The journals of gerontology. Series A, Biological sciences and medical sciences最新文献

{"title":"Treatment completion rate, toxicity, and 90-Day unplanned readmission in older adults with esophageal squamous cell carcinoma receiving radiotherapy alone versus concurrent chemoradiotherapy.","authors":"Junyu Xie, Longzhen Zhang, Ye Yuan, Xundong Yan, Yongxiang Wang, Shufan Li, Xuejing Yu","doi":"10.1093/gerona/glag123","DOIUrl":"10.1093/gerona/glag123","url":null,"abstract":"<p><strong>Background: </strong>The optimal treatment for older adults (≥70 years) with esophageal squamous cell carcinoma (ESCC) remains controversial, with limited evidence comparing radiotherapy (RT) alone versus concurrent chemoradiotherapy (CCRT).</p><p><strong>Methods: </strong>We conducted a single-center, retrospective, target trial emulation study of 432 patients aged ≥70 years with ESCC who received definitive RT (n = 214) or CCRT (n = 218) between 2016 and 2024. The primary outcome was treatment completion rate, defined as receipt of prescribed radiation dose for RT, and additionally achieving a relative dose intensity ≥80% for chemotherapy in the CCRT group. Key secondary outcomes included grade ≥3 toxicity and 90-day unplanned readmission. Inverse probability of treatment weighting was used to adjust for confounding.</p><p><strong>Results: </strong>After adjustment, CCRT was associated with significantly lower treatment completion rates compared to RT (adjusted risk ratio [aRR] 0.86, 95% CI, 0.79-0.93; absolute risk difference -13.5%). CCRT demonstrated higher rates of grade ≥3 toxicity (38.1% vs 17.8%; aRR 2.01), grade 4 toxicity (8.7% vs 2.3%; aRR 3.55), and 90-day readmission (21.6% vs 12.6%; aRR 1.72). RT completion alone was also lower with CCRT (80.3% vs 88.3%; RR 0.91). Short-term tumor response was numerically higher with CCRT, at the cost of significantly increased toxicity. Effects were more pronounced in patients aged ≥75 years, those with Charlson Comorbidity Index ≥6, and frail patients (G8 ≤ 14).</p><p><strong>Conclusions: </strong>In this real-world cohort of older adults with ESCC, CCRT was associated with significantly lower treatment completion rates and higher toxicity and readmission rates compared to RT alone. These findings highlight the importance of careful patient selection and shared decision-making when considering treatment intensification in older adults with ESCC.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148274462","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":"Cluster randomized trial of reablement strategies targeting sarcopenia (ReStart-S) in long-term care settings.","authors":"Prabal Kumar, Shashikiran Umakanth, Kusumakshi Nayak, Olivier Bruyère, Vennila Jaganathan, Girish Nandakumar","doi":"10.1093/gerona/glag141","DOIUrl":"10.1093/gerona/glag141","url":null,"abstract":"<p><strong>Background: </strong>Sarcopenia prevalence is high in long-term care settings (LTCS), yet existing guidelines often overlook this population. The Reablement Strategies targeting Sarcopenia (ReStart-S) program was developed to address this gap. This study evaluated its effects on muscle outcomes, physical performance, quality of life (QoL), and a blood biomarker.</p><p><strong>Methods: </strong>A cluster-randomized trial was conducted in LTCS across Udupi and neighboring districts. Sarcopenic older adults (≥ 60 years, Barthel Index ≥ 60, Mini-Cog ≥ 3, AWGS-2019 criteria) were recruited. LTCS were randomized into intervention (IG) and control (CG) groups. IG received a 6-week ReStart-S program, while CG continued usual activities. Outcomes at baseline, 6, 12, and 18 weeks included handgrip strength (HGS, primary outcome), skeletal muscle index (SMI), Short Physical Performance Battery (SPPB), SarQoL, and C-terminal Agrin Fragment (CAF; not assessed at 12 weeks). Linear mixed models evaluated group*time interactions with Bonferroni correction.</p><p><strong>Results: </strong>Of 12 LTCS screened, 7 were eligible; 78 participants enrolled (IG = 39; CG = 39). CG was older than IG (74.3 ± 9.4 vs 67.9 ± 6.0; p < .001). Significant group*time interaction was observed for HGS (F = 5.524; p = .001), improving at 12 (2.49; 95% CI, 1.16-3.82; p < .001) and 18 weeks (2.14; 0.79-3.48; p = .002). SPPB improved at 6, 12, and 18 weeks (all p < .001). SarQoL improved at all follow-ups (all p < .001). SMI improved at 18 weeks (0.20; p = .011). CAF decreased at 18 weeks (-61.77; p < .001).</p><p><strong>Conclusion: </strong>ReStart-S improved muscle strength, physical performance, and QoL, reduced CAF, and showed delayed muscle mass gains, supporting its role in sarcopenia care in LTCS.</p><p><strong>Clinical trial registration: </strong>The study was prospectively registered on October 20, 2022 on the Clinical Trial Registry-India (CTRI) platform. Trial registration number CTRI/2022/10/046680. The trial can be accessed at: https://ctri.nic.in/Clinicaltrials/showallp.php? mid1=71007&EncHid=&userName=CTRI/2022/10/046680.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13287990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148140265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between age-related musculoskeletal diseases and Parkinson disease: a population-based cohort study of UK Biobank.","authors":"Tianmi Yang, Jingxuan Huang, Yi Xiao, Dejiang Pang, Yiyuan Cui, Yangfan Cheng, Chunyu Li, Qianqian Wei, Huifang Shang","doi":"10.1093/gerona/glag151","DOIUrl":"10.1093/gerona/glag151","url":null,"abstract":"<p><strong>Background: </strong>Age-related musculoskeletal diseases (ARMDs), including sarcopenia, osteoporosis, and osteoarthritis, may contribute to declines in intrinsic capacity and co-occur with neurodegenerative disorders such as Parkinson disease (PD). We examined the association between ARMDs and PD risk.</p><p><strong>Methods: </strong>In 362 656 UK Biobank participants (mean age: 56.48 years; median follow-up 13.65 years), ARMDs were assessed individually and cumulatively. Cox models estimated PD risk, adjusting for demographic, lifestyle, and genetic factors. Subgroup and sensitivity analyses were conducted to ensure robustness. A nested case-control analysis further explored the relationship between the duration of ARMDs exposure and the odds of PD diagnosis. Multivariable regression models assessed the associations between ARMDs and brain structure, including cortical, gray matter, and white matter integrity.</p><p><strong>Results: </strong>During follow-up, 2057 participants developed PD. Sarcopenia (hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.45-2.08, p < .001) and osteoporosis (HR: 1.76, 95% CI: 1.34-2.32, p < .001) were independently associated with higher PD risk. PD risk increased with the number of ARMDs (HR: 1.30, 95% CI 1.19-1.41; ptrend < .001) and the odds of PD diagnosis was highest within 5 years of the ARMDs diagnosis (odds ratio [OR] 2.19, 95% CI: 1.59-2.96, p < .001). Neuroimaging analysis indicated that ARMDs were associated with widespread and significant brain structural alterations, including in regions related to motor control.</p><p><strong>Conclusions: </strong>ARMDs are linked to elevated PD risk and brain structural changes. Interventions targeting musculoskeletal health may help preserve intrinsic capacity and delay or prevent PD onset in aging populations.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148177495","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":"Synergistic impact of rest-activity circadian rhythms and physical activity on all-cause and cardiovascular mortality.","authors":"Baichuan Gu, Haoyu Zhang, Ming Yi, Jin Si, Keling Xiao, Lijie Sun, Jinghao Sun, Huan Zhao, Ou Zhao, Yixin Ma, Hongyu Luo, Jing Li","doi":"10.1093/gerona/glag130","DOIUrl":"10.1093/gerona/glag130","url":null,"abstract":"<p><strong>Background: </strong>This study investigated the independent and joint associations of rest-activity circadian rhythms (RACRs) and physical activity (PA) with all-cause and cardiovascular mortality, and explored the potential role of accelerated biological aging.</p><p><strong>Methods: </strong>We included 6621 adults from NHANES 2011-2014. RACR parameters were derived from wrist-worn ActiGraph GT3X+ data. Accelerated biological aging was assessed using Phenotypic Age Acceleration (PhenoAgeAccel) and Biological Age Acceleration (BioAgeAccel). Cox proportional hazards models were applied to investigate the associations of RACRs and PA with all-cause and cardiovascular mortality. Exploratory mediation analyses were used to explore the associations between accelerated biological aging, RACRs, and mortality risks.</p><p><strong>Results: </strong>Over a median follow-up of 6.75 years, 518 all-cause deaths and 165 cardiovascular deaths were recorded. Compared with weak RACRs and inadequate PA, participants with strong RACRs and adequate PA had significantly lower risks of all-cause mortality (HR: 0.35, 95% CI: 0.24 to 0.51; p < .001) and cardiovascular mortality (HR: 0.25, 95% CI: 0.14 to 0.45; p < .001). In exploratory analyses, PhenoAgeAccel accounted for an estimated 13.55% (p < .001) and 21.67% (p = .002) of the associations between RACRs and all-cause and cardiovascular mortality, respectively, while BioAgeAccel accounted for an estimated 5.06% (p < .001) and 8.06% (p = .004).</p><p><strong>Conclusions: </strong>Disrupted RACRs are associated with higher mortality risks that could be attenuated by adequate physical activity. Exploratory analyses suggest that the associations between RACRs and mortality may be mediated in part by accelerated biological aging, but additional studies are needed to test this hypothesis.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147990031","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":"Evaluating the predictive utility of European-based and transethnic polygenic risk scores for kidney function in older Black adults: insights from the Health and Retirement Study.","authors":"Ryon J Cobb, Roland J Thorpe, Keith C Norris","doi":"10.1093/gerona/glag122","DOIUrl":"10.1093/gerona/glag122","url":null,"abstract":"<p><strong>Background: </strong>Black populations in the U.S. experience a disproportionately faster progression of chronic kidney disease than the general population. Polygenic risk scores (PRS) are a promising tool for risk stratification, yet their utility in predicting kidney function across populations remains uncertain.</p><p><strong>Methods: </strong>This study evaluates the effectiveness of European and trans-ethnic PRS in predicting kidney function among older Black adults from the 2010-2012 Health and Retirement Study (HRS) (N = 2080), a nationally representative sample of adults aged ≥50 years in the U.S. We assessed kidney function using an estimated glomerular filtration rate derived from cystatin C. The HRS constructed PRS from genome-wide association studies based on European and trans-ethnic ancestries. We used ordinary least-squares regression to examine the predictive power of European-based and transethnic PRS on kidney function, adjusting for demographic, behavioral, cardiometabolic risk, and socioeconomic factors.</p><p><strong>Results: </strong>The mean kidney function is approximately 74 mL/min/1.73 m2, with a wide range, indicating significant heterogeneity among older Black adults. Findings suggest that neither the European nor the trans-ethnic PRS demonstrated a significant association with kidney function in demographic-adjusted models among older Black adults. Including behavioral, cardiometabolic, and socioeconomic factors did not change this relationship.</p><p><strong>Conclusions: </strong>Our findings underscore the challenges of applying PRS to predict kidney function among older Black adults. They also emphasize the need for more inclusive genomic research and the significant impact of clinical and sociodemographic factors on kidney function among older Black adults. These insights are vital for enhancing precision medicine and ensuring equitable genomic practices.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147990648","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":"Plasma myeloperoxidase predicts cognitive decline in mild cognitive impairment: a multicenter longitudinal cohort study.","authors":"Wenxian Sun, Aidi Shan, Pin Wang, Xiaodong Han, Chang Xu, Heya Luan, Shaoqi Li, Cuibai Wei","doi":"10.1093/gerona/glag135","DOIUrl":"10.1093/gerona/glag135","url":null,"abstract":"<p><p>Mild cognitive impairment (MCI) is a key stage for early intervention in dementia, and its inflammatory mechanisms remain unclear. Myeloperoxidase (MPO), a key enzyme involved in inflammation and immune regulation, has not been fully studied in MCI. This multicenter longitudinal cohort study prospectively followed 133 patients with MCI for 12 months. Plasma MPO, Alzheimer's disease (AD)-related biomarkers (p-Tau181, p-Tau217, glial fibrillary acidic protein , neurofilament light chain, and Aβ42/40), inflammatory cytokines (IL-1β, IL-6, and TNF-α), neuropsychological performance, and APOE genotype were assessed at baseline and follow-up. During follow-up, 58 patients showed cognitive deterioration and 75 remained non-deteriorated. At both baseline and the 12-month follow-up, the cognitive deterioration group showed higher MPO, IL-1β, and IL-6 levels than the non-deterioration group. Within-group longitudinal changes from baseline to follow-up were modest and were not statistically significant. Cross-sectional analyses showed that MPO was associated with IL-1β, IL-6, Aβ42/40, Mini-Mental State Examination (MMSE), and Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) at different assessment time points. Longitudinal delta analyses showed that changes in MPO were significantly correlated with changes in MMSE, IL-1β, and IL-6, but not with changes in ADAS-Cog or Aβ42/40. After adjustment for potential confounders, MPO remained an independent predictor of cognitive deterioration in MCI (OR = 1.018, 95% CI, 1.00-1.03, p = .015). Nomogram analysis showed that MPO was the most prominent predictor in the model. These findings suggest that elevated plasma MPO may serve as a clinically accessible prognostic biomarker for risk stratification in patients with MCI.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148007727","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":"Interventions that prolong multidimensional healthspan in humans: a systematic review of randomized controlled trials.","authors":"Haoxin Tina Zheng, Aung Zaw Zaw Phyo, Claire McCubbin, Zimu Wu, Heike A Bischoff-Ferrari, Joanne Ryan","doi":"10.1093/gerona/glag133","DOIUrl":"10.1093/gerona/glag133","url":null,"abstract":"<p><p>Maximizing healthspan, the period of life spent in good health, is a public health priority. This review aimed to summarize the current evidence from randomized controlled trials on interventions that can prolong healthspan in humans. The specific focus was on multidimensional person-centered outcomes, which reflect functioning rather than disease, such as intrinsic capacity and quality of life. This review was registered (CRD420251015780) and conducted with adherence to the PRISMA guidelines. MEDLINE, EMBASE, and grey literature were systematically searched for studies evaluating interventions that improve intrinsic capacity or quality of life. The search included articles published up to October 16, 2025. Of 1960 publications identified, 15 articles (4656 participants) met the inclusion criteria. There was high heterogeneity between the included studies in terms of the interventions examined, which varied from exercise alone (7 studies) to multidomain interventions (6 studies, all of which included an exercise component), daily oral supplementation (2 studies), or caloric restriction (1 study). Overall, 11 studies reported that exercise or multidimensional intervention (which included an exercise component) improved intrinsic capacity and quality of life. However, due to the small number of studies and heterogeneity, no conclusion could be drawn regarding other interventions. Therefore there is some evidence that exercise could extend intrinsic capacity and quality of life, either aerobic or resistance training alone, or a combination of different types of exercise; but further research is required to evaluate the effect of other interventions that may prolong healthspan across more diverse populations.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13290488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148007742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of an electronic health record-based frailty index in the UK Biobank.","authors":"Grace I Bowman, Nigel Seymour, Chandra Reynolds, Luke M Evans","doi":"10.1093/gerona/glag131","DOIUrl":"10.1093/gerona/glag131","url":null,"abstract":"<p><strong>Background: </strong>Frailty, an age-related loss of the ability to withstand stressors, is commonly measured using health deficit indices, often using survey or questionnaire data. We aimed to develop an electronic frailty index (eFI) using electronic health record (EHR) data linkages in the UK Biobank and assess its association with mortality.</p><p><strong>Methods: </strong>We calculated an eFI using 43 deficits, each corresponding to phecodes mapped to the United Kingdom (UK) and international classification coding systems. We compared this eFI to a validated 49-item survey-based FI for the UK Biobank (UKB) and assessed associations of the eFI with risk of all-cause mortality (follow-up ≤ 10.2 years) and mortality following a stressor (heart attack or stroke) using Cox proportional hazard models.</p><p><strong>Results: </strong>Mean eFI in this cohort (N = 208,982) was 0.058 (SD = 0.06) and was higher in females than males. A 10% higher baseline frailty was associated with higher risk of all-cause mortality (HR (95% CI)=2.00 (1.93-2.07)), although the magnitude of this association decreased when adjusting for socioeconomic-related covariates (HR (95% CI)=1.44 (1.38-1.51)). Associations were stronger in men than women. Electronic frailty index predicted mortality following both heart attack and stroke (HR (95% CI) = 1.59 (1.25-2.04) and HR = 1.33 (1.13-1.57), respectively).</p><p><strong>Conclusions: </strong>This EHR-based eFI has robust associations with mortality, suggesting that it can be used as a valid measure of frailty in the UKB and can potentially be applied to other datasets with EHR data.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147990655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Association of heatwave exposure and multimorbidity with depression trajectories among older adults: evidence from the China Health and Retirement Longitudinal Study.","authors":"","doi":"10.1093/gerona/glag161","DOIUrl":"https://doi.org/10.1093/gerona/glag161","url":null,"abstract":"","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":"81 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148355298","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":"Evidence for an energy conservation model of inflammaging and immunosenescence in the US Health and Retirement Study and UK Biobank.","authors":"Jacob E Aronoff, Maximilien Franck, Alan A Cohen, Benjamin C Trumble","doi":"10.1093/gerona/glag119","DOIUrl":"10.1093/gerona/glag119","url":null,"abstract":"<p><p>The development of chronic inflammation in later life (inflammaging), alongside changes in immune cell profiles and impaired pathogen defense (immunosenescence), contribute to health risk. However, these processes have been hypothesized as adaptive remodeling of the immune system in response to accumulating somatic damage. Here we consider a recently developed theoretical framework to understand their relationship: the Brain-Body Energy Conservation model of aging. This model views immunosenescence as part of an energy conserving response to the rising energy expenditure of inflammaging. This response promotes short-term survival against somatic damage at the expense of future health risk. For example, naïve T cells, which enhance defense against future infections, decline with age, while proteins that suppress the immune response to infection, including interleukin (IL)-10, increase. GDF-15, which similarly suppresses the immune response to infection and is produced in response to chronic inflammation and metabolic stress, also increases with age. We find evidence consistent with this model in the US Health and Retirement Study (HRS, n = 8 184) and UK Biobank (UKB, n = 40 510). Across both cohorts, the key inflammaging marker tumor necrosis factor receptor (TNFR1) partially mediated the age-related increases in IL-10 and GDF-15. In the HRS flow cytometry data, TNFR1 also mediated age-related decreases in naïve T cells. Finally, we assessed vulnerability to a novel future infection using the UKB medical records data on hospitalization or death from COVID-19 (n = 586 hospitalized or died). TNFR1, IL-10, and GDF-15, measured pre-pandemic, all partially mediated the age-related increased risk.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13275305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}