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• Research Paper Volume 13, Issue 3 pp 3483-3500

  Estradiol is significantly associated with prognosis in non-surgical liver cancer patients: from bench to bedside

  Relevance score: 6.244263

  Rangrang Wang, Yuan Liu, Hongze Sun, Tao Wang, Changcan Li, Junwei Fan, Zhaowen Wang

  Keywords: liver cancer, non-surgical, estradiol, gender, SEER

  Published in Aging on January 10, 2021

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  There are rarely systematic studies to analyze the prognostic factors among non-surgical liver cancer patients. Whether there is a gender difference in the survival of non-surgical liver cancer patients and what may cause this difference is still unclear.

  A total of 12,312 non-surgical liver cancer patients were enrolled in this study. Age, race, sex, grade, tumor TNM stage, marital status, tumor size, and histological type were independent risk factors in liver cancer and were confirmed in the validation cohort. Before menopause, females demonstrated a better mean survival probability than males (39.4±1.4 vs. 32.7±0.8 months, respectively; p<0.001), and continued in post-menopause. The results of differentially expressed genes (DEGs) and KEGG pathway analysis showed that there were significant differences in steroid hormone biosynthesis between male and female liver cancer patients. In vitro experiments revealed that estradiol inhibited the proliferation of hepatocellular cancer cell lines and increased apoptosis, but estrone exerted no effect.

  In conclusion, gender differences in prognosis among non-surgical liver cancer patients were confirmed and attributable primarily to estradiol.

• Research Paper Volume 12, Issue 24 pp 24721-24733

  Age and gender related differences in load-strain response in C57Bl/6 mice

  Relevance score: 5.6790442

  Hammad Mumtaz, Nuria Lara-Castillo, JoAnna M. Scott, Mark Begonia, Mark Dallas, Mark L. Johnson, Thiagarajan Ganesh

  Keywords: C57Bl/6, aging, digital image correlation, gender, mechanical loading

  Published in Aging on December 17, 2020

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  We examined the changes in mechanical strain response of male and female mouse tibia and ulna, using axial compression tests, to assess age-related changes in tibiae and ulnae by a non-contact strain measurement technique called the digital image correlation (DIC) and the standard strain gage. A unique aspect of the study was to compare bones from the same animal to study variations in behavior with aging. This study was conducted using male and female C57Bl/6 mice at 6, 12 and 22 months of age (N=6-7 per age and sex) using three load levels. The DIC technique was able to detect a greater number of statistically significant differences in comparison to the strain gaging method. Male ulna showed significantly higher DIC strains compared to strains captured from strain gage at all three levels of load at 6 months and in the lowest load at 12 months. DIC measurements revealed that the ulna becomes stiffer with aging for both males and females, which resulted in 0.4 to 0.8 times reduced strains in the 22-month group compared to the 6 month group. Male tibia showed three-fold increased strains in the 22 months group at 11.5 N load compared to 6 months group (p<.05).

• Research Paper Volume 12, Issue 21 pp 21613-21637

  Age- and gender-specific characteristics of the resting-state brain activity: a magnetoencephalography study

  Relevance score: 5.6687427

  Hideyuki Hoshi, Yoshihito Shigihara

  Keywords: gender difference, magnetoencephalography (MEG), normative study, oscillations, resting-state activity

  Published in Aging on November 4, 2020

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  Aging and gender influence regional brain activities. Although these biases should be considered during the clinical examinations using magnetoencephalography, they have yet to be standardized. In the present study, resting-state magnetoencephalography data were recorded from 54 healthy females and 48 males aged 22 to 75 years, who were controlled for cognitive performance. The regional oscillatory power was estimated for each frequency band (delta, theta, alpha, beta, low-gamma, and high-gamma) using the sLORETA-like algorithm and the biases of age and gender were evaluated, respectively. The results showed that faster oscillatory powers increased with age in the rostral regions and decreased in the caudal regions, while few slower oscillatory powers changed with age. Gender differences in oscillatory powers were found in a broad frequency range, mostly in the caudal brain regions. The present study characterized the effects of healthy aging and gender asymmetricity on the regional resting-state brain activity, with the aim to facilitate the accurate and efficient use of magnetoencephalography in clinical practice.

• Research Paper Volume 12, Issue 20 pp 19979-20000

  Interplay between gonadal hormones and postnatal overfeeding in defining sex-dependent differences in gut microbiota architecture

  Relevance score: 6.244263

  Jose A. Santos-Marcos, Alexia Barroso, Oriol A. Rangel-Zuñiga, Cecilia Perdices-Lopez, Carmen Haro, Miguel A. Sanchez-Garrido, Helena Molina-Abril, Claes Ohlsson, Pablo Perez-Martinez, Matti Poutanen, Jose Lopez-Miranda, Francisco Perez-Jimenez, Manuel Tena-Sempere, Antonio Camargo

  Keywords: gut microbiota, sex steroids, gender, metabolism, miRNAs

  Published in Aging on October 27, 2020

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  Aging is associated with a decline in sex hormones, variable between sexes, that has an impact on many different body systems and might contribute to age-related disease progression. We aimed to characterize the sex differences in gut microbiota, and to explore the impact of depletion of gonadal hormones, alone or combined with postnatal overfeeding, in rats. Many of the differences in the gut microbiota between sexes persisted after gonadectomy, but removal of gonadal hormones shaped several gut microbiota features towards a more deleterious profile, the effect being greater in females than in males, mainly when animals were concurrently overfed. Moreover, we identified several intestinal miRNAs as potential mediators of the impact of changes in gut microbiota on host organism physiology. Our study points out that gonadal hormones contribute to defining sex-dependent differences of gut microbiota, and discloses a potential role of gonadal hormones in shaping gut microbiota, as consequence of the interaction between sex and nutrition. Our data suggest that the changes in gut microbiota, observed in conditions of sex hormone decline, as those caused by ageing in men and menopause in women, might exert different effects on the host organism, which are putatively mediated by gut microbiota-intestinal miRNA cross-talk.

• Research Paper Volume 12, Issue 18 pp 18251-18273

  Transcriptomic analysis reveals gender differences in gene expression profiling of the hypothalamus of rhesus macaque with aging

  Relevance score: 5.9485407

  Yong Fan, Congru Li, Wendi Pei, Tao Tan, Rong Li, Jie Qiao, Yang Yu

  Keywords: reproductive aging, hypothalamus, transcriptome, gender difference, housekeeping gene

  Published in Aging on September 27, 2020

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  Due to the current delay in childbearing, the importance of elucidating the underlying mechanisms for reproductive aging has increased. Human fertility is considered to be controlled by hormones secreted by the hypothalamic-pituitary-gonadal axis. To clarify the changes in hypothalamic gene expression with increasing age, we performed paired-end strand-specific total RNA sequencing for the hypothalamus tissues of rhesus. We found that hypothalamic gene expression in females was more susceptible to aging than that in males, and reproductive aging in females and males might have different regulatory mechanisms. Intriguingly, the expression of most of the hormones secreted by hypothalamus showed no significant difference among the macaques grouped by age and gender. Moreover, the age-related housekeeping genes in females were enriched in neurodegenerative disorders- and metabolic-related pathways. This study provides evidence that aging may influence hypothalamic gene expression through different mechanisms in females and males and may involve some nonhormonal pathways, which helps further elucidate the process of reproductive aging and improve clinical fertility assessment in mid-aged women.

• Research Paper Volume 12, Issue 6 pp 4945-4952

  Fasting blood glucose and cerebrospinal fluid Alzheimer’s biomarkers in non-diabetic cognitively normal elders: the CABLE study

  Relevance score: 5.432908

  Ya-Nan Ou, Xue-Ning Shen, He-Ying Hu, Hao Hu, Zuo-Teng Wang, Wei Xu, Qiang Dong, Lan Tan, Jin-Tai Yu

  Keywords: fasting blood glucose, Alzheimer's disease, β-amyloid, cerebrospinal fluid, gender

  Published in Aging on March 17, 2020

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  It is unclear how blood glucose levels mediate the pathology of Alzheimer's disease (AD). This study aimed to investigate whether fasting blood glucose (FBG) levels are associated with cerebrospinal fluid (CSF) biomarkers preferentially affected by AD in non-diabetic cognitively normal elders. A total of 499 non-diabetic cognitively normal elders were from the Chinese Alzheimer’s Biomarker and LifestyLE (CABLE) study. We detected the associations of FBG with individual CSF measures using multiple linear regression models controlling for age, sex, educational level, and apolipoprotein E (APOE) ε4 genotype. Fasting blood glucose level was positively correlated with CSF Aβ₄₂ level (β = 0.045, p = 0.010), CSF Aβ₄₂/Aβ₄₀ ratio (β = 0.005, p < 0.001), Aβ₄₂/P-tau ratio (β = 0.282, p = 0.013), and Aβ₄₂/T-tau ratio (β = 0.050, p = 0.040). Interaction analysis indicated that gender affected the correlations of FBG level with CSF Aβ₄₀ (p < 0.001) and Aβ₄₂/Aβ₄₀ ratio (p < 0.001). This study raises additional questions about the role of blood glucose in the predisposition to AD and supports the possibility of targeting these processes in pre-symptomatic AD trials in non-diabetic elders.

  

  Associations of elevated FBG with CSF Aβ₄₂, Aβ₄₂/P-tau ratio, and Aβ₄₂/T-tau ratio, and Aβ₄₂/Aβ₄₀ ratio in non-diabetic cognitively normal elders. The scatter plots depict the relations between FBG and (A) CSF Aβ₄₂, (B) Aβ₄₂/P-tau ratio, and (C) Aβ₄₂/T-tau ratio, and (D) Aβ₄₂/Aβ₄₀ ratio. All models were adjusted for age, sex, educational level, and APOE ε4 status. Abbreviations: FBG, fasting blood glucose; CSF, cerebrospinal fluid; Aβ, β-amyloid; T-tau, total-tau; phosphorylated-tau, P-tau; APOE ε4, apolipoprotein E ε4.

  
  
  

• Research Paper Volume 12, Issue 1 pp 978-995

  Metabolomic profiling of dried blood spots reveals gender-specific discriminant models for the diagnosis of small cell lung cancer

  Relevance score: 5.6791124

  Li Yu, Kefeng Li, Xiangmin Li, Chao Guan, Tingting Sun, Xiaoye Zhang

  Keywords: small cell lung cancer, dried blood spot, metabolomics, differential diagnosis, gender differences

  Published in Aging on January 12, 2020

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  The accurate diagnosis of small cell lung cancer (SCLC) at initial presentation is essential to ensure appropriate treatment. No validated blood biomarkers that could distinguish SCLC from non-small cell lung cancer (NSCLC) has yet been developed. Dried blood spot (DBS) microsampling has gained increasing interest in biomarkers discovery. In this study, we first performed metabolomic profiling of DBS samples from 37 SCLC, 40 NSCLC, and 37 controls. Two gender-specific multianalyte discriminant models were established for males and females, respectively to distinguish SCLC from NSCLC and controls. The receiver operator characteristic (ROC) curve analysis showed the diagnostic accuracy of 95% (95% CI: 83%-100%) in males SCLC using five metabolites in DBS and 94% (95% CI: 74%-100%) for females using another set of five metabolites. The robustness of the models was confirmed by the random permutation tests (P < 0.01 for both). The performance of the discriminant models was further evaluated using a validation cohort with 78 subjects. The developed discriminant models yielded an accuracy of 91% and 81% for males and females, respectively, in the validation cohort. Our results highlighted the potential clinical utility of the metabolomic profiling of DBS as a convenient and effective approach for the diagnosis of SCLC.

  

  The experimental flow for the study. Abbreviations: DBS = dried blood spot; LC-MS/MS = liquid chromatography coupled with tandem mass spectrometry; NSCLC = non-small cell lung cancer; SCLC = small cell lung cancer.

  
  
  

  

  The unique metabolic features of male SCLC compared to NSCLC and controls. (A, B) Multivariate analysis of metabolomic data using PLS-DA resulted in a clear separation of metabolic features among SCLC, NSCLC and the control group in males. (A) 2-D plot. (B) 3-D plot. (C) The top 15 most differential metabolites in male patients with SCLC revealed by VIP analysis. VIP>1.5 was considered as statistically significant. The VIP results were also verified by univariate ANOVA analysis. (D) The top pathways disturbed in male SCLC patients. Abbreviations: IMP = inosine monophosphate; Cer = Ceramide; SM = Sphingomyelin; PI = Phosphatidylinositol; NSCLC = non-small cell lung cancer; PLS-DA = partial least square discriminant analysis; SCLC = small cell lung cancer; VIP = variance in projection.

  
  
  

  

  The unique metabolic features in the DBS of female SCLC patients compared to NSCLC and noncancer controls. (A, B) Multivariate analysis of metabolomic data using PLS-DA resulted in a clear separation of metabolic features among SCLC, NSCLC and the control group in females. (A) 2-D plot. (B) 3-D plot. (C) The top 15 most differential metabolites in female patients with SCLC revealed by VIP analysis. VIP>1.5 was considered as statistically significant. The VIP results were also verified by univariate ANOVA analysis. (D) The top pathways disturbed in female SCLC patients. Abbreviations: DBS = dried blood spot; NSCLC = non-small cell lung cancer; PE = phosphatidylethanolamine; 9-HETE = 9-hydroxyeicosatetraenoic acid; 13-HODE = 13-Hydroxyoctadecadienoic acid; SM = Sphingomyelin; PLS-DA = partial least square discriminant analysis; SCLC = small cell lung cancer; VIP = variance in projection.

  
  
  

  

  The shared and unique metabolic signature between male and female patients with SCLC. (A) The common and unique disturbed pathways in male and female SCLC compared to NSCLC and controls. (B) Total 2-hydroxy (2-OH) ceramides were significantly higher in male SCLC, while, no differences were observed in female patients with SCLC. (C) Total unsaturated PE was dramatically lower in female SCLC without significant changes in male SCLC. One-way ANOVA followed by Tukey’s test. * P < 0.05 and ns: nonsignificant. Abbreviations: NSCLC = non-small cell lung cancer; PE = phosphatidylethanolamine; SCLC = small cell lung cancer.

  
  
  

  

  The diagnostic performance of the developed multianalyte discriminant model for male SCLC in the discovery set. (A–E) Violin plots showed the relative levels of five selected metabolites in the model. (A) PI(18:0/18:0); (B) Cer(d18:1/22:0 OH); (C) 2-Arachidonoylglycerol; (D) IMP; and (E) Cholic acid. The AUC ratio for each metabolite was calculated by the AUC of the corresponding internal standard. One-way ANOVA followed by Tukey’s test was used. *P < 0.05 and ns: nonsignificant. (F) ROC curve analysis for distinguishing male SCLC patients from NSCLC and controls. (G) The random permutation test to examine the robustness of the model. Permutation P-value represented the probability that the classification of SCLC and NSCLC and controls using the selected metabolites could be obtained by chance. (H) Multiple linear regression analysis showed a significant correlation between the five selected metabolites and serum neuron-specific enolase (NSE) in male SCLC patients. R² = 0.63, P < 0.01. Abbreviations: IMP = inosine monophosphate; PI = Phosphatidylinositol; Cer = Ceramide; NSCLC = non-small cell lung cancer; NSE = neuron-specific enolase; ROC = receiver operator characteristic; SCLC = small cell lung cancer.

  
  
  

  

  The diagnostic performance of the developed multianalyte discriminant model for female SCLC in the discovery set. (A–E) Violin plots showed the relative levels of five selected metabolites in the female discriminant model. (A) PE (18:1/20:4); (B) 5-Methyltetrahydrofolic acid; (C) Desmosterol; (D) 4, 5-Dihydroorotic acid and (E) 9-HETE. (F) ROC curve analysis for distinguishing female SCLC patients from female NSCLC and controls. (G) The random permutation test to examine the robustness of the female discriminant model. (H) Multiple linear regression analysis showed a significant correlation between the five selected metabolites and NSE in female SCLC patients. R² = 0.56, P < 0.05. Abbreviations: NSCLC = non-small cell lung cancer; PE = phosphatidylethanolamine; 9-HETE = 9-hydroxyeicosatetraenoic acid; ROC = receiver operator characteristic; SCLC = small cell lung cancer.

  
  
  

• Research Paper Volume 12, Issue 1 pp 288-308

  Associations of lifestyle activities and a heathy diet with frailty in old age: a community-based study in Singapore

  Relevance score: 5.682724

  Xiu Wang, Yanxia Lu, Chunbo Li, Anis Larbi, Liang Feng, Qingfeng Shen, Mei Sian Chong, Wee Shiong Lim, Lei Feng

  Keywords: frailty, lifestyle activity, healthy diet, risk factors, gender differences

  Published in Aging on January 2, 2020

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  Frailty is an age-related state characterized by a reduced physiological reserve, and is associated with adverse health outcomes in the elderly. We analyzed the data from 895 adults aged 60 years and above, and investigated the relationships between midlife and late-life social activities, intellectual activities, working hours, and dietary habits and frailty status. Participation in social or intellectual activities in late life was less prevalent among those who were frail than among those who were robust. A greater proportion of those who were frail had worked long hours in midlife. After adjustment for confounders, participating in social activities or intellectual activities in late life was associated with a reduced risk for prefrailty and frailty, while working long hours in midlife was associated with a higher risk for frailty. The risk of frailty decreased with increasing healthy diet scores in midlife and late life. When the results were stratified by gender, late-life participation in social activities and midlife or late-life participation in intellectual activities correlated negatively with prefrailty/frailty only in women. Our study suggests that social and intellectual activities are inversely associated with frailty status, but the association seems to differ based on gender.

• Editorial Volume 11, Issue 24 pp 11795-11796

  The impact of age on long QT syndrome

  Relevance score: 5.9258256

  Norbert Guettler, Kim Rajappan, Edward Nicol

  Keywords: inherited long QT syndrome (LQTS), childhood, adolescence, aging, gender

  Published in Aging on December 28, 2019

• Research Paper Volume 11, Issue 19 pp 8573-8586

  High body mass index, brain metabolism and connectivity: an unfavorable effect in elderly females

  Relevance score: 6.244263

  Arianna Sala, Maura Malpetti, Anna Ferrulli, Luigi Gianolli, Livio Luzi, Daniela Perani,

  Keywords: body mass index, connectivity, PET, brain, gender

  Published in Aging on October 9, 2019

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  There are reported gender differences in brain connectivity associated with obesity. In the elderlies, the neural endophenotypes of obesity are yet to be elucidated. We aim at exploring the brain metabolic and connectivity correlates to different BMI levels in elderly individuals, taking into account gender as variable of interest.

  We evaluated the association between BMI, brain metabolism and connectivity, in elderly females and males, by retrospectively collecting a large cohort of healthy elderly subjects (N=222; age=74.03±5.88 [61.2-85.9] years; M/F=115/107; BMI=27.00±4.02 [19.21-38.79] kg/m²). Subjects underwent positron emission tomography with [18F]FDG. We found that, in females, high BMI was associated with increased brain metabolism in the orbitofrontal cortex (R=0.44; p<0.001). A significant BMI-by-gender interaction was present (F=7.024, p=0.009). We also revealed an altered connectivity seeding from these orbitofrontal regions, namely expressing as a decreased connectivity in crucial control/decision making circuits, and as an abnormally elevated connectivity in reward circuits, only in females. Our findings support a link between high BMI and altered brain metabolism and neural connectivity, only in elderly females. These findings indicate a strong gender effect of high BMI and obesity that brings to considerations for medical practice and health policy.

  

  Gender-specific voxel-wise correlation between BMI levels and brain metabolism. (A) A significant positive correlation was found in orbitofrontal regions (partial R=0.44) in females. Statistical threshold was set at p<0.001 (uncorrected for multiple comparisons), with minimum cluster extent Ke:100 voxels (yellow). For visualization purposes, figure also shows voxels where correlation is significant at a more liberal threshold (p<0.01 uncorrected for multiple comparison; red). For both p<0.001 and p<0.01 voxel-level thresholds, only clusters surviving p<0.05 FWE-correction are shown. BrainNet Viewer (http://www.nitrc.org/projects/bnv/) was used for rendering [53]. (B) Scatter plot shows the significant BMI by gender interaction on orbitofrontal metabolism, with females showing a significant positive correlation between BMI levels (x axis) and average SPM-T values of glucose metabolism (y axis) (R=0.31, p<0.001; partial R=0.44, p<0.001) and males showing no correlation at all (R=-0.07, p=0.492; partial R=-0.01, p=0.881). Positive SPM-T values indicate higher-than-average mean orbitofrontal glucose metabolism: in females, higher BMI levels are associated with increased orbitofrontal glucose metabolism, crucially approaching critical hypermetabolism levels in the case with highest BMI levels (BMI ≈ 40kg/m2). Shaded areas represent confidence intervals for the regression line slope in each group. (C) Scatter plot shows the lack of a significant BMI by age interaction on orbitofrontal metabolism, despite of a significant principal effect of age (partial R=0.32, p<0.001), in the female cohort. The slope of the regression lines in the different (normal, overweight and obese) BMI groups does not differ: there is no significant interaction effect between age and BMI, but both age and BMI have an independent effect on orbitofrontal metabolism. Age (years) is plotted on the x axis and metabolism on the y axis. Shaded areas represent confidence intervals for the regression line slope in each group.

  
  
  

  

  Gender-specific ROI-based correlations between BMI levels and regional metabolism. Graph shows significant correlations between BMI levels (x axis) and average SPM-T values of glucose metabolism in a series of a priori selected ROIs (y axis), in the female cohort. Positive SPM-T values indicate higher-than-average brain glucose metabolism in each ROI, as obtained through comparison with a reference control sample [see text]. Higher BMI levels are associated with increased glucose metabolism. Only ROIs where correlation is significant after Bonferroni correction are shown. Gray shaded areas represent confidence intervals for the regression line slope.

  
  
  

  

  Results of the data-driven metabolic connectivity analysis in females. Figure shows results of the data-driven metabolic connectivity analysis, seeding from the BMI-related orbitofrontal cluster identified through whole-brain correlation analysis (see Figure 1 and text). The pattern of connectivity of the orbitofrontal cluster in females with normal BMI (upper panel) remarkably differs from the one observed in females with high BMI (lower panel) (A). In females with high BMI, loss of connectivity is evident between orbitofrontal cortex and high-order cortical regions, notably the dorsolateral prefrontal cortex (red arrows). Interconnections with reward-related brain circuits are also present (lacking in females with normal BMI), specifically involving the medial orbitofrontal cortex and nucleus accumbens (red arrows). Threshold for statistical significance was set at p<0.001 (uncorrected for multiple comparisons), minimum cluster extent k:100 voxels. Only clusters surviving SPM cluster-level FWE-correction (p<0.05) are shown Significant differences in connectivity strength between females with high BMI and females with normal BMI are also shown (p<0.01, uncorrected for multiple comparisons; p<0.05 at cluster-level; Ke: 100 voxels) (B). A high-resolution MRI anatomical template in MRIcron was used for rendering.

  
  
  

• Research Paper Volume 11, Issue 2 pp 707-723

  Age-related immune-modulating properties of seminal fluid that control the severity of asthma are gender specific

  Relevance score: 8.04797

  Yuichi Niikura, Takashi Ishii, Jurika Murakami, Tomoya Narita, Yoko Fujita, Hiroaki Negishi, Yuji Taketani, Naomi Yamashita

  Keywords: aging, asthma, gender difference, seminal fluid

  Published in Aging on January 24, 2019

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  Reproductive organs play a pivotal role in asthma development and progression, especially in women. Endocrine environment changes associated with the menstrual cycle, pregnancy, and menopause can exacerbate the clinical features of asthma. Factors secreted by reproductive organs may be responsible for the gender difference and age-related changes in adult asthma. Here, we show that mammalian seminal fluid has anti-asthma effects exclusively in females. Exposure to murine seminal fluid markedly reduced eosinophilic airway inflammation in 2-month-old female mice upon ovalbumin inhalation. The anti-asthma effect with seminal fluid from 10-month-old males was double that with fluid from 2-month-old males, suggesting that it depended on male sexual maturation. We further found that seminal fluid from middle-aged human volunteers had beneficial effects in asthmatic female mice; these effects were associated with transcriptional repression of osteopontin and IL-17A, which are poor prognostic factors for asthma. In 2-month-old male mice, however, human seminal fluid failed to decrease asthmatic features and even enhanced osteopontin and IL-17A transcription. Our data demonstrate that age-related seminal fluid exerts opposing effects in asthmatic male and female mice. These findings may help the development of novel approaches to control the prevalence and age-related progression of asthma in women.

  

  Murine seminal fluid ameliorates asthmatic features in adult female mice. (A) Schematic representation of experimental design for murine seminal fluid (SF) exposure. Young adult female mice sensitized with ovalbumin (OVA) were given murine SF intraperitoneally 30 min before OVA challenge. (B) Age-related functional alteration in murine SF in asthmatic female mice. Numbers of eosinophils (Eos) in bronchoalveolar lavage fluid (BALF) of asthmatic female mice exposed to epididymal fluid (EpF) from 2-month-old (2M) or 10-month-old (10M) male mice are shown. White box: control group (n = 3); colored boxes: asthma groups (n = 6–12). Data are presented as means ± SEM. **P < 0.01 and *P < 0.05 versus OVA asthma group. (C) Changes in Th2-cell-driven allergic responses in asthmatic female mice exposed to 10M-seminal vesicle fluid (SVF) or 10M-EpF. Eosinophil number, IL-13 section, and OVA-specific IgE antibody production are shown. White box: control group (n = 3); colored boxes: asthma groups (n = 5 each). Data are presented as means ± SEM. **P < 0.01 and *P < 0.05 versus OVA asthma group. (D) Representative images of airway inflammation and mucus-producing cell hyperplasia in lungs from asthmatic female mice exposed to 10M-SVF or 10M-EpF. Hematoxylin and eosin (HE, upper) and periodic acid-Schiff (PAS, lower) staining reveals immune cell infiltration and mucus-producing cell hyperplasia, respectively. AW: airway.

  
  
  

  

  Human seminal fluid improves pathological changes in asthmatic female mice. (A) Changes in Th2-cell-driven allergic responses in asthmatic female mice exposed to human seminal fluid (hSF). White box: control group (n = 3); colored boxes: asthma groups (n = 7 each). Data are presented as means ± SEM. **P < 0.01 and *P < 0.05 versus ovalbumin (OVA) asthma group. (B) Representative images of PAS staining of lungs from asthmatic female mice exposed to hSF. AW: airway. (C) Assessment of airway hyper-responsiveness in asthmatic female mice exposed to hSF. The response to methacholine at each dose was quantified as the average of the peak measurements of airway resistance (Rrs). control group (n = 3, black); OVA asthma groups (n = 5, red); hSF/OVA group (n = 5, blue). Data are presented as means ± SEM. **P < 0.01 and *P < 0.05 versus OVA asthma group. (D) Transcriptional repression of osteopontin and IL-17A in lungs from asthmatic female mice exposed to hSF. White box: control group (n = 3); colored boxes: asthma groups (n = 7 each). Data are presented as means ± SEM. *P < 0.05 versus OVA asthma group. (E) Transcriptional repression of osteopontin by hSF in antigen-stimulated bone-marrow-derived dendritic cells (BM-DCs) of 2-month-old female mice. White box: control group (n = 8); colored boxes: OVA-stimulated groups (n = 8 each). Data are presented as means ± SEM. *P < 0.05 versus OVA group. BM: bone marrow, GM-CSF: granulocyte macrophage colony-stimulating factor.

  
  
  

  

  Human seminal fluid does not improve pathological changes in asthmatic male mice. (A) Schematic representation of experimental design for human seminal fluid (hSF) exposure. Young adult male mice sensitized with ovalbumin (OVA) were given hSF intraperitoneally 30 min before OVA challenge. (B) Changes in Th2-cell-driven allergic responses in asthmatic male mice exposed to hSF. White box: control group (n = 3); colored boxes: asthma groups (n = 5–7). Data are presented as means ± SEM. *P < 0.05 versus OVA asthma group. (C) Representative images of PAS staining of lungs of asthmatic male mice exposed to hSF. AW: airway. (D) Transcriptional induction of osteopontin and IL-17A in lungs of asthmatic male mice exposed to hSF. White box: control group (n = 3); colored boxes: asthma groups (n = 5 - 7). Data are presented as means ± SEM. *P < 0.05 versus OVA asthma group. (E) Transcriptional induction of osteopontin by hSF in antigen-stimulated BM-DCs of 2-month-old male mice. White box: control group (n = 3); colored boxes: OVA-stimulated groups (n = 6 each). Data are presented as means ± SEM. *P < 0.05 versus OVA group.

  
  
  

  

  Enhanced transcription of osteopontin and IL-17A in lungs of asthmatic mature male mice. (A) Schematic representation of experimental design for asthma induction in mature male mice. Sensitized young adult male mice were challenged with ovalbumin (OVA) at 10 months of age. (B) Changes in Th2-cell-driven allergic responses in asthmatic mature male mice. White box: control group (n = 3); colored boxes: asthma groups (n = 5 - 7). (C) Representative images of PAS staining of lungs from asthmatic mature male mice. AW: airway. (D) Enhanced transcription of osteopontin and IL-17A in lungs of asthmatic mature male mice. White box: control group (n = 3); colored boxes: asthma groups (n = 5–7). Data are presented as means ± SEM. **P < 0.01 and *P < 0.05 versus young OVA asthma group.

  
  
  

  

  Age-related functional alteration of seminal fluid in pathogenesis of adult asthma. Factor A in young adult males exerts anti-inflammatory activity and may contribute to a low basal immune response compared with that in young adult females (Figure 1C and Figure 3B–D). In contrast, Factor B presents in sexually mature males and seems to exert pro-inflammatory activity (Figure 3D and Figure 4D). Both Factors A and B exhibit anti-inflammatory functions in young adult asthmatic female mice (Figure 1C). The presence of these two factors is likely associated with the gender bias and age-related progression of adult asthma.

  
  
  

• Research Paper Volume 10, Issue 8 pp 2148-2169

  Gender- and region-specific changes in estrogen signaling in aging rat brain mitochondria

  Relevance score: 6.572314

  Christopher M. Evola, Tanner L. Hudson, Luping Huang, Adrian M. Corbett, Debra A. Mayes

  Keywords: aging, gender, ER-beta, neurodegeneration, mitochondria

  Published in Aging on August 31, 2018

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  Recently epidemiological studies suggest females lose neuroprotection from neurodegenerative diseases as they go through menopause. It has been hypothesized that this neuroprotection is hormone-dependent. The current study characterized cell signaling molecules downstream of estrogen receptor beta that are known to play a role in memory, PKC, ERK, and connexin-43, in regions of the brain associated with memory decline in an attempt to elucidate significant changes that occur post-estrus. Total whole cell lysates were compared to isolated mitochondrial protein because mitochondrial function is known to be altered during aging. As hypothesized, protein concentrations differed depending on age, gender, and brain region. Additionally, many of these changes occurred within mitochondria but not within whole cell lysates indicating that these are epigenetic alterations. These findings accentuate the complexity of aging and provide insight into the gender-specific cellular processes that occur throughout this process.

  

  Signaling downstream of estrogen in the cerebral cortex across age and gender. Representative western blots for each protein of interest and a representative Ponceau stain as a load control (A). Graphical depiction of the fold change for p-ERK (B), p-PKC (C), ERK (D), ERK (E), p-cx43 (F), cx43 (G), beta-actin (H). Error bars = SEM. 4W = 4 weeks of age; 3M = 3 months of age; 9M = 9 months of age; 12M = 12 months of age. Pink = female; blue = male. ANOVA with Tukey posthoc, * = P<0.05.

  
  
  

  

  Signaling downstream of estrogen in the mitochondria of the cerebral cortex across age and gender. Representative western blots for each protein of interest and a representative Ponceau stain as a load control (A). Graphical depiction of the fold change for p-cx43 comparing age (B), p-cx43 comparing gender (C), cx43 (D), estrogen receptor beta (E), PKC (F), ATP synthase (G). Error bars = SEM. 4W = 4 weeks of age; 3M = 3 months of age; 9M = 9 months of age; 12M = 12 months of age. Pink = female; blue = male. ANOVA with Tukey posthoc, * = P<0.05.

  
  
  

  

  Signaling downstream of estrogen in the hippocampus across age and gender. Representative western blots for each protein of interest and a representative Ponceau stain as a load control (A). Graphical depiction of the fold change for p-PKC (B), PKC comparing age (C), PKC comparing gender (D), cx43 comparing age (E), cx43 comparing gender (F), p-cx43 (G), p-ERK (H), ERK (I), beta-actin (J). Error bars = SEM. 4W = 4 weeks of age; 3M = 3 months of age; 9M = 9 months of age; 12M = 12 months of age. Pink = female; blue = male. ANOVA with Tukey posthoc, * = P<0.05. Pink * = p<0.05 for females only.

  
  
  

  

  Signaling downstream of estrogen in the mitochondria of the hippocampus across age and gender.Representative western blots for each protein of interest and a representative Ponceau stain as a load control (A). Graphical depiction of the fold change for p-cx43 comparing age (B), p-cx43 comparing gender (C), cx43 comparing age (D), cx43 comparing gender (E), estrogen receptor beta (F), PKC (G), ATP synthase (H). Error bars = SEM. 4W = 4 weeks of age; 3M = 3 months of age; 9M = 9 months of age; 12M = 12 months of age. Pink = female; blue = male. ANOVA with Tukey posthoc, * = P<0.05. Pink * = p<0.05 for females only.

  
  
  

  

  Signaling downstream of estrogen in the amygdala across age and gender. Representative western blots for each protein of interest and a representative Ponceau stain as a load control (A). Graphical depiction of the fold change for p-PKC (B), PKC (C), p-ERK (D), ERK (E), p-cx43 (F), cx43 (G), beta-actin (H). Error bars = SEM. 4W = 4 weeks of age; 3M = 3 months of age; 9M = 9 months of age; 12M = 12 months of age. Pink = female; blue = male. ANOVA with Tukey posthoc, * = P<0.05.

  
  
  

  

  Signaling downstream of estrogen in the mitochondria of the amygdala across age and gender. Representative western blots for each protein of interest and a representative Ponceau stain as a load control (A). Graphical depiction of the fold change for PKC comparing age (B), PKC comparing gender (C), p-cx43 (D), cx43 (E), estrogen receptor beta (F), ATP synthase (G). Error bars = SEM. 4W = 4 weeks of age; 3M = 3 months of age; 9M = 9 months of age; 12M = 12 months of age. Pink = female; blue = male. ANOVA with Tukey posthoc, * = P<0.05.

  
  
  

  

  Signaling downstream of estrogen in the corpus callosum across age and gender. Representative western blots for each protein of interest and a representative Ponceau stain as a load control (A). Graphical depiction of the fold change for p-PKC (B), p-ERK (C), p-cx43 comparing gender (D), PKC (E), ERK (F), cx43 (G), beta-actin (H). Error bars = SEM. 4W = 4 weeks of age; 3M = 3 months of age; 9M = 9 months of age; 12M = 12 months of age. Pink = female; blue = male. ANOVA with Tukey posthoc, * = P<0.05.

  
  
  

  

  Signaling downstream of estrogen in the mitochondria of the corpus callosum across age and gender. Representative western blots for each protein of interest and a representative Ponceau stain as a load control (A). Graphical depiction of the fold change for PKC (B), p-cx43 (C), estrogen receptor beta (D), cx43 (E), ATP synthase (F). Error bars = SEM. 4W = 4 weeks of age; 3M = 3 months of age; 9M = 9 months of age; 12M = 12 months of age. Pink = female; blue = male. ANOVA with Tukey posthoc, * = P<0.05.

  
  
  

  

  Signaling downstream of estrogen in the cerebellum across age and gender. Representative western blots for each protein of interest and a representative Ponceau stain as a load control (A). Graphical depiction of the fold change for for cx43 with age (B), p-PKC (C), PKC (D), ERK (E),ERK (F), p-cx43 (G), beta-actin (H). Error bars = SEM. 4W = 4 weeks of age; 3M = 3 months of age; 9M = 9 months of age; 12M = 12 months of age. Pink = female; blue = male. ANOVA with Tukey posthoc, * = P<0.05.

  
  
  

  

  Signaling downstream of estrogen in the mitochondria of the cerebellum across age and gender. Representative western blots for each protein of interest and a representative Ponceau stain as a load control (A). Graphical depiction of the fold change for estrogen receptor beta (B), PKC (C), p-cx43 (D), cx43 (E), ATP synthase (F). Error bars = SEM. 4W = 4 weeks of age; 3M = 3 months of age; 9M = 9 months of age; 12M = 12 months of age. Pink = female; blue = male. ANOVA with Tukey posthoc, * = P<0.05.

  
  
  

  

  Schematic representation of a potential mechanism by which loss of estrogen post estrus can result in decreased mitochondrial function and increased permeability of the Blood Brain Barrier.

  
  
  

• Research Paper Volume 8, Issue 11 pp 2848-2861

  No effect of testosterone on behavior in aged Wistar rats

  Relevance score: 6.8590174

  Veronika Borbélyová, Emese Domonkos, Janka Bábíčková, Ľubomíra Tóthová, Martin Bosý, Július Hodosy, Peter Celec

  Keywords: andropause, gender, aging, steroids, brain functions

  Published in Aging on November 12, 2016

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  In men, aging is accompanied by a gradual decline in androgen secretion. Studies suggest beneficial effects of endogenous and exogenous testosterone on affective behavior and cognitive functions. The aim of this study was to describe behavioral and cognitive sex differences and to analyze the effects of long-term androgen deficiency in aged male rats. Thirty-months old rats divided into three groups (males, females and males gonadectomized as young adults) underwent a battery of behavioral tests assessing locomotor activity, anxiety, memory, anhedonia, sociability and depression-like behavior. No major effect of gonadectomy was found in any of the analyzed behavioral measures in male rats. The only consistent sex difference was confirmed in depression-like behavior with longer immobility time observed in males. In an interventional experiment, a single dose of testosterone had no effect on gonadectomized male and female rats in the forced swim test. In contrast to previous studies this comprehensive behavioral phenotyping of aged rats revealed no major role of endogenous testosterone. Based on our results long-term hypogonadism does not alter the behavior of aged male rats, neither does acute testosterone treatment. Whether these findings have any consequences on androgen replacement therapy in aged men remains to be elucidated.

  

  Locomotor activity of aged rats in the open field test. (A, B) Horizontal and (C) vertical locomotor activity for males (white bar), GDX males (black bar) and females (grey bar). There were no significant differences between groups in horizontal locomotor activity. Females had a significantly higher vertical locomotor activity compared to both male groups (p<0.05). Data are expressed as means + SEM. *p<0.05.

  
  
  

  

  Anxiety-like behavior in aged rats. (A) Time spent in the center zone of the open field, (B) time spent in the light zone of the light/dark box and (C) time spent in the open arms of the elevated plus maze. No significant difference between the groups was found in the time spent in the center zone. GDX males were less anxious than males in light/dark box (p<0.01). There was no significant difference in the time spent in open arms between groups in elevated plus maze. Males (white bar), GDX males (black bar) and females (grey bar). Values are expressed as means + SEM. **p<0.01.

  
  
  

  

  Exploratory activity and memory in aged rats. (A) Total time spent interacting with each individual object in trial 1 and (B) in trial 2. (C) Absolute time difference between investigating the sample and novel object. There were no significant differences in any of observed parameters between groups. Males (white bar), GDX males (black bar) and females (grey bar). Values are expressed as means + SEM.

  
  
  

  

  Sociability and preference for social novelty in aged rats. (A) Total social interaction time in trial 1 and (B) trial 2. (C) Preference for novel social partner in trial 2 for males (white bar), GDX males (black bar) and females (grey bar). There were no statistically significant differences in the analyzed parameters between groups. Data are expressed as means + SEM.

  
  
  

  

  Immobility duration in the forced swim test. Immobility time in the (A) 1^st min, (B) 2^nd min, (C) 3^rd min, (D) during the total of 3 min testing period, (E) the latency to first immobility and (F) duration of the immobility taken minute by minute over the 3 min testing period. Males had longer immobility duration in the 1^st min and 3^rd min compared to females (p<0.05). This difference was also observed in total immobility time during the 3 min testing period (p<0.05). GDX males displayed a shorter latency to first immobility compared to females (p<0.05). Males (white bar), GDX males (black bar) and females (grey bar). Data are expressed as means + SEM. *p<0.05, ***p<0.001.

  
  
  

  

  Sucrose preference test. Percentual preference for 2% sucrose solution of total 24h liquid intake. No differences in the preference for sucrose between the groups was detected. Males (white bar), GDX males (black bar) and females (grey bar). Values are expressed as means + SEM.

  
  
  

  

  Locomotor activity and anxiety-like behavior of aged rats in instrumented observation cage. (A, B) No significant differences between the groups were found in locomotor activity. (C) GDX males spent significantly less time in the center zone than males. Males (white bar), GDX males (black bar) and females (grey bar). Values are expressed as means + SEM. *p<0.05.

  
  
  

  

  Plasma testosterone concentration. (A) Plasma testosterone concentration 4 weeks following gonadectomy. Gonadectomy led to a significantly lower testosterone concentration compared to control males (p<0.01). Males (white bar) and GDX males (black bar). (B) Plasma testosterone concentration in young and aged male rats. Aged males (30 months) had significantly lower plasma testosterone concentration compared to young males (p<0.001) [young males (white bar), aged males (black bar)]. Values are expressed as means + SEM. **p<0.01, ***p<0.001.

  
  
  

  

  Immobility duration in forced swim test after acute testosterone treatment. (A) Plasma testosterone concentration 30 minutes after acute treatment with olive oil vehicle (VEH) or testosterone propionate (TP) in aged GDX males and aged females. Acute testosterone treatment caused an increase in plasma testosterone concentration in both GDX males and females compared to their vehicle treated controls (p<0.01). (B) Immobility time in the forced swim test during the 3 min testing period, (C) immobility duration in the 1^st min, (D) 2^nd min, (E) 3^rd min and (F) the latency to first immobility without any significant differences in observed behavioral parameters between groups. Values are expressed as means + SEM. *p<0.05, **p<0.01. Females+VEH (grey bar), Females+TP (grey striped bar), GDX+VEH males (black bar), GDX+TP males (black striped bar).

  
  
  

• Research Paper Volume 7, Issue 6 pp 412-418

  The influence of gender on inheritance of exceptional longevity

  Relevance score: 7.6635847

  Jennifer A. Deluty, Gil Atzmon, Jill Crandall, Nir Barzilai, Sofiya Milman

  Keywords: centenarians, longevity, gender, inheritance

  Published in Aging on June 22, 2015

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  While the search for genetic contributors to exceptional longevity has yielded candidates, gender differences in inheritance have generally not been considered. The aim of this study was to investigate gender specific differences in the inheritance of exceptional longevity. Using a standardized questionnaire, we assessed the parental ages of death of Ashkenazi Jews with exceptional longevity and their spouses without exceptional longevity, who served as controls (n=1,114). Mothers of centenarian males and females had significantly longer lifespans compared to the mothers of non‐ centenarians, 79.0 ± 13.4 vs. 73.0 ± 16.3 years, p<0.01 and 75.7 ± 15.8 vs. 70.5 ± 18.0 years, p=0.02, respectively. There was also a trend toward longer lifespan among the fathers of centenarian men compared to the lifespan of fathers of non‐ centenarian men, 73.5 ± 17.0 vs. 69.5 ±15.0 years, p=0.07. The lifespan did not differ between the fathers of centenarian and non‐centenarian daughters. Logistic regression models revealed that the odds of being a centenarian for the female and male offspring increased by 21% and 31%, respectively, for every additional 10 years of life achieved by the mother (p<0.05). These findings support a gender‐specific inheritance pattern of human longevity and may help focus the search for longevity genes.

  

  Offspring provided information about their parents and grandparents. If the parent was > 95 years of age (centenarian), the grandparents of that lineage were deemed as cases. If the parent was <95 years of age (non‐centenarian), the grandparents of that lineage were deemed as controls.

  
  
  

  

  Comparison between the average parental ages at death among centenarians and non‐centenarians for both genders of centenarians combined, females only and males only.

  
  
  

  

  Maternal and paternal ages at death among the parents of centenarians and non‐centenarians. A. Both genders of centenarians combined. B. Females only. C. Males only.

  
  
  

• Review Volume 6, Issue 2 pp 84-91

  Evolution of sexually dimorphic longevity in humans

  Relevance score: 6.753426

  David Gems

  Keywords: aging, eunuch, evolution, gender gap, menopause, polygyny, testosterone

  Published in Aging on February 22, 2014

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  Why do humans live longer than other higher primates? Why do women live longer than men? What is the significance of the menopause? Answers to these questions may be sought by reference to the mechanisms by which human aging might have evolved. Here, an evolutionary hypothesis is presented that could answer all three questions, based on the following suppositions. First, that the evolution of increased human longevity was driven by increased late-life reproduction by men in polygynous primordial societies. Second, that the lack of a corresponding increase in female reproductive lifespan reflects evolutionary constraint on late-life oocyte production. Third, that antagonistic pleiotropy acting on androgen-generated secondary sexual characteristics in men increased reproductive success earlier in life, but shortened lifespan. That the gender gap in aging is attributable to androgens appears more likely given a recent report of exceptional longevity in eunuchs. Yet androgen depletion therapy, now used to treat prostatic hyperplasia, appears to accelerate other aspects of aging (e.g. cardiovascular disease). One possibility is that low levels of androgens throughout life reduces aging rate, but late-life androgen depletion does not

  

  This shows an example of fertility distributions in a polygynous population (Northern Ghana) [17, 20] (figure kindly prepared by D. van Bodegom).

  
  
  

  

  Hypothetical scheme showing the evolutionary origins of human longevity (relative to other higher primates), the gender gap in lifespan, and the menopause. Numbers and curves are intended to represent general trends rather than precise values.

  
  
  

• Research Paper pp undefined-undefined

  Gender-specification lifestyle factors associated with mild cognitive impairment among young-old adults in Taiwan

  Relevance score: 5.432908

  Su-Wen Chuang, Ching-Wen Chen, Meng-Chang Lee, Yu-Hsuan Chen, Wen Su, Cheng-Jung Chen, Wei-Teing Chen, Po-Jen Hsiao, Chih-Chien Chiu, Sui-Lung Su

  Keywords: young-old, mild cognitive impairment (MCI), MMSE, lifestyle, gender-specification

  Published in Aging on Invalid Date

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  Background: The prevalence of mild cognitive impairment (MCI) exhibits a positive correlation with age, particularly evident in the old-old female population. Lifestyle factors have been identified as crucial risk determinants for MCI. However, there is a scarcity of research focusing on lifestyle factors among young-old population.

  Objective: This study aimed to explore the lifestyle factors associated with MCI in young-old male and female.

  Methods: This study employed a cross-sectional design and utilized demographic and lifestyle data obtained from participants enrolled in the Taiwan Biobank (TWB) between 2008 and 2021, with 32,897 individuals aged 60 to 70 years old. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with a total score ranging from 0 to 30 points. The cut-off of MCI scores was ≤18, ≤21, and ≤25 according to the education level, respectively. Logistic regression analysis was employed to assess the association between lifestyles and cognitive function.

  Results: 3,878 individuals (11.78%) suffered from MCI. Upon gender stratification, high exercise metabolic equivalents in male (OR = 0.8, 95% CI: 0.70 - 0.92) and moderate exercise in female serve as protective factors for MCI (OR = 0.78, 95% CI: 0.70 - 0.87). Additionally, diversified dietary preferences among female (OR = 0.80, 95% CI: 0.66 - 0.97) also emerge as protective factors for cognitive function.

  Conclusions: It is worth noting that male is advised to target a higher exercise metabolic equivalent, while female can attain cognitive benefits with moderate exercise and diversified dietary.

• Research Paper pp undefined-undefined

  Gender difference in appendicular muscle strength: determinant of the quality of life in the older Taiwanese

  Relevance score: 3.9200819

  Mei-Jung Chen, Pi-Shao Ko, Meng-Chang Lee, Sui-Lung Su, Shu Yu

  Keywords: quality of life (QoL), muscle mass percentage, fat mass percentage, 12-Item Short Form Survey (SF-12), gender difference

  Published in Aging on Invalid Date

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  Background: The loss of skeletal muscle mass by aging determines the health status and the quality of life (QoL).

  Objective: To examine the relationships between appendicular muscle strength and the QoL of elderly adults in gender difference.

  Methods: This was a cross-sectional study, in which 690 subjects who participated in older adults health examination in the health management center of Tri-Service General Hospital from 2018 to 2021. A structured questionnaire was used to collect basic demographic data. The 12-Item Short Form Survey (SF-12) was used to evaluate the QoL of subjects. Their grip strength and gait speed were measured, and Dual-energy X-ray absorptiometry was used to measure muscle mass and other body composition data. Multivariate regression analysis was used to examine the relationships between upper and lower limb muscle strength and the QoL of older adults.

  Results: In men, legs muscle mass percentage (LegsMM%) (β = 3.67; 95% CI: 0.64–6.69; p = 0.018) and gait speed (β = 6.09; 95% CI: 3.88–8.30; p < 0.001) were positively associated with physical component summary (PCS) scores, and gait speed (β = 4.63; 95% CI: 2.66–6.60; p < 0.001) was also related to an improvement mental component summary (MCS) scores. In women, arms muscle mass percentage (ArmsMM%) (β = 6.50; 95% CI: 2.34–10.66; p = 0.002) and grip strength (β = 10.54; 95% CI: 6.27–14.81; p < 0.001) had the greatest effect on improving PCS scores, whereas grip strength (β = 7.58; 95% CI 4.00–11.17; p < 0.001) was also found to help improve MCS scores.

  Conclusions: Men should focus on lower limb training, whereas females should focus on upper limb training to effectively improve their QoL. Appropriate exercise interventions should be designed for different genders for the promotion of the healthy aging policy.