The Journals of Gerontology Series A: Biological Sciences and Medical Sciences最新文献

{"title":"Exploring the Shared Genetic Architecture of Sarcopenia Using Genomic Structural Equation Modeling","authors":"Yusheng Li, Peizhen Zhang, Qiaoling Chen, Jiacheng Zhang, Hongyi Wang, Wei Zhang, Huanan Li, Jingui Wang","doi":"10.1093/gerona/glag204","DOIUrl":"https://doi.org/10.1093/gerona/glag204","url":null,"abstract":"Background Sarcopenia is a common age-associated condition characterized by the progressive loss of skeletal muscle mass, strength, and physical functionality. While large-scale genome-wide association studies (GWAS) have previously addressed isolated traits of sarcopenia, the multifactorial genetic architecture underlying this condition remains largely undefined. Methods To characterize the common genetic basis of sarcopenia-related traits, genomic structural equation modeling (Genomic-SEM) was implemented. Multiple post-GWAS analytic approaches were integrated to pinpoint susceptibility loci. These analyses encompassed identifying enriched genetic pathways and relevant genomic elements, as well as cell-type-specific enrichment in skeletal muscle satellite stem cells, mesenchymal stem cells, and skeletal muscle satellite cells in limb muscle. Furthermore, based on the integrated GWAS data of sarcopenia-related traits, polygenic risk score (PRS) analysis was conducted to evaluate risk associations at the chromosomal level. Results A well-fitted Genomic-SEM successfully integrated the GWAS data, revealing the shared genetic architecture of sarcopenia-related traits. We identified 110 single nucleotide polymorphisms (SNPs) reaching genome-wide significance (P < 5 × 10−8), of which 9 represent novel discoveries. Subsequent fine-mapping procedures and gene-set analyses identified 15 causal variants alongside 77 candidate susceptibility genes. Conclusion This study provides a comprehensive genetic characterization of sarcopenia via Genomic-SEM, offering new insights into the etiological pathways underlying sarcopenia.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"347 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examining the relationship between D3Cr muscle mass, physical performance, and functional limitation in postmenopausal women","authors":"Hailey R Banack, Christopher Kim, Jean Wactawski Wende, Elizabeth C Feliciano, Bette J Caan, Garnet L Anderson, Heather M Ochs-Balcom, Catherine Lee, Mahalakshmi Shankaran, William J Evans","doi":"10.1093/gerona/glag200","DOIUrl":"https://doi.org/10.1093/gerona/glag200","url":null,"abstract":"Background The D3-creatine (D3Cr) dilution method provides a non-invasive and accurate assessment of muscle mass. Our objective was to examine the relationship between D3Cr muscle mass, objective measures of physical performance, and self-report physical function postmenopausal women. Methods We enrolled 2382 women from the Women’s Health Initiative (WHI) cohort to complete the D3Cr dilution protocol. The primary exposure variable is D3Cr muscle mass, examined as an absolute value in kilograms (kg) and relative to total body weight (D3Cr muscle mass/body mass in kg). Tertiles of absolute D3Cr muscle mass and D3Cr muscle mass/body mass were examined. The primary outcomes were objective measures of physical performance, including balance, gait speed, chair stands, and hand grip strength. The short physical performance battery (SPPB) provided an overall measure of physical performance. Physical function and functional limitation were assessed via self-report questionnaire. The association between D3Cr muscle mass/kg (in tertiles) and functional limitation was assessed in multivariate logistic regression analyses. Results The mean age of the study sample was 84.5 years. Average D3Cr muscle mass in the study population was 17.6 kg (SD = 4.0) and 26.1% (SD = 5.8). Mean SPPB scores were higher across higher tertiles of D3Cr muscle mass (7.0 in T1, 7.8 in T3). Women with low muscle mass were more likely to self-report prevalent limitation in physical function. Conclusion In this large cross-sectional study of older women, there was a strong relationship between low D3Cr muscle mass, physical performance, and functional limitation.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social, economic, and environmental disparities in device-measured 24-hour movement behaviours in a nationally representative cohort of older English adults","authors":"Laura Brocklebank, Andrew Steptoe, Mikaela Bloomberg, Aiden Doherty","doi":"10.1093/gerona/glag197","DOIUrl":"https://doi.org/10.1093/gerona/glag197","url":null,"abstract":"Background Insufficient physical activity, excessive sedentary time, and suboptimal sleep duration (i.e., not excessively short or long) are linked to morbidity and premature mortality and may contribute to health inequalities, but device-measured, nationally representative data capturing the full 24-hour movement spectrum remain scarce, particularly among older adults. This study examined social, economic, and environmental disparities in 24-hour movement behaviours in the 2021-23 English Longitudinal Study of Ageing (ELSA) accelerometry sub-study. Methods A subset of 5,382 ELSA participants (71.9%) was invited to wear a wrist accelerometer for eight days, with 4,354 (80.9%) agreeing. Raw data were processed using three distinct machine learning algorithms to estimate step count, sleep duration, moderate-to-vigorous and light physical activity, and sedentary time. Cross-sectional associations with sex, age, education, marital status, wealth, and urbanicity were examined using linear regression. Results Data from 3,648 participants (mean age 68.5 ± 9.3 years; 44.3% male) were included in the wear time analyses (median 6.6 days, IQR 6.0-6.9) and data from 3,161 (86.7%) participants with sufficient wear time were included in the 24-hour movement behaviour analyses. Older, unmarried, or lower education/wealth participants were less active, more sedentary, and slept less. Rural participants were more active than urban participants. Females accumulated fewer steps and less moderate-to-vigorous activity and sedentary time, but more light activity and longer sleep than males. Conclusions Social, economic, and environmental disparities exist across the full 24-hour movement spectrum, highlighting groups for targeted interventions. Follow-up will clarify how 24-hour movement behaviours influence healthy ageing and contribute to health inequalities.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modifiable Risk Factors for Mortality Across Life Course: A Pooled Population-Based Cohort Study","authors":"Shimin Chen, Shengshu Wang, Bin He, Shanshan Yang, Ke Han, Yueting Shi, Huaihao Li, Yinghui Bao, Junhan Yang, Wenchang Wang, Shengyan Du, Xiaoxin Ye, Yanhao Wan, Jianhua Wang, Yali Zhao, Yizhi Chen, Qiao Zhu, Chaoxue Ning, Yujian Chen, Shihui Fu, Xiangyang Zheng, Weisen Zhang, Lin Xu, Dianjianyi Sun, Miao Liu, Yao He","doi":"10.1093/gerona/glag196","DOIUrl":"https://doi.org/10.1093/gerona/glag196","url":null,"abstract":"Background China's rapid shift toward an aging society has revealed a critical knowledge gap regarding life-course modifiable risk factors associated with mortality, particularly within its rapidly expanding oldest-old population. Methods This pooled population-based cohort study analyzed 11 potential modifiable risk factors across life course (30-49, 50-59, 60-79, 80-99, ≥100 years), leveraging data from the China Kadoorie Biobank (CKB), the China Hainan Centenarian Cohort Study (CHCCS), and the Guangzhou Biobank Cohort Study (GBCS). The modifiable risk factor score was calculated as the sum of the number of risk factors present. Cox proportional hazards regression models, adjusted for age, sex, and all other modifiable risk factors, were conducted to assess the age-stratified associations in each cohort. Adjusted hazard ratios (HRs) and population attributable fractions (PAFs) were calculated for all-cause mortality. Results During a mean follow-up of 10.53 years in CKB (enrolled 2004-2008), 3.79 years in CHCCS (enrolled 2014-2016), and 13.20 years in GBCS (enrolled 2003-2008), the mortality rates were 6.45, 169.52, and 12.72 per 1,000 person-years among 29,679, 1,794, and 29,572 participants, respectively. An overall modifiable risk factor score was associated with elevated mortality risk spanning from middle-aged adults to centenarians, with HR (95% CI) ranging from 1.11 (1.01-1.21) to 1.31 (1.21-1.36). Metabolic risk factors showed attenuated association with mortality across life course: from 1.43 (1.14-1.80) in middle-aged individuals to 1.07 (0.99-1.17) in centenarians. Diabetes and hypertension dominated this risk cluster, with hypertension-attributable mortality peaking at 16.2% (8.3-22.6%) in presenium before diminishing to residual levels (0.6% and 0.1%) in advanced longevity groups. Conversely, low educational attainment exhibited progressively increasing mortality impacts with advancing age (HR:1.55 [1.13-2.14] to 1.74 [1.01-3.01]; PAF:6.4%-30.8%). A similar trend was observed for physical inactivity, which contributed significantly to mortality in both middle-aged individuals and centenarians. Conclusion Our life-course stratification reveals dynamic transitions in mortality risk, with metabolic burdens diminishing and socio-behavioral risks intensifying as longevity is achieved. These findings advocate for age-specific prevention strategies targeting dominant modifiable risk factors to optimize healthy aging trajectories.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbial load mediates the longevity effect of Korean red ginseng in Drosophila melanogaster","authors":"Wenting Gao, Hye-Yeon Lee, Kyung-Jin Min","doi":"10.1093/gerona/glag201","DOIUrl":"https://doi.org/10.1093/gerona/glag201","url":null,"abstract":"Korean red ginseng (KRG) has been reported to modulate gut microbiota and extend lifespan. However, whether the gut microbiota contributes to the longevity effect of KRG remains unclear. Here, using axenic flies and fecal microbiota transplantation, we showed that the lifespan-extending effect of KRG depends on the gut microbiota. Further analyses revealed that KRG exerted minimal effects on microbial diversity and composition, but significantly reduced microbial load. Moreover, gnotobiotic and antibiotic treatment experiments revealed that overall microbial load, rather than any individual dominant taxon, is the key mediator of KRG-mediated longevity. Mechanistically, KRG-mediated regulation of the canonical longevity pathways, IIS and Sir2, was dependent on microbial load. Specifically, the effects of KRG on AKT phosphorylation, FOXO nuclear translocation, and the expression of FOXO target genes and Sir2, observed in conventional flies, were abolished in axenic and antibiotic-treated flies. In addition, neither KRG nor antibiotic treatment extended lifespan in chico or Sir2 mutant flies, and KRG conferred no additional benefit in antibiotic-treated mutants. Collectively, these findings demonstrate that KRG extends lifespan by reducing gut microbial load, thereby modulating the IIS and Sir2 pathways, and highlight microbial load as a key mediator of KRG-induced longevity.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"346 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Napping, Sleep Apnea, and Cognitive Function: Cross-sectional Results from the U.S. POINTER-zzz Sleep Ancillary Study","authors":"Pankaja Desai, Marjorie Howard, Christine C Tangney, Katie L Stone, Susan Redline, Thomas M Holland, Shannon Halloway, Kaitlin Koncilja BA, Julissa A Santana, Rachel A Whitmer, Mark A Espeland, Kathleen M Hayden, Laura D Baker","doi":"10.1093/gerona/glag198","DOIUrl":"https://doi.org/10.1093/gerona/glag198","url":null,"abstract":"Background The relationship between the duration of napping and cognitive function is unclear. We examine this association by analyzing baseline data from the US POINTER-zzz Sleep Ancillary Study. Methods This study evaluates sleep assessments obtained via home apnea-screening device, wrist actigraphy, and sleep diaries among 686 older adult participants. Naps were defined as sleep periods with at least 30 continuous minutes outside of the primary period of sleep or the longest sleep duration. We conducted linear regression analyses to test the association between napping minutes and baseline global cognitive function and its domains, including executive function, episodic memory, and processing speed. We also examined whether the association between duration of napping and cognitive function outcomes differed by the presence (n = 223) or absence of sleep apnea (n = 463). Results For the total sample, greater minutes of napping were associated with decreased processing speed (β= - 0.0973 (95% CI= - 0.1664, -0.0282)). The interaction analyses between sleep apnea and napping did not reach statistical significance, providing no evidence that sleep apnea modifies the association between napping and cognition in the total sample. Greater minutes of napping were associated with poor executive function in participants with sleep apnea and who were in an under-represented ethno-racial group (β=-0.2493 (95% CI=-0.4943, -0.0042)). Conclusions Study findings are exploratory and suggest that it may be important to detect and treat sleep apnea for possible cognitive benefits, especially in certain subgroups of older adults.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148726428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perceived Fatigability and Fall Risk in Aging with and without Multiple Sclerosis: A Prospective Cohort Study","authors":"Di-Hua Luo, Roee Holtzer","doi":"10.1093/gerona/glag199","DOIUrl":"https://doi.org/10.1093/gerona/glag199","url":null,"abstract":"Background Fatigue and falls are prevalent and disabling in both aging and older adults with multiple sclerosis (OAMS). However, clinically useful, modifiable predictors of fall risk remain insufficiently established. Perceived fatigability has been shown to cross-sectionally correlate with poorer cognitive and mobility outcomes in normative aging and OAMS, but its prospective relationship with falls is unclear. We examined whether baseline perceived fatigability predicts falls during longitudinal follow-up in community-dwelling older adults with and without MS. Methods Participants were 223 older adults aged ≥60 years (109 OAMS; 114 healthy controls). Baseline physical and mental fatigability were assessed using the Pittsburgh Fatigability Scale (PFS). Falls were prospectively tracked using structured monthly telephone interviews during the study period (from September 2019-April 2025). Generalized estimating equations estimated fall risk, adjusting for demographic and clinical covariates, including prior falls. Results In the full cohort, higher physical (OR = 1.54, 95%CI=1.25-1.91, p<0.001) and mental fatigability (OR = 1.41, 95%CI=1.12-1.77, p=0.004) were each associated with greater odds of falls after covariate adjustment. Physical fatigability remained significant after accounting for group status (OR = 1.37, 95%CI=1.09-1.71, p=0.006). Mental fatigability was attenuated after inclusion of group status. Group status did not significantly moderate the fatigability-fall risk associations (p-values >0.05 for all interactions between fatigability and group status). Conclusions Worse perceived physical and mental fatigability were associated prospectively with increased fall risk in both OAMS and healthy controls. These findings support the potential clinical utility of fatigability assessment for fall-risk profiling and for informing more tailored fall prevention strategies in normative and MS-related aging.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking Epigenetic Age Acceleration to Self-Reported Daily Memory Lapses: Evidence from the National Study of Daily Experiences","authors":"Heejung Jang, Jennie C Holmberg, Jody S Nicholson, Faith R Shannon, Eric S Cerino, Hye Won Chai, Susan T Charles, David M Almeida","doi":"10.1093/gerona/glag202","DOIUrl":"https://doi.org/10.1093/gerona/glag202","url":null,"abstract":"DNA methylation algorithms, such as DunedinPACE (1), are increasingly used to study the mechanisms of aging and to identify associations with risk factors in adult development and aging. Growing evidence suggests that an increased pace of epigenetic aging is associated with cognitive impairment and dementia (2), but the correlation between epigenetic aging and subjective cognitive complaints (e.g., forgetting a name or forgetting to take your medication), an early marker of dementia risk, remains unexplored. Using data from The National Study of Daily Experiences (NSDE) and Midlife in the United States (MIDUS; N = 232), we examined the relationship between epigenetic aging rate (i.e., DunedinPACE) and self-reported daily memory lapses (i.e., occurrence, irritation, interference) in midlife and older adults. We found no significant main effects of the rate of epigenetic aging on self-reported memory lapses; however, a significant chronological age interaction indicates that among the comparatively younger adults in the sample (age 40-49), faster than average rates of aging (i.e., higher DunedinPACE) were associated with more prospective memory lapses approximately a decade later as well as greater reports of prospective memory lapse irritation and interference. Additionally, for respondents in their forties, a higher DunedinPACE was associated with both greater prospective memory lapse irritation and interference. These results suggest that early midlife may be a sensitive period during which the rate of epigenetic aging is more influential on cognitive health outcomes.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic and functional study of lncRNA SNHG3/miR-128-3p/UBR5 axis in neuroinflammation in Alzheimer's disease","authors":"Xin-An Zhu, Huijie Lu, Yumei Liu, Xianlei Xue, Liangfeng Lin","doi":"10.1093/gerona/glag187","DOIUrl":"https://doi.org/10.1093/gerona/glag187","url":null,"abstract":"Neuroinflammation assumes a pivotal role in Alzheimer's disease (AD) pathogenesis. Long noncoding RNAs (lncRNAs) regulate neuroinflammation through a competitive endogenous RNA (ceRNA) mechanism. This study aimed to explore the mechanism of SNHG3/miR-128-3p/UBR5 axis in AD associated neuroinflammation. SNHG3, miR-128-3p, and UBR5 levels were recognized by reverse transcription - quantitative polymerase chain reaction (RT-qPCR). In vitro AD model was established by Aβ1-42 stimulation in human microglial cells HMC3 and neuronal cells SK‑N‑SH. Cell apoptosis was detected by flow cytometry. Enzyme - linked immunosorbent assay (ELISA) and oxidative stress indicators were used to evaluate the neuroinflammatory phenotype. Morris water maze (MWM) test assesses the spatial learning and memory abilities of amyloid precursor protein/presenilin 1 (APP/PS1) mice with AAV-si-SNHG3. Serum SNHG3 was clearly upregulated in AD patients, and negatively related to MMSE score (r = -0.691, P<0.001). SNHG3 had diagnostic potential for AD (AUC=0.847, 95% CI = 0.806-0.888, sensitivity=75.63%, specificity=76.88%). SNHG3 regulates UBR5 expression by sponges miR-128-3p. Silence of SNHG3 inhibited M1 polarization (reducing TNF-α, IL-6, and iNOS), promotes M2 polarization (increasing Arg1, IL-10, and TGF-β), inhibits IL-1β release, suppresses neuronal apoptosis, and mitigates oxidative stress damage (reducing MDA and increasing SOD) via miR-128-3p/UBR5 axis in Aβ-stimulated HMC3 cells. SNHG3 also contributes to Aβ‑induced neuronal apoptosis, inflammation, and oxidative stress in SK‑N‑SH cells. AAV-si-SNHG3 significantly enhances spatial learning and memory abilities of APP/PS1 mice, and inhibits neuroinflammation and oxidative stress in the hippocampus. This study is the first to elucidate that SNHG3 could regulate microglial polarization and neuroinflammation through the SNHG3/miR-128-3p/UBR5 axis.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relationship between parity and late-life frailty: companion dogs as a preclinical model for evaluating factors that aggravate or mitigate the frailty cost of reproduction","authors":"David J Waters, Aimee H Maras, Rong Fu, Andres E Carrillo, Emily C Chiang, Cheri L Suckow","doi":"10.1093/gerona/glag163","DOIUrl":"https://doi.org/10.1093/gerona/glag163","url":null,"abstract":"Frailty refers to a state of heightened vulnerability to adverse health outcomes. Animal models of frailty provide an opportunity to probe lifetime events and exposures that drive frailty progression and to evaluate intervention strategies that could mitigate frailty development and its consequences in older adults. The relationship between parity—production of live offspring—and later life frailty in women is poorly understood. Here, we utilize companion dogs to test the hypothesis that production of live offspring comes at a physiological cost, leading to increased late-life frailty. We measured deficit accumulation using a 34-item clinical frailty index in a cohort of 95 geriatric female Rottweilers. The study outcome was late-life robustness, defined as the lowest quintile of frailty in the study population. We found no evidence of reproductive cost. Instead, compared to nulliparous females, parous females were 3× more likely to retain late-life robustness [OR, 95% CI = 3.30,1.16-9.38; p = .025], a relationship not attenuated by adjusting for covariates, including owner-reported reason for nulliparity. Moreover, females with largest number of litters had highest late-life robustness. Finally, employing two measures of early-life health/fitness—earlier-in-life health deficits, lifetime morbidity profiles—could not explain results based on selection. This inquiry introduces a new application of the dog model of frailty for the study of reproduction and deficit accumulation. The linkage we observed between parity and higher late-life robustness is congruent with results of several studies in women, suggesting parous females may have the capacity to dampen the development of later-in-life frailty, which should be further investigated at the genetic and epigenetic level.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148522444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}