The Journals Of Gerontology. Series A, Biological Sciences And Medical Sciences[JOURNAL]
Sun
200 papers
Adolescent Dietary Restriction Improves Cognition and Frailty in Aged Female Wistar Rats.
Simeunovic V, Mladenovic A, Prvulovic M … +3 more , Jovic M, Pracer S, Sokanovic S
J Gerontol A Biol Sci Med Sci · 2026 Jul · PMID 42398023 · Publisher ↗
Dietary restriction (DR) is the most studied non-pharmacological intervention for extending both lifespan and healthspan. While previously considered universally beneficial, recent findings indicate that the effects of D...
Dietary restriction (DR) is the most studied non-pharmacological intervention for extending both lifespan and healthspan. While previously considered universally beneficial, recent findings indicate that the effects of DR depend on its onset and duration. Although frequently practiced among teenage girls, the effects of DR in this developmental period remain insufficiently investigated, and existing conclusions are scarce. This study aims to determine the short- and long-term effects of mild adolescent DR on the behavior and frailty in aging female Wistar rats. Female Wistar rats were fed ad libitum (AL) or were dietary restricted (70% of AL daily intake) during early adolescence (EADR), middle adolescence (MADR), or both early and middle adolescence (EMADR). Short-term effects were examined using the Open Field (OF) and Y-maze tests, while long-term effects were assessed using OF, Y-maze, and Novel Object Recognition (NOR) tests, along with survival rate and frailty assessments. Long-term effects on cortical synaptic markers were examined by analyzing the expression of synaptophysin (SPH), drebrin, postsynaptic density protein 95 (PSD95), and phosphorylated PSD95 (p-PSD95). Despite the absence of early behavioral effects, predominantly beneficial effects on survival, behavior, frailty, followed by changes in synaptic proteins have been noticed at old age. Our results showed onset- and duration-dependent effects of adolescent DR on aged animals. This study is the first to evaluate the lifelong effects of adolescent DR and highlights the importance of early nutritional habits and the need for caution in dietary interventions during critical developmental stages.
Frailty, polypharmacy, deprescribing and 23-hour activity: insights from a mouse model.
Mach J, Winardi K, Hilmer SN
J Gerontol A Biol Sci Med Sci · 2026 Jul · PMID 42391622 · Publisher ↗
Management of older people with frailty commonly includes polypharmacy and deprescribing. The impacts of frailty on the outcomes of medication use and deprescribing are poorly understood; as are the effects of medication...
Management of older people with frailty commonly includes polypharmacy and deprescribing. The impacts of frailty on the outcomes of medication use and deprescribing are poorly understood; as are the effects of medication use and deprescribing on frailty and function. Here, using aged C57BL/6J (B6) male mice, we explore the effects of different chronic drug regimens (polypharmacy and monotherapy) and deprescribing on daily activities using an automated behavioral recognition cage, and explore the relationship with frailty and trajectories. At 12 months, male C57BL/6 mice were chronically administered control diet, one of 5 monotherapy diets or one of 3 polypharmacy diets with an increasing Drug Burden Index (measure of total exposure to sedative and anticholinergic medications). At 21 months of age, mice were stratified to continue treatment or to have treatment gradually withdrawn (deprescribed). At 24 months, mice were assessed using the LABORAS automated animal behavioral recognition system for 23 hours. We found that polypharmacy with increasing DBI substantially altered activity and could not be extrapolated from monotherapy response. After deprescribing, while some of the drug effects were reversible, others were irreversible, and we observed some novel changes. Exploring the relationship between frailty and LABORAS behavioral outcomes revealed unique correlations for each intervention group. Four key clusters were identified with different frailty trajectories and attributes, deficits and LABORAS outcomes. This preclinical study demonstrates that medication use and deprescribing can impact activity, frailty and frailty trajectories. The context of polypharmacy and deprescribing are important considerations to enhance translation of pre-clinical studies of frailty.
The Contribution of Social and Economic Factors to Accelerated Biological Aging Differences Between Non-Hispanic Black and White Adults in the Health and Retirement Study.
Abugroun A, Neilands TB, Livaudais-Toman J … +3 more , Johnson JK, Karliner L, Fang MC
J Gerontol A Biol Sci Med Sci · 2026 Jul · PMID 42391611 · Publisher ↗
BACKGROUND: Biological aging predicts health outcomes beyond chronological age. The relative contribution of social, economic, and health factors to biological aging differences between Black and White adults remains unc...
BACKGROUND: Biological aging predicts health outcomes beyond chronological age. The relative contribution of social, economic, and health factors to biological aging differences between Black and White adults remains unclear. METHODS: In a cross-sectional analysis of 2,086 community-dwelling adults aged ≥60 years from the 2016 Health and Retirement Study (1,757 non-Hispanic White; 329 non-Hispanic Black), biological age was measured using DNA methylation-based GrimAge. Accelerated aging was defined as having a biological age older than expected for one's chronological age. We used logistic regression to assess the impact of race on accelerated aging and decomposition analysis to determine factors explaining differences in accelerated aging between Black and White participants. Covariate blocks were: age, education, wealth, social frailty assessed using a composite index measuring social connections, financial autonomy, neighborhood environment, volunteering and employment engagement, behavioral factors (physical activity, alcohol use, sleep disorder, body mass index); medical conditions; and physical disability. RESULTS: Black participants had higher accelerated aging than White participants (57.1% vs 41.8%; standardized mean difference, 0.3). In the staged decomposition of the biological aging gap, age and education explained 21.1% of the difference. The cumulative explained share rose to 51.8% with wealth, 77.6% with social frailty, 80.3% with health behaviors, 90.5% with medical conditions, and 91.6% with physical disability. In multivariable logistic regression adjusting for all domains, the racial difference was no longer significant. CONCLUSIONS: Social and economic factors largely explained accelerated biological aging differences between non-Hispanic Black and White adults. These findings identify policy-relevant targets to improve healthy aging.
Longitudinal changes in radiomic features of skeletal muscle on CT images with changes in muscle strength and physical performance in older adults.
Hetherington-Rauth M, Mansfield TA, Weaver AA … +2 more , Lenchik L, Cawthon PM
J Gerontol A Biol Sci Med Sci · 2026 Jul · PMID 42391051 · Publisher ↗
BACKGROUND: Skeletal muscle health is a key determinant of aging, independence, and disease outcomes. Traditional computed tomography (CT)-derived measures of muscle cross-sectional area (CSA) and density reflect muscle...
BACKGROUND: Skeletal muscle health is a key determinant of aging, independence, and disease outcomes. Traditional computed tomography (CT)-derived measures of muscle cross-sectional area (CSA) and density reflect muscle quantity and quality but may not capture structural heterogeneity relevant to functional decline. Radiomics, a CT image analysis approach, enables extraction of high-dimensional texture features, offering additional insight into muscle quality. While muscle radiomics have been associated with strength and mobility in older adults, longitudinal applications remain understudied. We examined whether 5-year changes in thigh muscle radiomic features were associated with changes in muscle strength and performance in the Health, Aging, and Body Composition Study. METHODS: Thigh CT scans from 1321 older adults were analyzed using automated muscle segmentation to quantify CSA, density, and extract radiomic features. Strength measures included grip strength and maximal isokinetic knee extension; performance measures included 20-m walking speed, 5-time chair stands, and a modified performance score. Factor analysis reduced radiomic features to seven latent factors. Nested linear mixed-effects models tested associations of muscle CSA and density with outcomes, with and without radiomic factors. RESULTS: Factors 2 and 5 were consistently associated with 5-year changes across muscle outcomes. Factor 2 (high pixel gray-level intensity and uniformity) was positively associated, whereas Factor 5 (pixel clustering asymmetry and heterogeneity) was inversely associated. Adding radiomic factors modestly improved model fit (p < 0.05), explaining 1-2% additional variation in performance. CONCLUSION: Longitudinal changes in thigh muscle radiomics capture subtle compositional characteristics beyond muscle CSA or density, enhancing understanding of functional decline with aging.
Correction to: Association of heatwave exposure and multimorbidity with depression trajectories among older adults: evidence from the China Health and Retirement Longitudinal Study.
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42373573 · Publisher ↗
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The association of frailty with age and lifespan in mice differs by strain and sex.
Zhu D, Green CL, Mitchell SJ … +15 more , Macarthur MR, Bisset ES, Mach J, Wu JZ, Samuelson BA, Shindyapina A, Moldakozhayev A, Tskhay A, Tyshkovskiy A, Gladyshev VN, Sinclair DA, Howlett SE, Hilmer SN, Lamming DW, Kane AE
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42363413 · Publisher ↗
Frailty indices have been assessed in mouse models for more than a decade, but the effect of sex and strain on frailty outcomes remains poorly understood. Here, we collated and harmonized item-level 31-item clinical frai...
Frailty indices have been assessed in mouse models for more than a decade, but the effect of sex and strain on frailty outcomes remains poorly understood. Here, we collated and harmonized item-level 31-item clinical frailty index (FI) and lifespan data from 17 independent cohorts, including 1,564 naturally aging mice (690 females, 874 males) across five commonly used mouse strains or substrains: C57BL/6JNIA, C57BL/6N, C57BL/6J, UM-HET3, and Diversity Outbred. A total of 3,665 observations were included across cross-sectional and longitudinal studies, some previously published, with 2,192 observations linked to known age at death. Across all cohorts, FI increased significantly with chronological age, but the rate of frailty accumulation differed by strain. Sex differences in age-associated frailty trajectories were evident only in C57BL/6JNIA mice. Significant strain- and sex-specific differences in both survival and healthspan were observed, with males generally outliving females, although sex effects varied by strain. FI was strongly associated with lifespan independent of age, although age-dependent effects emerged in specific strains with notable sex-specific patterns. At the level of individual frailty items, most health deficits showed strain-dependent associations with age and lifespan. Collectively, these findings demonstrate that the relationships between frailty, chronological age, and lifespan are strongly modulated by strain and sex. This work highlights the importance of accounting for strain and sex as factors when investigating and utilizing frailty in preclinical models.
Association between Hearing Loss, Physical Activity, and Sedentary Behavior: A Nationally Representative Cross-Sectional Study in Chile.
Morales C, Martinez-Amezcua P, Caballero FF … +4 more , Oliveros MJ, Seron P, Lopez-Garcia E, Yévenes-Briones H
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42363407 · Publisher ↗
BACKGROUND: Hearing loss is common in midlife and older adults and may constrain communication and participation, potentially shaping physical activity and sedentary time; however, population-based evidence remains incon...
BACKGROUND: Hearing loss is common in midlife and older adults and may constrain communication and participation, potentially shaping physical activity and sedentary time; however, population-based evidence remains inconsistent. METHODS: We analyzed a nationally representative sample of Chilean adults aged ≥40 years from the 2016-2017 Chile National Health Survey (n = 3512). Hearing loss was defined by a "no" response to any of three self-report items. Global Physical Activity Questionnaire outcomes included overall physical activity (high/moderate/low), domain-specific energy expenditure (work, transport, leisure; MET-hours/week), and high sedentary behavior (≥8 h/day). We fitted survey-weighted ordinal, gamma (log link), and logistic regression models; effect modification by sex, age, and sleep quality was tested. Sensitivity analyses used inverse probability-of-exposure weighting with gradient-boosted propensity scores. RESULTS: The weighted prevalence of hearing loss was 27.9%. Hearing loss was not associated with overall physical activity level (OR, 1.14; 95% CI, 0.90; 1.39) or with domain-specific energy expenditure at work (RR, 0.90; 95% CI, 0.75; 1.08), transport (RR, 1.02; 95% CI, 0.83; 1.25), or leisure (RR, 1.10; 95% CI, 0.86; 1.42). In contrast, hearing loss was associated with high sedentary behavior (OR, 1.81; 95% CI, 1.16; 2.82), with similar estimates after weighting (OR, 1.86; 95% CI, 1.18; 2.94). Subgroup analyses showed no consistent heterogeneity by sex, age, or sleep quality. CONCLUSION: In Chilean adults aged ≥40 years, self-reported hearing loss was associated with prolonged sedentary time but not with overall or domain-specific physical activity. These findings support integrating hearing care with strategies to reduce sedentary behavior.
Challenge-based ex vivo immune profiling reveals stimulus-dependent peripheral immune reprogramming in Alzheimer's disease.
Naranjo-Galvis CA, Zabaleta J, Alliey-Rodriguez N … +1 more , Salamanca-Duque LM
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42351318 · Publisher ↗
Altered immune function is increasingly recognized as a contributor to Alzheimer's disease (AD); however, it remains unclear whether peripheral immune alterations reflect constitutive inflammation or stimulus-dependent c...
Altered immune function is increasingly recognized as a contributor to Alzheimer's disease (AD); however, it remains unclear whether peripheral immune alterations reflect constitutive inflammation or stimulus-dependent changes in immune responsiveness. Addressing this distinction is critical for understanding immune dysregulation in neurodegenerative diseases. In this study, we applied a challenge-based ex vivo immune profiling approach to characterize functional immune responsiveness in patients with AD and in cognitively healthy older adults. Peripheral blood mononuclear cells were exposed to defined innate, antigenic, and mitogenic stimuli, and cytokine and β-amyloid responses were quantified in culture supernatants. Diagnosis-by-stimulus interaction effects were assessed using generalized estimating equation models, adjusted for age and sex. In parallel, exploratory correlation-based immune-amyloid network analyses and hypothesis-driven immunogenetic stratification were performed to investigate biomarker coordination patterns and context-dependent genetic influence. Baseline cytokine concentrations showed limited between-group differences, whereas ex vivo immune challenge revealed selective stimulus-dependent alterations in cytokine production. In contrast, immune stimulation revealed selective amplification of stimulus-evoked responses in AD, particularly involving IFN-γ, IL-4, and IL-10, whereas classical proinflammatory cytokines retained preserved inducibility. Exploratory genotype-stratified analyses suggested potential context-dependent differences in functional immune and β-amyloid responses to immune challenges. Together, these findings indicate that peripheral immune dysregulation in AD is characterized by stimulus-dependent differences in cytokine production that become apparent under immune challenge conditions, highlighting the value of ex vivo immune stimulation assays in translational immunology in neurodegenerative diseases.
Introduction to the special issue on the impact of climate change and air quality on human aging.
Austad SN, Cong Z
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42345254 · Publisher ↗
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State Racism Index and physical function: The REasons for Geographic and Racial Differences in Stroke (REGARDS) study.
Quezada-Pinedo HG, Brown T, Enogela EM … +8 more , Levitan EB, Akinyelure OP, Smith VA, Pinheiro LC, Safford MM, Reid RJ, Akinyemiju TF, Bowling CB
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42340683 · Full text
BACKGROUND: Structural racism contributes to health inequities in the United States. This study aimed to quantify the association between state racism index (SRI) and physical function. METHODS: In a national United Stat...
BACKGROUND: Structural racism contributes to health inequities in the United States. This study aimed to quantify the association between state racism index (SRI) and physical function. METHODS: In a national United States community-based cohort study, 13 661 non-Hispanic Black and White adults who had baseline information (2003-2007), SRI data (2006-2010) and physical function data (2013-2016) were included. Physical function measurements included activities of daily living (ADL), instrumental activities of daily living (IADL), timed walk, and chair stand test. Multivariable generalized regression models (GLMs) and linear regression models were used to evaluate the association between SRI and physical function. Interactions with age, sex, and region were evaluated. RESULTS: Among Black participants, each unit increase in SRI was significantly associated with 2% higher IADL scores (ratio of means [95% confidence interval, CI]: 1.018 [1.007, 1.029]) indicating worse function. This association attenuated after adjustment for socioeconomic factors but was stronger in the United States Stroke Belt region (p for interaction < .05). Among White participants, higher SRI was significantly associated with 2% ADL and 1% IADL lower scores (ratio of means [95% CI]: 0.983 (0.969, 0.997) and 0.985 (0.977, 0.994), respectively) indicating better function. This association was independent of socioeconomic and health-related factors. We did not observe an association between SRI and timed walk or chair stands overall or by race. CONCLUSION: Higher state-level structural racism was associated with worse physical function among Black participants and better physical function for White participants. Associations were influenced by socioeconomic factors and magnified in southern United States.
Older Adults and Extreme Weather Events: Recommendations from the Research Centers Collaborative Network Workshop.
Choi EY, Chu L, Holland AB … +6 more , Balachandran A, Zapico SC, Milani SA, Wong R, Brinkley TE, Kritchevsky SB
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42334962 · Publisher ↗
Extreme weather events are increasingly recognized as critical determinants of health and well-being in later life. To identify priorities for advancing research at the intersection of these events and aging, the Researc...
Extreme weather events are increasingly recognized as critical determinants of health and well-being in later life. To identify priorities for advancing research at the intersection of these events and aging, the Research Centers Collaborative Network convened a 1.5-day interdisciplinary workshop. This article synthesizes discussions across three domains: the effects of weather-related hazards on aging and health outcomes; vulnerabilities and resilience of older adults; and interventions to mitigate risk. Key priorities include longitudinal studies capturing cumulative exposures and long-term outcomes across the life course, greater attention to heterogeneity within older populations, and designing interventions responsive to social and environmental contexts.
Personalizing cancer care for older adults.
Ji J, Sedrak MS
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42329168 · Full text
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Cell-based screen identifies translation state modulators that extend lifespan in D. melanogaster and C. elegans.
Wu B, Wang LJ, Godbole AA … +11 more , Han JH, Keebaugh ES, Chavez G, Sedore CA, Coleman-Hulbert AL, Johnson E, Phillips PC, Lithgow GJ, Driscoll M, Gill MS, Ja WW
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42320027 · Publisher ↗
Aging is associated with declining mitochondrial function and translational regulation-processes modulated by interventions such as dietary restriction (DR) and cold-induced longevity (CHIL). Both DR and CHIL inhibit glo...
Aging is associated with declining mitochondrial function and translational regulation-processes modulated by interventions such as dietary restriction (DR) and cold-induced longevity (CHIL). Both DR and CHIL inhibit global protein synthesis but selectively enhance translation of proteins that support mitochondrial efficiency, stress resistance, and lifespan extension. These translational shifts are mediated, at least in part, by the 4E-BP/eIF4E pathway, which regulates translation according to mRNA 5'-untranslated region (5'-UTR) length and structure. To identify compounds that mimic the beneficial effects of DR/CHIL, we developed a cell-based phenotypic screen that reports on mRNA translation as a function of 5'-UTR length. A pilot screen identified compounds that preferentially increased the expression of mRNAs with short 5'-UTRs relative to those with long 5'-UTRs, and these hits were enriched for known lifespan-extending agents, such as curcumin and rapamycin. Among the novel candidates, fluspirilene significantly extended life in both Drosophila melanogaster and Caenorhabditis elegans, and mitigated age-related locomotor decline in female flies. Fluspirilene-mediated longevity in C. elegans required the DAF-16/FOXO and HLH-30/TFEB transcription factors and the autophagy gene, atg-18. Fluspirilene failed to extend lifespan in two other Caenorhabditis species, as well as in flies maintained on a high-yeast diet, indicating that its pro-longevity effects are constrained by evolutionary divergence and nutrient status. Together, our findings identify fluspirilene as a novel modulator of translation that extends life and preserves healthspan via an autophagy-dependent mechanism and support the promise of drug discovery efforts that modulate translation state as a therapeutic strategy for healthy aging.
Timing Matters: Denture Use for Cognitive Protection is Most Effective Before Major Tooth Loss.
Zhang R, Liu X
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42319901 · Publisher ↗
BACKGROUND: Tooth loss is a potential risk factor for cognitive decline, but the longitudinal evidence on the protective role of dentures and the intervention timing remains limited. This study aimed to investigate the a...
BACKGROUND: Tooth loss is a potential risk factor for cognitive decline, but the longitudinal evidence on the protective role of dentures and the intervention timing remains limited. This study aimed to investigate the associations of tooth loss, denture use, and their changes with distinct cognitive trajectories among older adults. METHODS: We conducted a prospective cohort study of 2,188 community-dwelling older adults from the Chinese Longitudinal Healthy Longevity Survey (2008-2014). Group-based trajectory modeling (GBTM) identified heterogeneous cognitive pathways. Multinomial logistic regression was used to estimate risk ratios (RRs) for the associations of baseline tooth number, denture use, and longitudinal tooth loss with cognitive trajectory membership. RESULTS: GBTM identified two cognitive trajectories: maintained-high (57.4%) and low-declining (42.6%). Baseline tooth loss (0-4 vs. ≥21 teeth: RR = 1.20, 95% CI : 1.02-1.41) and progression to having 0-4 teeth (RR = 1.76, 95% CI : 1.55-2.00) significantly increased the risk of the low-declining trajectory. Denture use was associated with a 13% lower risk (RR = 0.87, 95% CI : 0.78-0.96). Critically, a gradient effect was observed: the protective association was strongest in participants with ≥21 teeth (RR = 0.27, 95% CI : 0.08-0.86, corresponding to a 73% risk reduction) but attenuated with greater tooth loss. CONCLUSIONS: Tooth loss is a significant risk factor for adverse cognitive trajectories, while denture use is associated with a mitigated risk. The effectiveness of dentures is highly dependent on timing, with the greatest cognitive benefit achieved when used early, before major tooth loss occurs. These findings underscore the importance of timely prosthodontic intervention as a potential strategy for cognitive preservation in older adults.
Treatment completion rate, toxicity, and 90-Day unplanned readmission in older adults with esophageal squamous cell carcinoma receiving radiotherapy alone versus concurrent chemoradiotherapy.
Xie J, Zhang L, Yuan Y … +4 more , Yan X, Wang Y, Li S, Yu X
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42308557 · Publisher ↗
BACKGROUND: 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 chemoradiothe...
BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
The relationship between muscle fatty infiltration and musculoskeletal health: an imaging-based population study.
Chen X, Bai H, Ding Z … +5 more , Tan J, Cai L, Liu C, Chen J, Sun Y
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42302723 · Publisher ↗
BACKGROUND: Muscle fatty infiltration (MFI) is a hallmark of skeletal muscle degeneration, yet its independent associations with musculoskeletal disorders remain debated. METHODS: Using data from the UK Biobank (2014-202...
BACKGROUND: Muscle fatty infiltration (MFI) is a hallmark of skeletal muscle degeneration, yet its independent associations with musculoskeletal disorders remain debated. METHODS: Using data from the UK Biobank (2014-2023), we analyzed associations of MFI (Dixon magnetic resonance imaging) with skeletal muscle (sarcopenia, grip strength [kg], appendicular lean mass index [ALMI, kg m-2]); joints (total/knee/hip osteoarthritis [HOA]); bone (bone mineral density [BMD, g cm-2], heel BMD, osteoporosis [OP], fractures); and physical performance (self-reported usual walking pace, incident falls). Multivariable regression with false discovery rate (FDR) correction was applied. RESULTS: A total of 12 801 participants were included (mean age 67.23 ± 7.44 years; 52.01% female). Each 1% higher MFI was associated with lower hand grip strength (β = -0.58 kg; 95% confidence interval [CI] -0.66 to -0.49) and ALMI (β = -0.13 kg m-2; 95% CI, -0.13 to -0.12), higher odds of sarcopenia (OR = 1.50; 95% CI, 1.37-1.63), total osteoarthritis (OA, OR = 1.12; 95% CI, 1.09-1.16), knee OA (OR = 1.20; 95% CI, 1.15-1.25), HOA (OR = 1.10; 95% CI, 1.02-1.17), falls (OR = 1.08; 95% CI, 1.03-1.13), and slower walking pace (OR = 0.84; 95% CI, 0.82-0.86). Associations with OP and fractures were attenuated to non-significance after adjustment for age, sex, ethnicity, body mass index (BMI), physical activity, socioeconomic deprivation, education, smoking, alcohol intake, and chronic diseases. Interaction analyses revealed that associations were most pronounced among lean (BMI <25 kg m-2), younger (<65 years), and metabolically uncomplicated individuals. CONCLUSIONS: Muscle fatty infiltration is adversely associated with muscle health, joint degeneration, and physical performance, while its independent contribution to bone health remains equivocal. The strength of its association with musculoskeletal outcomes is context-dependent, being most pronounced in lean, younger, and metabolically uncomplicated individuals.
An appropriate ASMI cutoff value enhances utilization of the CHARLS database for studying sarcopenia.
An L, Gao W, Ren L … +2 more , Wang J, Wang Y
J Gerontol A Biol Sci Med Sci · 2026 Jul · PMID 42289984 · Publisher ↗
BACKGROUND: Sarcopenia research based on the China Health and Retirement Longitudinal Study (CHARLS) frequently employs an anthropometric equation to estimate appendicular skeletal muscle mass (ASM). Liu et al. recently...
BACKGROUND: Sarcopenia research based on the China Health and Retirement Longitudinal Study (CHARLS) frequently employs an anthropometric equation to estimate appendicular skeletal muscle mass (ASM). Liu et al. recently questioned the reliability of this equation. We aimed to validate the equation against bioelectrical impedance analysis (BIA) measurements and to examine the impact of different cutoff values for low muscle mass used in CHARLS-based studies. METHODS: We retrospectively analyzed BIA data from 548 diabetic patients (age range 23-90 years, median 62 years; 41.06% women). ASM measured by BIA (bASM) was compared with ASM calculated by the equation (cASM). Spearman correlation, intraclass correlation coefficient (ICC), and Bland‑Altman analysis were performed. Two commonly used height‑adjusted ASM (ASM/Ht2) cutoff sets were tested against the AWGS 2019 reference standard. RESULTS: cASM correlated strongly with bASM (r = 0.94, p < .001). ICC demonstrated excellent agreement (0.933; 95% CI 0.919-0.945). Bland‑Altman plots showed acceptable limits of agreement. One cutoff set (men 7.05, women 5.63 kg/m2) showed almost perfect agreement with AWGS 2019 (Kappa = 0.909, McNemar p = 1.000), whereas the other set (men 6.79, women 4.90 kg/m2) showed only moderate agreement (Kappa = 0.492) and a significant level of discordance (McNemar p < .001). CONCLUSION: The ASM estimation equation remains valid for CHARLS-based sarcopenia research, including in diabetic populations. To avoid misclassification and ensure cross-study comparability, we recommend using AWGS 2019-aligned cutoffs.
High Frailty Index Scores Predict Mortality and Changes in Blood-Based Biomarkers in Aging Female Mice.
Bisset ES, Gujar S, Rockwood K … +1 more , Howlett SE
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42275167 · Publisher ↗
Variability in aging rates can be quantified with a frailty index (FI) based on the accumulation of clinically evident health deficits in aging mice. Deficit accumulation characteristics have been investigated in longitu...
Variability in aging rates can be quantified with a frailty index (FI) based on the accumulation of clinically evident health deficits in aging mice. Deficit accumulation characteristics have been investigated in longitudinal studies of male but not female mice. We investigated frailty longitudinally in aging female C57BL/6N mice (n = 79; 6-29 months) and determined whether high frailty scores predicted mortality and abnormalities in blood-based biomarkers. Female mice exhibited a gradual rate of deficit accumulation (slope=0.025) as previously observed in males. High FI scores (>0.20 at 18 months) predicted mortality during follow-up at 24 months and older (p = 0.015). The range of FI scores broadened with age, with a submaximal limit to frailty of 0.55, similar to values in males. Few correlations were significant between blood-based biomarkers and chronological age in female mice, with only urea (r = 0.39; p = 0.006) and creatinine (r = 0.35; p = 0.01) levels exhibiting positive correlations with age. By contrast, many biomarkers were closely graded by the degree of frailty in females. Urea (r = 0.46, p = 0.001), creatinine (r = 0.35; p = 0.01) and chloride (r = 0.49; p = 0.001) were all positively associated with FI scores whereas glucose (r=-0.63; p = 0.001), hematocrit (r=-0.53; p = 0.001) and hemoglobin (r=-0.45; p = 0.002) were negatively correlated. Interestingly, in a small cohort of aging male mice (n = 15; aged 13-27 months), no biomarkers significantly correlated with age, despite many being correlated with frailty. Characteristic features of deficit accumulation are present in female mice. High FI scores based on the accumulation of clinically evident health deficits forecast early mortality and predict abnormalities in blood-based biomarkers better than chronological age.
Leisure-time physical activity and metabolomic trajectories over the transition from late midlife to old age.
Ruutu K, Verbeeren J, Mikkola TM … +3 more , Laine MK, Eriksson JG, Wasenius NS
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42275166 · Publisher ↗
Physical activity may counteract aging-associated disruptions in the metabolome. We investigated how leisure-time physical activity (LTPA) associates with the metabolome in late midlife and with 15-year metabolomic traje...
Physical activity may counteract aging-associated disruptions in the metabolome. We investigated how leisure-time physical activity (LTPA) associates with the metabolome in late midlife and with 15-year metabolomic trajectories. The study included 1816 Helsinki Birth Cohort Study participants at baseline (mean age 61.6 years), with 985, 996, and 740 participants at the 5-, 10-, and 15-year follow-ups, respectively. LTPA was assessed at baseline and after 15 years using a validated questionnaire and expressed as METhours/week. Nuclear magnetic resonance-based metabolomics data from fasting blood samples were used to analyze 161 biomarkers at baseline and at each follow-up. Weighted Gene Co-Expression Network Analysis was performed on the metabolomics data to identify 11 metabolomic biomarker modules. Baseline associations were analyzed using restricted cubic splines and longitudinal associations with linear mixed-effects models. Analyses were sex-stratified, covariate-adjusted, and corrected for multiple testing. At baseline, LTPA was nonlinearly associated with albumin in women and with nine biomarkers in men in the crude, but not fully adjusted, model. Over the follow-up, baseline LTPA was associated with the age-related trajectory of triglyceride-enriched high-density lipoprotein (HDL) module in men (age x LTPA interaction p = 0.041). In the high LTPA group, the trajectory declined significantly compared to the low (p = 0.004) and moderate LTPA groups (p = 0.045). No associations were found in women. To conclude, in men, higher LTPA in late midlife predicted a favorable 15-year trajectory of triglyceride-enriched HDL. Our findings indicate that an active lifestyle is associated with more favorable metabolomic trajectories related to cardiometabolic health across late midlife and old age.
Validating ICD code case definitions for condition case ascertainment in multimorbidity measurement: a retrospective chart review.
Kang AJ, Tseng CH, Wei MY
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42274218 · Publisher ↗
BACKGROUND: Accurate case ascertainment of chronic conditions is critical for research, clinical decision-making, and population health management, especially for older adults with high multimorbidity. However, validatio...
BACKGROUND: Accurate case ascertainment of chronic conditions is critical for research, clinical decision-making, and population health management, especially for older adults with high multimorbidity. However, validation of ICD-based case definitions in the electronic health record (EHR) data remains limited. We sought to determine whether a single ICD code is sufficient for accurate identification of chronic conditions in the EHR, or whether multiple codes improve validity. METHODS: Population-based retrospective chart review, 2013-2019, at large academic tertiary and quaternary care health system. Our sample included adults aged ≥18 years with ≥2 encounters within a 2-year period. We conducted gold-standard chart review to determine validity of using ≥1 or ≥ 2 ICD codes to identify 23 chronic conditions included in the validated multimorbidity-weighted index, specifically those lacking robust case definitions in EHR data. Validation statistics included positive predictive value (PPV), negative predictive value (NPV), Cohen's kappa, sensitivity, specificity, and percent sample size loss associated with stricter ≥2 ICD code case definitions. RESULTS: The final analytic sample included 780,873 adults (mean (SD) age 47.7 (18.0) years, 56.9% female). For 22 of 23 conditions, use of ≥ 1 ICD code yielded a PPV ≥0.70. Requiring ≥2 ICD codes yielded minimal improvement in PPV but with substantial sample size loss that ranged from 16.8% to 64.5%. CONCLUSIONS: ≥1 ICD code was sufficient to accurately identify most chronic conditions with high accuracy in the EHR over a multi-year timeframe. However, condition-specific validation remains essential, as performance varies by condition.
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