{"title":"Sex matters: the effect of physical activity on brain perfusion.","authors":"Brittany Intzandt,Safa Sanami,Julia Huck,Louis Bherer,Claudine J Gauthier","doi":"10.1093/gerona/glaf154","DOIUrl":"https://doi.org/10.1093/gerona/glaf154","url":null,"abstract":"Cerebral blood flow (CBF) declines consistently in aging and this decline is a critical component of several late life diseases. Understanding why this occurs in normal aging, prior to pathological changes, is crucial. Physical activity (PA) is a powerful preventative tool to improve vascular health and preserves CBF in both sexes, though females may benefit most throughout the lifespan. There is currently limited knowledge however about what intensity is needed to derive benefit, and if there are sex differences in this relationship with intensity. Here, CBF and PA were investigated according to sex and age. A total of 573 participants aged 36 to 90 years were included from the Human Connectome Lifespan Aging. Linear and quadratic regressions were utilized to investigate relationships among CBF and PA intensities in each of the four groups. Vigorous PA in middle aged males was related to greater CBF (p < 0.05). Older females showed benefit at all intensities (p < 0.05). Middle aged females were least sensitive to the effects of PA. In all groups except older males, hippocampal CBF was only dependent on vigorous PA (p < 0.05). These results highlight the sex-specific relationship between CBF and PA, and the importance of tailoring recommendations to sex and lifespan stage including addressing and updating current public health guidelines to maximize adoption and benefit, specific to brain health.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652935","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}
Matthew E Growdon,Bocheng Jing,W James Deardorff,Earl J Morris,W John Boscardin,Leah J Blank,Tasce Bongiovanni,Kenneth S Boockvar,Michael A Steinman
{"title":"Loop diuretics and subsequent use of urinary symptom medications in older adults: evaluation of a possible prescribing cascade.","authors":"Matthew E Growdon,Bocheng Jing,W James Deardorff,Earl J Morris,W John Boscardin,Leah J Blank,Tasce Bongiovanni,Kenneth S Boockvar,Michael A Steinman","doi":"10.1093/gerona/glaf150","DOIUrl":"https://doi.org/10.1093/gerona/glaf150","url":null,"abstract":"BACKGROUNDLoop diuretic (LD) use may lead to a prescribing cascade whereby urinary symptoms are ascribed to genitourinary syndromes and treated with urinary symptom medications (USMs). We investigated if LDs lead to increased USM use among older adults and whether this potential prescribing cascade varies across key characteristics.METHODSThis was a prescription sequence symmetry analysis of Veterans Administration data, involving veterans ≥66 years who initiated treatment with LD (2010-2019). USMs were antimuscarinics, beta-3 adrenergic agonists, peripheral alpha-1 blockers, and 5-alpha reductase inhibitors. We calculated the adjusted sequence ratio (aSR), assessing the cascade signal while adjusting for secular trends, and stratified by key variables.RESULTSThere were 17,735 veterans who initiated USM within 6 months after LD and 25,190 who initiated USM within 6 months before LD; 99% were male. Unexpectedly, the aSR was 0.74 (95% CI, 0.73-0.76), meaning patients were 26% less likely to initiate USM within 6 months after initiating LD vs 6 months before. This inverse relationship held in men (aSR, 0.74, 95% CI, 0.72-0.76) but was null in women (aSR, 1.00, 95% CI, 0.80-1.26). In men without baseline urinary symptoms, we observed the LD-USM cascade in patients with heart failure (aSR 1.52, 95% CI, 1.41-1.63) and multimorbidity (e.g., Charlson 4th quartile, aSR 1.24, 95% CI, 1.10-1.39).CONCLUSIONSWe did not find evidence for a LD-USM cascade among predominantly male older adults overall. Clinicians may under-prescribe USMs in patients receiving LDs, perhaps due to strong attribution of urinary symptoms to LD use.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"104 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640176","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}
Frederick Sieber,Mallak K Alzahrani,Qian-Li Xue,Ravi Varadhan,Thomas Laskow,Charles Brown,Brian Buta,Julius Oni,Fangyu Liu,Jeremy Walston,Karen Bandeen-Roche
{"title":"A Taxonomy to Characterize Stressor Variation in Studies of Physical Resilience and its Illustration in Total Knee Replacement.","authors":"Frederick Sieber,Mallak K Alzahrani,Qian-Li Xue,Ravi Varadhan,Thomas Laskow,Charles Brown,Brian Buta,Julius Oni,Fangyu Liu,Jeremy Walston,Karen Bandeen-Roche","doi":"10.1093/gerona/glaf151","DOIUrl":"https://doi.org/10.1093/gerona/glaf151","url":null,"abstract":"BACKGROUNDThis study aimed to develop a conceptual framework and empirical measures to characterize stressor magnitude and type in the context of total knee replacement (TKR) and to investigate their relationship with resilience phenotypes.METHODSA sequential elicitation process was used to identify key stressor characteristics, categorized as exogenous or endogenous. Resilience phenotypes were created as (post-surgery - (baseline, or pre-surgery)) changes in four measures of physical function/symptoms selected based on their relevance to TKR outcomes. These measures included: the Short Physical Performance Battery score (SPPB), the Pittsburgh fatigability scale (PFS), the Short Form-36 (SF-36) physical component summary score, and the knee injury and osteoarthritis outcome score (KOOS) quality of life subscale.RESULTSAnalyses revealed few associations between baseline phenotype measurements and stressor characteristics. Several consistent adjusted associations were observed between stressor characteristics and six-month resilience phenotypes. All endogenous measurements analyzed exhibited the expected direction of association with PFS change from baseline to 6 months, indicating higher stress levels predicted a diminished return of vigor post-surgery; intraoperative blood loss exhibited the strongest association. Outpatient vs inpatient procedures were associated with more beneficial change from baseline to 6 months of all resiliency phenotypes; SPPB score recovery exhibited the strongest association. Other individual strong associations were observed, but with less consistency across phenotypic trajectories or stressor characteristics.CONCLUSIONSThe study highlights the importance of considering stressor variation in resilience research. The conceptual framework and empirical measures developed provide a foundation for future investigations into the factors influencing resilience to physical stressors in older adults.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639955","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":"Time to mobilization in hours after surgery for hip fracture and 30-day mortality-A study on 36,229 patients from the Danish Hip Fracture Registry.","authors":"Morten Tange Kristensen,Ina Trolle Andersen,Bjarke Viberg,Alma Becic Pedersen","doi":"10.1093/gerona/glaf147","DOIUrl":"https://doi.org/10.1093/gerona/glaf147","url":null,"abstract":"BACKGROUNDEarly mobilization after hip fracture (HF) is a key indicator in national registries and associated with reduced mortality, but in-depth analysis of time in hours for mobilization is lacking. We described the clinical profile and 30-day mortality by time-intervals in hours for mobilization after HF surgery.METHODSUsing Danish registries, we included HF patients aged ≥65 years (from year 2016-2021). Exposure-time in hours from start of surgery to mobilization. Outcome-mortality within 2-30 days of surgery. Primary mortality analysis-we compared mobilizations >24-36h versus ≤24h by calculating weighted risks, risk differences (RD) and hazard ratios (HR) using inverse probability of treatment weighted method. Secondary mortality analyses-we compared mobilizations >24-36h and >12-24h versus ≤12h.RESULTSWe included 36,229 patients (67.3% women) with a median age of 82.6 years. Patients mobilized ≤24h had similar age, BMI, and marital status, but were slightly more living in own residence, have high pre-fracture mobility, high education, and less comorbidity than patients mobilized >24-36h. The weighted risk of 30-day mortality for mobilization >24-36h versus ≤24h was 10.43% and 7.89% with corresponding RD and HR of 1.67 (0.54,2.80) and 1.22 (1.07,1.38). The weighted RD and HR were 1.62% (0.89, 2.35) and 1.25 (1.12,1.39) for >12-24 versus ≤12h, and 1.33% (0.17-2.49) and 1.16 (1.02,1.31) for >12-24h versus >24-36h.CONCLUSIONThe 30-day mortality increases with the increasing time to mobilization after HF surgery. We suggest focusing on time in hours to mobilization with a 24-hour or even earlier timepoint after surgery.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622173","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}
Xin Wen Ong, David G Le Couteur, Louise M Waite, Janani Thillainadesan
{"title":"End-of-Life Care in Hospitalized Patients with Dementia","authors":"Xin Wen Ong, David G Le Couteur, Louise M Waite, Janani Thillainadesan","doi":"10.1093/gerona/glaf120","DOIUrl":"https://doi.org/10.1093/gerona/glaf120","url":null,"abstract":"Background As the aging population grows, the care provided to patients with dementia at the end of life represents a critical area of geriatric and palliative care. This study aimed to describe the care provided to hospitalized patients with dementia who died during their hospital stay. Methods A retrospective cohort study was conducted at a teaching hospital in Sydney, Australia. The study included patients with dementia who died during hospitalization. Data were collected on demographic characteristics, clinical management, and documentation of key care processes, including advance care planning, resuscitation orders, and discussions about oral nutrition and hydration. Results The study cohort comprised patients with a mean age of 87.2 ± 7.2 years (n = 100), 63% of whom had lived in nursing homes. Geriatric medicine teams cared for a large proportion of patients (63%), and their patients were more likely to be older, from a nursing home, and to die from pneumonia compared to those admitted in palliative care teams. Recommended care processes were implemented in the majority of patients with advance care planning and resuscitation orders being the most frequently documented, and discussions about oral nutrition and hydration the least frequent. Conclusion This study highlights the integral role of geriatrics services in providing end-of-life care for hospitalized patients with dementia, and underscore opportunities to enhance the quality and consistency of care for this population.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144612842","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}
Leah Moubadder, Junyu Chen, Elizabeth S Clausing, Katrina L Kezios, Karen N Conneely, Pam Factor-Litvak, Diddier Prada, Andrea Baccarelli, Rachel C Shelton, Bruce G Link, Shakira F Suglia
{"title":"Impact of Socioeconomic Conditions Across the Life Course on Epigenetic Age Acceleration: Evidence from a Longitudinal Cohort","authors":"Leah Moubadder, Junyu Chen, Elizabeth S Clausing, Katrina L Kezios, Karen N Conneely, Pam Factor-Litvak, Diddier Prada, Andrea Baccarelli, Rachel C Shelton, Bruce G Link, Shakira F Suglia","doi":"10.1093/gerona/glaf139","DOIUrl":"https://doi.org/10.1093/gerona/glaf139","url":null,"abstract":"Background We investigated whether adulthood socioeconomic status (SES) mediates the association between childhood SES and biological aging in a longitudinal cohort (N = 359). Methods SES was measured using composite scores from prospective measures in childhood and at age 50. Peripheral blood DNA methylation (DNAm) was measured at approximately 50 years of age. DNAm age acceleration (AA) was quantified for DNAm “clocks” (Horvath, Hannum, PhenoAge, GrimAge) and a DNAm pace-of-aging measure (DunedinPACE). Linear regression was used to evaluate the associations between SES at each life stage and DNAm AA. Adulthood SES was evaluated as a mediator between childhood SES and DNAm AA using marginal structural models. Results Compared to high childhood SES, low childhood SES was associated with AA for GrimAge (β=0.99, 95% confidence interval [CI]: 0.08, 1.91) and DunedinPACE (β=0.05, 95% CI: 0.02, 0.08). Low adulthood SES, compared to high adulthood SES, was also associated with AA for GrimAge (β=2.31, 95% CI: 1.35, 3.28) and DunedinPACE (β=0.05, 95% CI: 0.02, 0.08). The association between childhood SES and both clocks were partially mediated by adulthood SES. No other clocks were associated with SES. Conclusion Early and late-life socioeconomic conditions accelerate biological aging. Larger studies exploring mediators and interventions are needed for equitable aging mitigation.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"106 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144611192","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}
Jacinta Correia, Promit Sinha Roy, Kaitlyn G Holden, Marian L Kohut, Hua Bai
{"title":"Aging impairs peroxisome biogenesis in human B cells","authors":"Jacinta Correia, Promit Sinha Roy, Kaitlyn G Holden, Marian L Kohut, Hua Bai","doi":"10.1093/gerona/glaf148","DOIUrl":"https://doi.org/10.1093/gerona/glaf148","url":null,"abstract":"Emerging evidence highlights the critical role of cellular metabolism in immune cell activation, development, and function. Peroxisomes, key metabolic organelles, maintain metabolic homeostasis, yet their role in immune cells remains underexplored. While animal studies show age-related declines in peroxisome biogenesis, this process is unconfirmed in human aging. We investigated peroxisome biogenesis in human peripheral blood mononuclear cells (PBMCs) and found a significant decline in aged CD19+ B cells compared to CD4+ T cells, CD8+ T cells, and CD14+ monocytes. B cell aging also reduces peroxisomal matrix enzyme import, evidenced by decreased SKL-containing enzymes and mature ACOX1, alongside downregulation of PEX19 and E3 ubiquitin ligases PEX2, PEX10, and PEX12. These findings confirm an evolutionarily conserved and age-related decline in peroxisome biogenesis. Further, our work unveils cell type-specific changes in aging human PBMCs, and provides new insights into peroxisome-mediated immunometabolism and B cell aging.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593909","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}
Yumeng Lin, Mengjun Yan, Lili Shen, Yi Wang, Haibei He, Zhongyu Han, Haoran Chen, Aijun Liu
{"title":"Therapeutic Approaches to Delay Lung Aging: Understanding Cellular and Immune System Changes in the Older Adults","authors":"Yumeng Lin, Mengjun Yan, Lili Shen, Yi Wang, Haibei He, Zhongyu Han, Haoran Chen, Aijun Liu","doi":"10.1093/gerona/glaf149","DOIUrl":"https://doi.org/10.1093/gerona/glaf149","url":null,"abstract":"As human lifespan extends, the impact of aging on health has become a significant research area, with increasing focus on pulmonary health. The lung, as a complex organ, undergoes various microenvironmental changes during aging, which are crucial for lung function and the development of related diseases. Aging affects the pulmonary microenvironment in multiple ways, accelerating the decline in lung function. One of the key mechanisms of aging is cellular senescence, which refers to the state in which cells lose their ability to divide and function properly. Cellular senescence leads to a decline in the regenerative capacity of lung cells and may trigger inflammatory responses. Correspondingly, aging also affects the immune system, making the older adults more susceptible to respiratory infections. Moreover, intercellular communication within the pulmonary microenvironment changes during aging, potentially compromising lung structural integrity and function. Understanding these processes is essential for developing new therapeutic strategies to delay lung aging and improve pulmonary health in the older adults. This review focuses on the impact of aging on the pulmonary microenvironment, including changes in cellular senescence, alterations in immune responses, and the involved molecular mechanisms, aiming to provide insights for the diagnosis and treatment of age-related pulmonary diseases.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593911","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}
Zoe H Smith,Liam F Fitzgerald,Rajakumar Nagarajan,Kate L Hayes,Martin Meyerspeer,Alfredo L Lopez Kolkovsky,Jane A Kent
{"title":"Does Lower Oxidative Capacity Influence the Relative Contributions of ATP-Producing Pathways During Muscular Work in Aging?","authors":"Zoe H Smith,Liam F Fitzgerald,Rajakumar Nagarajan,Kate L Hayes,Martin Meyerspeer,Alfredo L Lopez Kolkovsky,Jane A Kent","doi":"10.1093/gerona/glaf142","DOIUrl":"https://doi.org/10.1093/gerona/glaf142","url":null,"abstract":"Although the capacity of skeletal muscle to produce ATP via oxidative phosphorylation may decrease in some muscles in older age, the influence of a lower capacity on relative use of oxidative and non-oxidative ATP production pathways in vivo during contractions is unclear. To test the hypothesis that lower oxidative capacity would yield greater non-oxidative ATP production, 19 young (10F) and 17 older (9F) adults performed knee extensor muscle contractions in a 3-tesla magnetic resonance system. Phosphorus metabolites were used to calculate oxidative capacity (rate constant of phosphocreatine recovery; k PCr, s-1) and estimate the maximal rate of oxidative ATP production (Vmax, mM·s-1) following a 24-s dynamic contraction protocol. Next, ATP production (mM·s-1) by the creatine kinase reaction (ATPCK), glycolysis (ATPGLY), and oxidative phosphorylation (ATPOX) was determined during 4 min of dynamic muscle contractions. Proton spectroscopy of deoxymyoglobin was also acquired in a subset (n = 12) and used to calculate the cytosolic partial pressure of oxygen (PO2). Young muscle had a greater k PCr (0.023±0.005s-1, mean±SD) than older muscle (0.020±0.003s-1, p = 0.033). ATPCK, ATPGLY, and ATPOX were not different by group (p ≥ 0.129), but ATPOX as %Vmax was lower in younger than older muscle (55±14%, 71±10%, respectively, p < 0.001). Intracellular oxygen availability (PO2) was not different by group (young: 2.4±0.7 Torr, n = 7; older: 3.2±1.6 Torr, n = 5, p = 0.371). These new findings suggest a bioenergetic rigidity in older muscle, such that it adapts to the energetic demand by using oxidative ATP production at a greater percentage of capacity rather than switching to an increased use of non-oxidative ATP production.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533300","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}
C Barrett Bowling,Richard Sloane,Richard A Faldowski,Carl Pieper,Tyson Brown,Erin E Dooley,Brett T Burrows,Ankeet S Bhatt,Donald M Lloyd-Jones,Cora E Lewis,Kelley Pettee Gabriel
{"title":"Association of multimorbidity trajectories from early adulthood through middle age with middle-age physical function.","authors":"C Barrett Bowling,Richard Sloane,Richard A Faldowski,Carl Pieper,Tyson Brown,Erin E Dooley,Brett T Burrows,Ankeet S Bhatt,Donald M Lloyd-Jones,Cora E Lewis,Kelley Pettee Gabriel","doi":"10.1093/gerona/glaf140","DOIUrl":"https://doi.org/10.1093/gerona/glaf140","url":null,"abstract":"BACKGROUNDChronic conditions can develop early in the adult life course and accumulate at different rates. However, the association between multimorbidity trajectory groups from young adulthood and physical function in midlife has not been well studied.METHODSData are from 2,018 Coronary Artery Risk Development in Young Adults (CARDIA) study participants who completed a PROMIS Function Short Form and five physical performance tests (gait speed, grip strength, balance, chair stands, 6-minute-walk, composite score range 0-20, higher is better). Multimorbidity trajectory groups were previously identified using latent class growth models and characterized by the age of onset and rapidity of accumulation of conditions: (1) early-fifties, slow (E50S), (2) mid-forties, fast (M40F), (3) mid-thirties, fast (M30F), (4) late-twenties, slow (L20F), (5) mid-twenties, slow (M20S), and (6) mid-twenties, fast (M20F). The association of multimorbidity trajectory group with physical function scores in middle age were estimated using multiple linear regression.RESULTSAt the time of physical function measurement, participants had a mean age (SD) of 60.0 (3.6) years, 58.2% were female, and 44.4% were Black. Compared to participants in the E50S class, adjusted mean differences in the PROMIS score were -1.37, -1.44, -3.18, and -2.53 for those in the M40F, M30F, L20F, M20F, respectively (all p-values <0.01). Compared to E50S adjusted mean differences in the composite performance scores were -1.48, -0.44, and -1.51 for L20F, M20S, M20F, respectively (all p-values <0.05).CONCLUSIONSEarlier onset and more rapid accumulation of chronic conditions from early adulthood may identify those at risk for functional limitations in midlife.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"633 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520893","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}