Izco-Cubero M, Lachén-Montes M, Chenhuichen C
… +8 more, Cedeno-Veloz BA, Echeverría-Beistegui I, Zambom-Ferraresi F, Zambom-Ferraresi F, de la Riva MLF, Álvarez-Rodríguez P, Santamaría E, Martínez-Velilla N
J Gerontol A Biol Sci Med Sci
· 2026 Jun · PMID 42063204
·
Full text
Hospitalization in older adults often leads to disability in daily living activities, thereby increasing the risk of functional and cognitive impairments. Thisrandomized controlled trial analyzed the serum protein profil...Hospitalization in older adults often leads to disability in daily living activities, thereby increasing the risk of functional and cognitive impairments. Thisrandomized controlled trial analyzed the serum protein profile of patients admitted to an acute geriatric unit who engaged in supervised multicomponent functional exercise program compared with a control group. Potential protein biomarkers were assessed using the Olink serum proteomics platform employing two predefined panels: Cardiometabolic and Inflammation. Notably, the short-term exercise intervention was associated with moderate but consistent changes in the serum proteome. Nominal differences (p < .05, unadjusted) were observed for amyloid beta precursor-like protein 1 (APLP1), complement C1q tumor necrosis factor-related protein 1 (C1QTNF1), interleukin-8 (CXCL8), interleukin-7 (IL-7), M-phase phosphoprotein 8 (MPHOSPH8), neurotrophin 3 (NTF3), tissue-type plasminogen activator (PLAT), SFRS1-interacting protein (PSIP1), pleiotrophin (PTN), cardiac-type troponin I (TNNI3), and von Willebrand factor (vWF); conversely, levels of CD40 ligand (CD40LG) were reduced. These findings suggest that short-term multicomponent functional exercise during acute hospitalization can induce changes in the serum proteome. These molecular alterations provide exploratory insights into the biological processes associated with the functional benefits observed following the intervention in hospitalized older adults.
Lv Z, Li K, Liu C
… +4 more, Liu P, Kou Z, Zhang M, Gao D
J Gerontol A Biol Sci Med Sci
· 2026 May · PMID 42054588
·
Publisher ↗
BACKGROUND: This study aimed to investigate the associations between phenotypic age acceleration (PhenoAgeAccel) and different CVD outcomes and mortality, examine its relationship with cardiac structure and function usin...BACKGROUND: This study aimed to investigate the associations between phenotypic age acceleration (PhenoAgeAccel) and different CVD outcomes and mortality, examine its relationship with cardiac structure and function using cardiac magnetic resonance imaging (CMR), and explore potential mediating pathways involving cardiac remodeling and cardiometabolic diseases. METHODS: PhenoAgeAccel was defined as the residual of PhenoAge, derived from 9 biomarkers, regressed on chronological age. We included 31 722 UK Biobank participants (mean age 54.6 years; 48.1% male) with complete baseline biomarker and CMR data. Multiple Cox proportional hazards models were used to assess associations with CVD outcomes and mortality. Multivariable linear regression examined associations with CMR-derived cardiac measures, and multiple mediation analyses were performed to evaluate potential mediating roles. RESULTS: Higher PhenoAgeAccel was independently associated with increased risks of any CVD, ischemic heart disease (IHD), heart failure, all-cause mortality, and CVD mortality. Each standard deviation increase in PhenoAgeAccel (4.63 years) was associated with 7%, 9%, 29%, 14%, and 16% higher risks of these outcomes, respectively, but not with arrhythmias or cerebrovascular disease. Associations with any CVD, IHD, and CVD mortality were stronger in women. Higher PhenoAgeAccel was also associated with adverse cardiac remodeling, including lower left ventricular volume, stroke volume, mass, LVGFI, and ejection fraction. Cardiac remodeling and cardiometabolic diseases partially mediated these associations. CONCLUSIONS: Our study examines the association between accelerated aging and cardiac phenotypes and their important independent mediating role in the accelerated aging-cardiovascular outcome relationship. Improving cardiac remodeling and metabolic health may mitigate the effects of biological aging on CVD risk.
J Gerontol A Biol Sci Med Sci
· 2026 May · PMID 42045006
·
Publisher ↗
BACKGROUND: Socioeconomic status (SES) is a key social determinant of diverse health outcomes. This study examined the association of SES with the risk of frailty among adults aged over 45, and further explored the speci...BACKGROUND: Socioeconomic status (SES) is a key social determinant of diverse health outcomes. This study examined the association of SES with the risk of frailty among adults aged over 45, and further explored the specific role of lifestyle. METHODS: A total of 26 978 individuals from three nationwide cohorts were included in the analysis, with 57.57% of them aged 60 years and older. Frailty was evaluated using the frailty index (FI) constructed from 40 health-related items, and frailty trajectories were identified using group-based trajectory modeling. Latent class analysis (LCA) was conducted to determine the optimal SES pattern based on occupation, education, and income. The lifestyle score comprised smoking, drinking, exercise, sleep, social participation, and body shape. Cox and Logistic regression models, mediation and joint analysis, and multiple sensitivity analysis were used. RESULTS: Over a median follow-up of 7.49 years, 7636 participants developed frailty. Low SES was a risk factor for frailty (HR = 1.51, 95% CI, 1.43-1.60) and high-ascending frailty trajectory (OR = 1.73, 95% CI, 1.60-1.87). Lifestyle mediated 8.82% of the association for SES and frailty, 8.37% of the association for SES and high-ascending frailty trajectory. Participants exhibiting both low SES and unhealthy lifestyle demonstrated the highest risk of frailty (HR = 2.13, 95% CI, 1.94-2.34) and high-ascending frailty trajectory (OR = 2.55, 95% CI, 2.23-2.92). CONCLUSIONS: Unhealthy lifestyle partially mediated the association of low SES with frailty in adults aged over 45. Therefore, simultaneous interventions tailored to socioeconomic and lifestyle factors are needed to prevent frailty.
J Gerontol A Biol Sci Med Sci
· 2026 May · PMID 42045005
·
Full text
BACKGROUND: Arterial stiffness, a predictor of cardiovascular disease, reflects both structural properties of the arterial wall and load-dependent effects of intra-arterial pressure. Although exercise improves vascular h...BACKGROUND: Arterial stiffness, a predictor of cardiovascular disease, reflects both structural properties of the arterial wall and load-dependent effects of intra-arterial pressure. Although exercise improves vascular health, its optimal intensity and effects on these stiffness components remain unclear in older adults. METHODS: We analyzed 34 105 UK Biobank participants (mean age 64; 49% female) with finger-derived arterial stiffness index (ASI) and International Physical Activity Questionnaire-assessed activity. ASI was regressed on mean arterial pressure and decomposed into pressure-independent (ASI-PI; residuals) and pressure-dependent (ASI-PD; total minus ASI-PI) components. Multivariable models tested associations with total and intensity-specific MET-minutes, adjusting for demographic, socioeconomic, cardiometabolic, and medication factors. RESULTS: Higher overall physical activity was associated with lower total ASI (9.45 ± 2.93 for high activity vs 9.72 ± 2.89 for low; p < .001), and lower ASI-PI (-0.01 ± 2.91 for high vs 0.26 ± 2.88 for low vs; p < .001). The association between physical activity and ASI-PD was minimal. Each 1 SD higher total MET was associated with lower ASI-PI (β = -0.094, 95% CI -0.119 to -0.068; p < .001) but not ASI-PD. In intensity-specific models, vigorous activity was consistently associated with lower ASI-PI (β ≈-0.12; p < .001), whereas moderate activity showed modest positive associations, and walking activity was not significantly related. When total activity volume was held constant, vigorous METs were associated with lower ASI-PI, while associations with ASI-PD remained negligible. CONCLUSIONS: Vigorous activity was consistently associated with lower ASI-PI, suggesting beneficial vascular adaptations to exercise beyond its effects on hemodynamic load.
Hou Y, Zeng Z, He S
… +8 more, He L, Liu K, Tang W, Wang D, Gui J, Wang Y, Liu W, Jing R
J Gerontol A Biol Sci Med Sci
· 2026 May · PMID 42033013
·
Publisher ↗
Immunosenescence-the age-related decline of immune function-drives a state of chronic, sterile inflammation termed inflammaging. Far from passive deterioration, this process is actively orchestrated by distinct but inter...Immunosenescence-the age-related decline of immune function-drives a state of chronic, sterile inflammation termed inflammaging. Far from passive deterioration, this process is actively orchestrated by distinct but interconnected hallmarks: erosion of lymphoid organs, myeloid-biased hematopoiesis, accumulation of immune-evasive senescent cells, and metabolic-epigenetic reprogramming that locks cells into dysfunctional states. These core nodes form a self-perpetuating cycle that propagates pathology across multiple organ systems, fueling neurodegeneration, cancer, musculoskeletal decline, and gut dysbiosis. Critically, the field has transitioned from descriptive phenomenology to mechanism-based intervention. This review synthesizes emerging therapeutic strategies targeting specific nodes of the immunosenescence network. We examine senotherapeutics that sensitize senescent cells for immune clearance, HSC and thymic rejuvenation to restore lymphocyte production, and metabolic-epigenetic interventions to correct intracellular deficits. By integrating these insights, we propose a precision medicine framework that moves beyond broad immunosuppression toward rational combinatorial regimens. This roadmap aims to decouple protective immunity from pathological drivers, extending healthspan and redefining the paradigm of geriatric care.
Niu RZ, Zhang MY, Yang HH
… +3 more, Zeng XF, Liu J, Bao TH
J Gerontol A Biol Sci Med Sci
· 2026 Apr · PMID 42018749
·
Publisher ↗
Central nervous system (CNS) aging is a major risk factor for many disorders, including cerebrovascular disease, neurodegeneration, and amyotrophic lateral sclerosis, yet the cellular pathways driving its progression acr...Central nervous system (CNS) aging is a major risk factor for many disorders, including cerebrovascular disease, neurodegeneration, and amyotrophic lateral sclerosis, yet the cellular pathways driving its progression across CNS regions remain poorly defined. Here we present a single-nucleus transcriptomic atlas spanning 7 human CNS regions, comprising ∼1.0 million nuclei from 235 postmortem samples derived from 200 neurologically and psychiatrically normal donors aged 19-101 years. Across regions, we delineate both shared and region-specific features of CNS aging, integrating analyses of transcriptional noise, programmed cell-death signatures, disease associations, metabolic reprogramming, and transcriptomic remodeling. We identify cross-regional vulnerability of astroglia, oligodendrocytes, and excitatory and inhibitory neurons, and show that microglial and astrocytic activation represents a broadly conserved aging response across the CNS, highlighting potential targets for intervention. Finally, we present within-dataset proof-of-concept predictive modeling use cases based on aging-associated gene signatures, providing a resource for within-atlas prioritization and hypothesis generation of candidate biomarkers of CNS aging. Together, this work offers a region-by-region map of the aging human CNS and informs the selection of specific cell types and/or regions for future anti-aging strategies.
Caro-Vega Y, Belaunzarán-Zamudio PF, Hernández-Ruiz V
… +2 more, Mosqueda JL, Avila-Funes JA
J Gerontol A Biol Sci Med Sci
· 2026 May · PMID 42018736
·
Publisher ↗
We compared the frequency of geriatric syndromes and comorbidities between women and men over 50 years of age receiving HIV care in Mexico and explore their associated characteristics. This cross-sectional study was cond...We compared the frequency of geriatric syndromes and comorbidities between women and men over 50 years of age receiving HIV care in Mexico and explore their associated characteristics. This cross-sectional study was conducted from 2012 to 2017 in Mexico. We assessed non-communicable diseases (NCDs), disability, depressive symptoms, neurocognitive impairment, frailty, polypharmacy, falls, and visual and hearing impairment. We compared the prevalence of these syndromes by sex. We fitted multivariate logistic models to identify the association of sex with the presence of NCDs and geriatric syndromes. We enrolled 616 participants, including 114 (18.5%) women. Women were older (median 57 vs 56 years old, p = .032) and had lower educational attainment (6 vs 12 years, p < .001) than men. There were no sex differences in current viral suppression (86% vs 85%, p = .78) and median CD4 cell counts (508 vs 458, p = .27). Women had a higher prevalence of any NCDs (67% vs 55%, p = .02), falls: (44% vs 26%, p < .001), depressive symptoms (15% vs 7.6%, p = .02), and frailty (9.6% vs 3.2%, p = .047) than men. In adjusted analyses, women had higher odds of frailty (aOR 4.38, 95% CI, 1.7-11.0, p = .01), falls (aOR: 1.97, 95% CI, 1.18-3.28, p < .01), NCDs (aOR: 2.03, 95% CI, 1.27-3.23, p < .01) and depression (aOR: 2.35, 95% CI, 1.17-4.61, p < .01). Older women living with HIV in Mexico experience a high prevalence of overweight/obesity, falls, comorbidity, depressive symptoms, frailty, and disability disproportionately affect women. Women were at higher risk of frailty, falls, comorbidity, and depressive symptoms, independently of age, current CD4 cell counts, and education level.
Valenzuela PL, Sánchez-Sánchez JL, Bensadoun P
… +5 more, Lemaître JM, Furman D, Vellas B, Sourdet S, de Souto Barreto P
J Gerontol A Biol Sci Med Sci
· 2026 May · PMID 42015353
·
Publisher ↗
Chronic inflammation is a hallmark of aging, but its association with indicators of healthy aging such as intrinsic capacity (IC) and functional ability remains unknown. We explored the association of an inflammation-bas...Chronic inflammation is a hallmark of aging, but its association with indicators of healthy aging such as intrinsic capacity (IC) and functional ability remains unknown. We explored the association of an inflammation-based aging clock (iAge) with these indicators in older adults. Using data from the COGFRAIL cohort, we analyzed 226 participants (82.5 ± 5.1 years, 64% women) with prefrailty/frailty and mild cognitive and functional impairment. Biological age acceleration was measured at baseline through the inflammatory clock iAge (BAAiAge). Functional ability on basic (BADL) and instrumental activities of daily living (IADL) as well as IC (a composite score [from 0 to 100] including the locomotion, cognition, psychology, sensory and vitality domains) were determined at baseline and during a 24.5-month follow-up. During the follow-up, a significant decline was observed in BADL (β = -0.4, 95% confidence interval -0.5 to -0.3, p < 0.001), IADL (β = -1.5; 95% CI = -1.7 to -1.2, p < 0.001) and IC (β = -2.0, 95% CI = -3.7 to -0.3, p = 0.025). Although baseline IC was positively associated with both BADL and IADL in cross-sectional (p = 0.002 and p < 0.001) and longitudinal analyses (p = 0.011 and p = 0.070), no association was found between BAAiAge and any of BADL/IADL, IC or IC domains in cross-sectional or longitudinal analyses. BAAiAge seems not to be associated with IC or functional ability in this cohort of very old adults with mild cognitive and functional impairment. Future research should confirm these findings in other cohorts with varying functional status.
Ede Sarıkaya B, Ateş S, Kaman T
… +1 more, Şakul AAS
J Gerontol A Biol Sci Med Sci
· 2026 May · PMID 42011111
·
Full text
BACKGROUND: Sleep disturbances and cognitive decline frequently coexist in older adults and are associated with adverse health outcomes. Aromatherapy has emerged as a potential non-pharmacological intervention; however,...BACKGROUND: Sleep disturbances and cognitive decline frequently coexist in older adults and are associated with adverse health outcomes. Aromatherapy has emerged as a potential non-pharmacological intervention; however, evidence from inhalation-based protocols integrating both subjective and objective sleep assessments remains limited. METHODS: This single-blind, randomised controlled trial was conducted in a residential care facility in Istanbul between January and June 2024. Sixty participants aged ≥65 years were randomly allocated to an intervention group (n = 30) or a control group (n = 30). The intervention consisted of inhaling a peppermint-palmarosa blend in the morning and a nighttime blend of vetiver, cedarwood, clary sage, petitgrain, and grapefruit oils for 10 minutes daily over 30 days. Outcomes included the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Blessed Orientation-Memory-Concentration Test, alongside objective sleep parameters obtained from Oppo Watch Free wearable smartwatches using photoplethysmography and accelerometer-based algorithms. RESULTS: Compared with the control group, the intervention group demonstrated significant improvements in total sleep time (d = 1.29), Rapìd Eye Movement (REM) sleep duration (d = 1.34), and deep sleep (N3) duration (d = 1.47), along with reduced sleep latency (d = -1.12) (all p < .001). Daytime sleepiness decreased, and subjective sleep quality improved. Cognitive performance also improved, with significant gains observed in orientation, memory, and concentration, whereas no significant changes were observed in the control group. CONCLUSIONS: A circadian-aligned, multicomponent inhalation aromatherapy protocol may represent a feasible and clinically relevant complementary intervention to improve sleep architecture and cognitive outcomes in older adults residing in residential care settings. CLINICAL TRIAL REGISTRATION NUMBER: NCT06208800.
Malara A, Zucchelli A, Trevisan C
… +11 more, Testa GD, Borselli G, Castaldo A, Cherubini A, Antonelli Incalzi R, Marengoni A, Morandi A, Onder G, Leosco D, Ungar A, Prescription Day LTCFs Workgroup
J Gerontol A Biol Sci Med Sci
· 2026 May · PMID 42001215
·
Publisher ↗
BACKGROUND: Medication prescribing in long-term care facilities (LTCFs) is characterized by widespread polypharmacy and frequent exposure to potentially clinically relevant drug-drug interactions (DDIs). METHODS: Data fr...BACKGROUND: Medication prescribing in long-term care facilities (LTCFs) is characterized by widespread polypharmacy and frequent exposure to potentially clinically relevant drug-drug interactions (DDIs). METHODS: Data from the Italian Prescription Day in LTCFs 2024, a national multicenter point-prevalence study conducted in 82 LTCFs, were analyzed. Prescriptions were classified using the Anatomical Therapeutic Chemical system, and DDIs were identified using an international consensus list. Resident-level variables were assessed using validated tools, and associations with DDI burden were examined using univariate mixed-effects Poisson regression models. Facility-level organizational characteristics were described by center-level DDI burden. RESULTS: The analysis included 3174 residents (mean age 84.8 years; 74.1% women), with a mean of 7.7 prescribed drugs. Drugs acting on the nervous system, alimentary tract and metabolism, and cardiovascular system were most frequently prescribed; furosemide, paracetamol, pantoprazole, quetiapine, and macrogol were the most commonly used active substances. Overall, 42.2% of residents were exposed to at least one potentially clinically relevant DDI, most commonly involving centrally acting drugs, cumulative anticholinergic burden, serotonergic combinations, and potassium-related interactions. Higher DDI burden was associated with greater pharmacological complexity, depression, sleep disorders, cardiopulmonary disease, and behavioral and psychological symptoms of dementia, whereas older age, severe cognitive impairment, malnutrition, and dysphagia were associated with fewer DDIs. Facility-level and staffing characteristics showed limited differentiation, with assisted living facilities under-represented at higher DDI burden. CONCLUSIONS: Potentially clinically relevant DDIs are common in Italian LTCFs and are primarily associated with resident-level clinical complexity, highlighting targets for medication review and deprescribing to improve medication safety.
Lange-Maia BS, Vialle RA, Wang T
… +5 more, Zammit AR, Farfel J, Seyfried NT, Bennett DA, Buchman AS
J Gerontol A Biol Sci Med Sci
· 2026 May · PMID 41999218
·
Publisher ↗
Disabilities are common and untreatable in many older adults. This proteome-wide discovery study identified cortical proteins that may provide resilience for disabilities in older adults. Participants were 850 decedents...Disabilities are common and untreatable in many older adults. This proteome-wide discovery study identified cortical proteins that may provide resilience for disabilities in older adults. Participants were 850 decedents (mean age 89.3 years [SD: 6.6] at death, 67% female) from 2 longitudinal cohort studies with proteome-wide data collected from the dorsal lateral prefrontal cortex, indices of 10 Alzheimer's disease and related dementia (ADRD) pathologies, and measures of mobility disability, instrumental activities of daily living (IADLs), and activities of daily living (ADLs) prior to death. Linear regression models adjusting for demographics identified proteins related to each disability phenotype correcting for multiple comparisons (p < 5 × 10-6). Resilience proteins-operationalized as proteins related to residual disability after adjusting for ADRD pathologies-were aggregated into resilience index scores for each disability instrument and their associations with adverse health outcomes were tested. Exploratory functional enrichment analyses identified molecular pathways associated with resilience proteins. We identified 12 resilience proteins related to mobility disability, 215 for IADL and 291 for ADL disability. Models with resilience index scores accounted for an additional 2.7%, 3.3%, and 3.5% of the variance of mobility, IADL, and ADL disability, respectively, compared to 1.7%, 2.7%, and 2.0%, for ADRD pathologies. In exploratory analyses, key enriched Gene Ontology terms were predominantly related to mitochondrial function. Further work targeting these cortical proteins is needed to demonstrate that they provide resilience for disability in older adults and can facilitate functional independence in old age, though future work is needed to demonstrate protective mechanisms. Ultimately, targeting these proteins may lead to therapies that maintain functional independence in aging adults.
Reina-Alfonso I, Álvarez-Heredia P, Vallejo-Bermúdez IM
… +9 more, Navas-Romo A, Espinar-García M, Hassouneh F, Pérez AB, Tarazona R, Solana R, Batista-Duharte A, Molina J, Pera A
J Gerontol A Biol Sci Med Sci
· 2026 Apr · PMID 41999211
·
Full text
Aging remodels antiviral immunity, yet its influence on responses to repeated mRNA vaccination is not fully defined. We evaluated humoral and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-specific T-...Aging remodels antiviral immunity, yet its influence on responses to repeated mRNA vaccination is not fully defined. We evaluated humoral and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-specific T-cell responses in 41 adults-stratified by age (<50 vs. ≥60 years), sex, prior SARS-CoV-2 infection, and cytomegalovirus (CMV) serostatus-before and after a fourth dose of the bivalent BNT162b2 vaccine. Anti-RBD IgG titers increased in nearly all participants, with no measurable impact of age, sex, infection history, or CMV status, and baseline titers predicted post-booster antibody levels. In contrast, cellular immunity showed clear heterogeneity across aging-related variables. Although the booster enhanced IFN-γ production and reduced TNF-α-associated inflammatory activity at the cohort level, older adults and males exhibited significantly lower post-boost frequencies of IFN-γ-producing CD4+ T cells. Prior SARS-CoV-2 infection was associated with attenuated CD4+ recall responses, whereas infection-naïve and female participants showed the strongest functional gains. Immunosenescence markers were associated with reduced cellular responsiveness. CMV-related immune remodeling-including higher anti-CMV IgG levels and expansions of differentiated CD8+ subsets-correlated with diminished IFN-γ responses in CD4+ and CD8+ T cells after boosting, suggesting that chronic CMV imprinting constrains heterologous antiviral immunity even in mid-adult life. Humoral and cellular changes were largely uncoupled, supporting the need to evaluate both arms of adaptive immunity. These findings indicate that while a fourth bivalent BNT162b2 dose reliably reinforces humoral immunity across ages, the magnitude and quality of cellular responses are shaped by age, sex, infection history, and CMV-associated immunosenescence. Incorporating immune-aging markers into vaccination strategies may improve booster efficacy in older populations.
Neto NJ, Hajj-Boutros G, Lok Ok Choo W
… +32 more, Borda MG, Prokopidis K, Rammal H, Rivas D, Samhat H, Baltasar-Fernandez I, Imani M, Dos Santos Gomes C, Rosas Carrasco O, Sim M, Pasco JA, Chabot J, Ayala-Copete AM, García-García FJ, Godard-Sebillotte C, Agnihotram R, Williams LJ, Andrianova A, Ramirez-Vélez R, Connolly E, Sekhon H, Arai H, Chen LK, Faust A, Bergman H, Papaioannou A, Gaudreau P, Alexandre TDS, Rodriguez-Mañas L, Oliveira Guerra R, Duque G, Transforming Health and Resilience for Healthy Lives (THRIVE) Project Group
J Gerontol A Biol Sci Med Sci
· 2026 May · PMID 41992814
·
Full text
Intrinsic capacity (IC) is defined as the composite of physical and mental abilities an individual possesses, encompassing 5 domains: cognition, psychological health, sensory function, vitality, and locomotion. This cons...Intrinsic capacity (IC) is defined as the composite of physical and mental abilities an individual possesses, encompassing 5 domains: cognition, psychological health, sensory function, vitality, and locomotion. This construct is central to the World Health Organization's framework for assessing functional ability in older adults. Growing evidence highlights the critical role of the musculoskeletal system in maintaining these domains, while conditions such as sarcopenia, osteoporosis, and their coexistence as osteosarcopenia (OS) are increasingly associated with IC decline. This narrative review compiles current evidence on the modulatory role of muscles and bones in IC and the impacts of sarcopenia, osteoporosis, and OS. Most findings suggest that musculoskeletal tissues influence IC not only through biomechanical functions but also as secretory organs, releasing myokines and osteokines with endocrine, paracrine, and autocrine effects. Among the most studied are brain-derived neurotrophic factor, irisin, osteocalcin, and interleukin-6. Dysregulation of these pathways, along with biomechanical dysfunction and systemic inflammation, links sarcopenia, osteoporosis, and OS to IC impairment. Further research is needed to clarify the specific mechanisms involved, particularly in the sensory and vitality domains, to inform targeted interventions that promote healthy aging.
Ferrara MC, Zambom-Ferraresi F, Ribera A
… +10 more, Morilla-Ruiz I, Espinoza-Tofalos S, Castellano-Tejedor C, Majó-Llopart J, Planesas-Pérez O, Heras E, Tarazona-Santabalbina FJ, Badani H, Martínez-Velilla N, Inzitari M
J Gerontol A Biol Sci Med Sci
· 2026 Apr · PMID 41992809
·
Full text
BACKGROUND: Frailty is a prognostic determinant in older patients, yet the most effective tools to predict survival remain unclear. This study aimed to assess the predictive performance of different frailty assessment to...BACKGROUND: Frailty is a prognostic determinant in older patients, yet the most effective tools to predict survival remain unclear. This study aimed to assess the predictive performance of different frailty assessment tools for 1-year mortality in the oncogeriatric population. METHODS: A multicenter cohort study (PROFIT Study) involved patients aged ≥65 with cancer, evaluated in oncology clinics and post-acute oncogeriatric units. Frailty was measured using the Geriatric 8 questionnaire (G8), Short Physical Performance Battery (SPPB), and the Frailty Index Indice Frágil-Valoración Integral Geriátrica (IF-VIG). One-year mortality was monitored. Predictive ability was analyzed using receiver operating characteristic curves with optimized cut-offs, and covariate-adjusted Cox regression models were used to evaluate the association between frailty and mortality. RESULTS: Among 229 patients (mean age 75.1 ± 6.4 years; 68.6% male; cancer type: 47.2% lung cancer, 17.9% colorectal, 25.3% other gastrointestinal, 9.6% prostate; tumoral stage IV: 85.2%), 146 (63.7%) died within 1 year. All tools showed predictive value, with IF-VIG demonstrating the highest sensitivity and SPPB the highest specificity. Optimized cut-offs improved performance compared to standard thresholds (G8: 12.5 vs 14; SPPB: 8 vs 9; IF-VIG: 0.16 vs 0.25). Adjusted Cox models confirmed significant associations with 1-year mortality: hazard ratio [HR] 1.97 (95% CI 1.30-2.99) for G8, 2.35 (95% CI 1.52-3.64) for SPPB, and 2.42 (95% CI 1.50-3.90) for IF-VIG. CONCLUSIONS: All frailty tools were significantly associated with 1-year mortality. SPPB and IF-VIG outperformed G8 in prognostic accuracy, highlighting their potential utility in clinical decision-making for older patients with cancer.
Sun Q, Zheng Z, Wu Q
… +7 more, Zhong M, Wu M, Xie R, Lai L, Chen Q, Pan X, Guan J
J Gerontol A Biol Sci Med Sci
· 2026 May · PMID 41981742
·
Publisher ↗
Recent research indicates a strong link between synaptic dysfunction and Parkinson's disease (PD). This study utilizes summary data-based Mendelian randomization (SMR) to explore genetic associations and causal relations...Recent research indicates a strong link between synaptic dysfunction and Parkinson's disease (PD). This study utilizes summary data-based Mendelian randomization (SMR) to explore genetic associations and causal relationships between synaptic genes and the risk of developing PD. This study utilized the GeneCards database to gather synaptic genes. Subsequently, we integrated QTL data related to these genes, encompassing DNA methylation (mQTLs), gene expression (eQTLs), and protein expression (pQTLs). GWAS data on PD were acquired from the GWAS Catalog, with validation datasets from the FinnGen dataset. The SMR method was used to assess potential causal relationships, and colocalization analysis was performed to verify that the signals were due to shared genetic variants, thereby enhancing the robustness of the findings. Furthermore, 5 tissue eQTL datasets were used for tissue-specific validation. Through SMR and colocalization analyses, we identified 67 methylation sites corresponding to 33 genes in mQTLs, 10 genes in eQTLs, and 4 proteins in pQTLs associated with PD. Integration of multi-omics evidence highlighted Adhesion Molecule With Ig Like Domain 1 (AMIGO1) as a potentially key gene in the association between synapses and PD, with positive SMR results in both mQTL-eQTL analysis and eQTL-pQTL analysis. The tissue-specific validation results further underscore the critical role of AMIGO1 in the disease. Our study emphasizes the importance of synaptic genes, particularly AMIGO1, in the pathogenesis of PD. Future research should build on these findings by elucidating the specific mechanisms of these genes through functional experiments, with the ultimate goal of developing effective prevention and treatment strategies.
J Gerontol A Biol Sci Med Sci
· 2026 Apr · PMID 41968832
·
Full text
Aging is a multifactorial process involving cumulative cellular and molecular damage, directly affecting physiological reserve and homeostasis. In this context, frailty emerges as a complex, dynamic, and potentially reve...Aging is a multifactorial process involving cumulative cellular and molecular damage, directly affecting physiological reserve and homeostasis. In this context, frailty emerges as a complex, dynamic, and potentially reversible geriatric syndrome, associated with inflammatory dysregulation, immunosenescence, and genetic alterations. This narrative review presents the most recent findings linking frailty to genetic factors, including genome-wide association studies and specific polymorphisms related to inflammation. The genetic relationship between frailty and various chronic comorbidities is also explored. This genetic perspective provides a promising framework for a better understanding of the etiopathogenesis of frailty and highlights new opportunities for individualized interventions.
J Gerontol A Biol Sci Med Sci
· 2026 Apr · PMID 41967082
·
Full text
BACKGROUND: The optimal glycemic target for older adults with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) remains controversial. This study analyzed longitudinal HbA1c trajectories to compare glycemi...BACKGROUND: The optimal glycemic target for older adults with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) remains controversial. This study analyzed longitudinal HbA1c trajectories to compare glycemic-mortality associations between older and younger adults, providing real-world evidence for individualized glycemic management. METHODS: This retrospective multicenter cohort study utilized the Tianjin Health and Medical Big Data Super Platform (2000-2025), including 2037 older adults as the primary cohort and 6075 younger adults as controls. Group-based trajectory modeling identified latent HbA1c evolution patterns. LASSO regression, multivariate Cox proportional hazards models, and Kaplan-Meier curves assessed mortality associations. A 5-trajectory model refined the optimal glycemic range, with robustness confirmed through subgroup and sensitivity analyses. RESULTS: Over a median follow-up of 4.56 years, 213 deaths (10.5%) occurred in older adults. Three trajectories were identified: low-stable (38.5%, mean HbA1c 5.12%), medium-declining (40.9%, 6.62%), and high-stable (20.6%, 8.50%). In younger adults, both high-stable and medium-declining trajectories were associated with increased mortality risk; in older adults, only the high-stable trajectory significantly elevated risk (HR 1.73, p = .006). Five-trajectory analysis demonstrated that maintaining HbA1c between approximately 6.66%-7.94% did not increase mortality risk, whereas progressive hyperglycemia ≥8.20% significantly increased risk (HR 1.75, p = .021). Effective glycemic reduction mitigated hyperglycemia-associated harm. CONCLUSIONS: Older adults with T2DM and CKD exhibit distinct glycemic-mortality patterns compared to younger patients. Maintaining HbA1c between 6.5%-8% was associated with optimal survival outcomes, whereas sustained hyperglycemia exceeding 8% warrants active intervention. Individualized relaxed glycemic targets may optimize the balance between survival benefit and treatment burden in this population.
J Gerontol A Biol Sci Med Sci
· 2026 Apr · PMID 41967074
·
Publisher ↗
BACKGROUND: Long-term exposure to fine particulate matter (PM2.5) increases atherosclerotic cardiovascular disease (ASCVD) risk, but evidence on its components' effects and the potential benefits achievable through PM2.5...BACKGROUND: Long-term exposure to fine particulate matter (PM2.5) increases atherosclerotic cardiovascular disease (ASCVD) risk, but evidence on its components' effects and the potential benefits achievable through PM2.5 interventions remains limited. METHODS: We used data from participants in the China Health and Retirement Longitudinal Study with low ASCVD risk at baseline. The associations between PM2.5, its components (black carbon, ammonium, nitrate, sulfate, organic matter), and 10-year ASCVD risk were evaluated using the generalized linear regression. Co-exposure effects of PM2.5 components were estimated using weighted quantile sum regression and quantile g-computation. Effects of hypothetical PM2.5 interventions (reducing annual averages to 35, 25, and 15 μg/m3) on ASCVD risk were assessed using the parametric g-formula. RESULTS: Each 10 μg/m3 increase in PM2.5 raised 10-year ASCVD risk by 18.3% (RR = 1.183, 95% CI: 1.099-1.267). Each 0.1 μg/m3 increase in black carbon and 1 μg/m3 increase in ammonium, nitrate, sulfate, and organic matter increased risks by 18.4%, 10.7%, 6.8%, 9.0%, and 6.7%, respectively. Nitrate contributed most (46.3%). Parametric g-formula estimated that reducing PM2.5 to 35, 25, and 15 μg/m3 lowered ASCVD risk by 2.78%, 3.15%, and 3.43%, respectively. Psychological conditions (e.g., depression) mediated 10-year ASCVD risk. Interaction analysis showed females were more susceptible to PM2.5 and its components. CONCLUSIONS: Long-term exposure to PM2.5 and its components elevates ASCVD risk in Chinese adults, with greater susceptibility in females. Reducing PM2.5 concentrations significantly mitigates ASCVD risk.