomes of arthroscopic Bankart repair (ABR) is unclear, with few studies reporting potential differences. This study’s purpose was to compare patient-reported outcomes of males and females following ABR.MethodsProspectively collected data was analysed for 281 patients (males: 206, females: 75) after ABR with preoperative, 1-year and 2-year follow-up responses. The Wilcoxon signed-rank and χ2 tests, preoperative, 1 year and 2 year follow-up results were examined to determine differences of scores in males versus females.ResultsNo statistically significant sex differences were observed in Simple Shoulder Test (SST), American Shoulder and Elbow Surgeons (ASES), Visual Analogue Scale (VAS) or Single Assessment Numerical Evaluation (SANE) Scores at 1-year or 2-year follow-up. Females had lower Veterans RAND 12-item health survey (VR-12) mental health subscores at 2-year follow-up (females: 52.3±9.0, males: 55.8±7.6, p=0.0016). Females were more likely to report that treatment had ‘exceeded expectations’ at 2-year follow-up regarding motion, strength, function and normal sports activities.ConclusionResults of study demonstrate that ABR has similar outcomes for both males and females. There were no statistically significant sex-related differences in SST, ASES, VAS or SANE scores following ABR. VR-12 mental health subscores showed a minimal difference at 2-year follow-up, with lower scores in females.Level of evidenceRetrospective cohort study; level II.


Author(s):  
Felicity Muth ◽  
Amber D Tripodi ◽  
Rene Bonilla ◽  
James P Strange ◽  
Anne S Leonard

Abstract Females and males often face different sources of selection, resulting in dimorphism in morphological, physiological, and even cognitive traits. Sex differences are often studied in respect to spatial cognition, yet the different ecological roles of males and females might shape cognition in multiple ways. For example, in dietary generalist bumblebees (Bombus), the ability to learn associations is critical to female workers, who face informationally rich foraging scenarios as they collect nectar and pollen from thousands of flowers over a period of weeks to months to feed the colony. While male bumblebees likely need to learn associations as well, they only forage for themselves while searching for potential mates. It is thus less clear whether foraging males would benefit from the same associative learning performance as foraging females. In this system, as in others, cognitive performance is typically studied in lab-reared animals under captive conditions, which may not be representative of patterns in the wild. In the first test of sex and species differences in cognition using wild bumblebees, we compared the performance of Bombus vancouverensis nearcticus (formerly bifarius) and Bombus vosnesenskii of both sexes on an associative learning task at Sierra Nevada (CA) field sites. Across both species, we found that males and females did not differ in their ability to learn, although males were slower to respond to the sucrose reward. These results offer the first evidence from natural populations that male bumblebees may be equally as able to learn associations as females, supporting findings from captive colonies of commercial bees. The observed interspecific variation in learning ability opens the door to using the Bombus system to test hypotheses about comparative cognition.


Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Brona Dinneen ◽  
David Heath ◽  
Mohammed Tauseef Ghaffar ◽  
Miriam O'Sullivan ◽  
Carmel Silke ◽  
...  

Abstract Background/Aims  There is currently no consensus regarding sex-related differences in pain intensity and functional abilities among patients with hand osteoarthritis (OA). In this study we determine sex-related differences in pain intensity and functional ability among patients with hand OA, as assessed by a self-report questionnaire and by performance-based tests. Methods  Using the AUSCAN tool for symptom and functional assessment of hand OA with dynamometry we prospectively accessed patients meeting the ACR criteria for hand osteoarthritis. Using this analysis, assessments of pain and function were compared in male and female patients. The outcome measures included self-reported pain measures, functional assessment and dynamometry measures. Results  The study population included 106 patients (90 females and 16 males) with a mean age of males 48.44 (7.48) and females 52.67 (9.43). All patients with symptomatic hand osteoarthritis meeting ACR Criteria. When accessing difference between sexes, men were found to be significantly heavier (p = 0.003) and have greater grip and pinch strength.As part of function and pain assessments there was a significant correlation between difficulty with fine motor skills such as difficulty doing buttons, difficulty when doing jewellery, or peeling vegetables associated with pain when turning objects e.g. doorknobs, taps and faucets for men in comparison to women. Difficulty in these fine motor skills also correlated with stiffness on wakening and pain on lifting heavy objects regardless of sex. A Mann-Whitney U test was run on 106 participants to determine if there were differences in pain or functional scores between males and females. This reviled Median score for males () and females () was statistically significantly different,There were sex differences noted in the correlation associated with pain with rotational movements e.g. turning objects and functional difficulty with fine motor movements including difficulty when doing up buttons ( Males r(14) = -0.109, p = 0.698, Females r(88) =0.489, p = &lt;0.01 value.= ), difficulty when doing jewellery ( Males r(14) =-0.265, p = 0.339.= Females r(88) = 0.570, p = &lt;0.01) , difficulty peeling vegetables ( Males r(14) = -0.207, p = 0.458 Females r(88) = 0.519, &lt;0.01 ) Conclusion  The results demonstrate the presence of sex differences in patients suffering from hand osteoarthritis self-reported functional ability and pain scales. These differences indicate the need for further studies to explore the mechanisms of hand OA and to understanding the specific impact of gender on the development and progression of disease. With further understanding we can obtain the proper strategy to provide better individualised treatment. It also highlights that rehabilitation programs should consider these differences and each patients’ performance limitations in order to address the specific needs of each individual patient. In doing so, improved pain and functional status will improve morbidity in hand OA Disclosure  B. Dinneen: None. D. Heath: None. M. Ghaffar: None. M. O'Sullivan: None. C. Silke: None. B. Whelan: None.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
You Lv ◽  
Xue Zhao ◽  
Weiying Guo ◽  
Ying Gao ◽  
Shuo Yang ◽  
...  

Metabolic diseases, especially diabetes mellitus, have become global health issues. The etiology of diabetes mellitus can be attributed to genetic and/or environmental factors. Current evidence suggests the association of gut microbiota with metabolic diseases. However, the effects of glucose-lowering agents on gut microbiota are poorly understood. Several studies revealed that these agents affect the composition and diversity of gut microbiota and consequently improve glucose metabolism and energy balance. Possible underlying mechanisms include affecting gene expression, lowering levels of inflammatory cytokines, and regulating the production of short-chain fatty acids. In addition, gut microbiota may alleviate adverse effects caused by glucose-lowering agents, and this can be especially beneficial in diabetic patients who experience severe gastrointestinal side effects and have to discontinue these agents. In conclusion, gut microbiota may provide a novel viewpoint for the treatment of patients with diabetes mellitus.


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