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

Background: Obesity increases risks for mobility limitations and disability in older adults. We examined the long-term effects of an intensive lifestyle intervention (ILI) versus diabetes support and education (DSE) and body mass index (BMI) on disability.

Methods: Disability was assessed using the Pepper Assessment Tool for Disability (PAT-D) over four post-trial visits in Look AHEAD participants with type 2 diabetes and overweight/obesity. Disability and severe disability were defined as self-reporting "a lot of difficulty" or "unable" to perform ≥1 and ≥3 activities, respectively, on PAT-D subscales for mobility, instrumental, and basic activities of daily living (IADLs and BADLs). Associations between intervention group and BMI with disability prevalence were analyzed with GEE regression models, adjusting for demographics, multimorbidity index, cognition, physical performance, and diabetes control.

Results: Among 1191 participants at the first post-trial visit, mean (±SD) age was 68.7 ± 5.7 years, BMI was 34.4 ± 6.1 kg/m2; 61% were female, 69% White, and 52% assigned to ILI. Over nine years of follow-up, odds of severe mobility disability were higher for ILI participants aged ≥70 years (OR [95% CI]): 1.50 [1.02-2.20]) but lower for those in ILI <70 years (0.69 [0.48-0.99]) compared to controls (interaction P = 0.0043). Participants with BMI ≥35 kg/m2 had higher odds of mobility disability (2.06 [1.57-2.70]), severe mobility disability (2.52 [1.79-3.56]), and IADL disability (OR [95% CI]: 2.15 [1.53-3.02]) compared to those with BMI <30 kg/m2.

Conclusion: ILI was associated with greater severe mobility disability in participants ≥70. Regardless of age, those with higher BMI had increased late-life mobility and IADL disability.

Background: Preoperative frailty assessment is crucial for surgical risk stratification in older adults. Traditional frailty measurements are often too time-consuming and resource-intensive in preoperative settings. This study aimed to externally validate an artificial intelligence (AI)-based frailty index developed using electronic health records (EHR).

Methods: We externally validated an AI-based frailty index, previously developed by our team, on a cohort of 1 52 364 surgical patients aged 65+ years from the OneFlorida+ Clinical Research Consortium. We examined the association between the predicted frailty and three postoperative outcomes: 30-day mortality, length of hospital stay, and discharge disposition. We also compared the predictive performance of general and service-specific frailty indices (the latter developed using data from patients undergoing specific surgeries) in predicting postoperative outcomes.

Results: The AI-based frailty index demonstrated a strong and stepwise association with adverse postoperative outcomes. Patients in the highest frailty level (top 20%) had significantly higher odds of 30-day mortality (OR 4.33, 95% CI 3.91-4.80), longer hospital stays (2.53 times longer, 95% CI 2.47-2.60), and a higher likelihood of unfavorable discharge dispositions compared to the lowest frailty level, after adjusting for demographics and comorbidities. The general frailty index performed comparably to or slightly better than service-specific indices across surgical specialties.

Conclusion: The developed preoperative frailty index effectively predicts postoperative outcomes in a large and diverse external cohort. The index's efficiency and predictive performance in stratifying surgical risk can potentially improve surgical care and outcomes.

Background: Intrinsic capacity (IC) is a multidimensional concept within the World Health Organization framework for healthy aging. It refers to the composite of an individual's physical and mental capacities that enable them to maintain well-being, functional ability, and engagement in valued activities throughout life. While substantial evidence supports the biological basis of IC and its subdomains, the extent to which genetic factors influence IC remains largely unexplored, with no studies currently available.

Methods: Using datasets from the UK Biobank (UKB; N = 44 631) and the Canadian Longitudinal Study on Aging (CLSA; N = 13 085), we implemented the restricted maximum likelihood method to estimate SNP-based heritability (h2snp), followed by a Genome-Wide Association Study (GWAS) to identify genetic variants associated with IC, and post-GWAS analyses to pinpoint biological implications.

Results: The h2snp for IC was estimated at 25.2% in UKB and 19.5% in CLSA. Our GWAS identified 38 independent SNPs for IC across 10 genomic loci and 4289 candidate SNPs, mapped to 197 genes. Post-GWAS analysis revealed the role of these genes in cellular processes such as cell proliferation, immune function, metabolism, and neurodegeneration, with high expression in muscle, heart, brain, adipose, and nerve tissues. Of the 52 traits tested, 23 showed significant genetic correlations with IC, and a higher genetic loading for IC was associated with higher IC scores.

Conclusions: Overall, this study provides comprehensive evidence on the genetic architecture of IC, identifying novel genetic variants and biological pathways, advancing our current knowledge and laying the foundation for ongoing and future research on healthy aging.

Background: Poor olfaction may be associated with incident heart failure (HF) in older adults, but empirical evidence is scant.

Methods: We included 5217 participants free of clinical HF and with a smell assessment in 2011-2013 from the Atherosclerosis Risk in Communities Study. Olfaction was measured by the 12-item Sniffin' Sticks odor identification test and defined as good (score 11-12), moderate (9-10), or poor (≤8). Participants were followed until the first HF hospitalization, death, last contact, or December 31, 2020, whichever happened first. We estimated adjusted risk ratios (aRR) for associations of olfaction with incident HF and its subtypes, and cross-sectional associations of olfaction with subclinical HF markers, including N-terminal pro-B-type natriuretic peptides (NT-proBNP), high-sensitive cardiac troponin T (hs-cTnT), and echocardiogram-defined structural heart disease.

Results: During a median 8.4-year follow-up, we identified 622 incident HF, including 212 with reduced ejection fraction (HFrEF) and 250 with preserved EF (HFpEF). Comparing poor with good olfaction, the aRR of HF was 1.24 (95% confidence interval (CI): 1.03,1.51) at year 8. Moderate olfaction showed a similar association pattern with HF risk, with the corresponding aRR of 1.23 (95% CI, 1.00-1.50). Poor olfaction appeared to have an evident association with HFrEF but not with HFpEF. Poor olfaction was associated with higher median levels of NT-proBNP and hs-cTnT, and higher odds of having structural heart disease than good olfaction.

Conclusions: In older adults, poor olfaction identified by a single smell test was associated with a modestly higher risk of HF, especially HFrEF, and with known subclinical HF biomarkers.

Background: Subtle biological changes related to frailty may be undetected by standard clinical methods, and reliable biomarkers for frailty are still under investigation. This study was conducted to profile plasma metabolite patterns associated with frailty and validate the most significant metabolite for identifying and predicting frailty in cross-sectional and longitudinal analyses.

Methods: The "Fujian Prospective Aging Cohort" (ChiCTR 2000032949) enrolled 2,265 community-dwelling individuals aged 60 and above in 2020. Plasma metabolites were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Frailty was assessed using Fried's phenotype and the Frailty Index.

Results: Widely targeted metabolomic analysis identified 889 metabolites. GAA was identified as the top frailty-associated candidate by ROC analysis and validated in a large cross-sectional cohort (AUC = 0.670). This cohort (N = 1,972) confirmed that subjects with lower GAA levels had a higher prevalence of frailty (P < .001). Multinomial logistic regression showed that higher GAA levels were significantly associated with lower odds of prefrailty and frailty; the ORs were 0.46 (95% CI: 0.32-0.66), and 0.15 (95% CI: 0.07-0.33) in the highest quartile, both P < .001). Over a 3-year follow-up period, a group-based trajectory model identified three Frailty Index trajectories: low-elevated (59.6%), moderate-elevated (34.1%), and high-elevated (6.3%). Subjects in the highest GAA quartile had a 36% and 66% lower likelihood of following moderate-elevated and high-elevated Frailty Index trajectories (P = .016 and P = .022).

Conclusions: This study identifies GAA as a potential metabolic biomarker for frailty. Higher GAA levels are associated with lower frailty odds and provide predictive value for a lower likelihood of frailty progression.

Senescent cardiac fibroblasts (CFs), which are activated and acquire a profibrotic phenotype, exacerbate age-related interstitial fibrosis and cardiac dysfunction by unclear mechanisms. Traditionally regarded as a central organ involved in regulating aging, the small intestine (SI) communicates with remote organs. However, the mechanisms underlying its role in CFs senescence remain undefined. We aimed to clarify whether the SI epithelium-derived exosomes (SI-exos) and their contained microRNAs could regulate CFs senescence and participate in deteriorating cardiac fibrosis during aging. Systemic administration of aged SI-exos exerted deleterious effects on the hearts of young recipient mice, as evidenced by exacerbated cardiac aging, inflammation, fibrosis, and the resulting poorer cardiac function. In vitro studies revealed that aged SI-exos could induce the activation and senescence of young CFs, while treatment with young SI-exos mitigated the activation and senescence of aged CFs. Mechanistic investigation identified that miR-223-3p was a common molecule significantly increased both in aged SI-exos and aged serum-exos. Incubation of young CFs with miR-223-3p mimics exacerbated cellular activation and senescence by cooperatively suppressing target genes: RASA1 and KLF15. In contrast, miR-223-3p inhibitor could rescue D-gal-induced CFs activation and senescence. Overexpression of RASA1 or KLF15 significantly rescued miR-223-3p-induced CFs activation and senescence. Summarily, our findings demonstrate for the first time that miR-223-3p enrichment in aged SI-exos, and its suppression of RASA1 and KLF15 in CFs, is a novel potential mechanism exacerbating cardiac aging and fibrosis. Targeting miR-223-3p mediated pathological communication between the aged SI epithelium, and CFs might be an effective strategy for cardioprotection during aging.

Background: Chronological age is an important component of medical risk scores and decision-making. However, there is considerable variability in how individuals age. We recently published an open-source deep learning model to assess biological age from chest radiographs (CXR-Age), which predicts all-cause and cardiovascular mortality better than chronological age. Here, we compare CXR-Age to 2 established epigenetic aging clocks (First generation-Horvath Age; Second generation-DNAm PhenoAge) to test which is more strongly associated with cardiopulmonary disease and frailty.

Methods: Our cohort consisted of 2097 participants from the Project Baseline Health Study, a prospective cohort study of individuals from 4 US sites. We compared the association between the different aging clocks and measures of cardiopulmonary disease, frailty, and protein abundance collected at the participant's first annual visit using linear regression models adjusted for common confounders.

Results: We found that CXR-Age was associated with coronary calcium, cardiovascular risk factors, worsening pulmonary function, increased frailty, and abundance in plasma of 2 proteins implicated in neuroinflammation and aging. Associations with DNAm PhenoAge were weaker for pulmonary function and all metrics in middle-age adults. We identified 13 proteins that were associated with DNAm PhenoAge, one (CDH13) of which was also associated with CXR-Age. No associations were found with Horvath Age.

Conclusions: These results suggest that CXR-Age may serve as a better metric of cardiopulmonary aging than epigenetic aging clocks, especially in midlife adults.

Both mosaic loss of Y chromosome (mLOY) and frailty are related to human aging. However, their relationship and the potential mediating effect of mLOY on the association between frailty and mortality risk remain understudied. A total of 8947 middle-aged and older male adults from the Dongfeng-Tongji cohort were included in this study. Causes of death were tracked till the end of year 2018. Frailty index (FI) was calculated by 34 deficits and categorized into three groups: (1) robust (FI ≤ 0.10), (2) prefrail (0.10 < FI < 0.25), and (3) frail (FI ≥ 0.25). mLOY was estimated by genotyping data and presented as the proportion of leukocytes with mLOY. Cox proportional hazards regressions were used to assess the associations of mLOY with risk of mortality. Mediation effects of mLOY were estimated under a counterfactual-based framework. In this prospective study, the prevalence of prefrail and frail participants were 50.2% and 29.0%, respectively. Compared to the robust participants, frail males exhibited significantly increased level of mLOY [β (95% CI) =1.15 (0.62 to 1.68)]. Frailty and mLOY showed significant associations with increased mortality risks, and mLOY may mediate a separate 27.3, 53.9, and 23.5% of the association of frailty with the risks of death from all causes, cancer, and other causes. These relationships were confined to males aged ≥ 65 years. These findings unveiled the relationships of frailty with mLOY and the mediation role of mLOY in the frailty-mortality association among older males aged ≥ 65 years. Our results highlighted the importance of mLOY during male aging.

Background: Epigenetic age acceleration (EAA), reflecting the difference between biological and chronological age, serves as a novel biomarker for biological aging. Evidence shows metabolic syndrome (MetS) affects aging-related physiology, but the relationship between MetS and EAA remains unclear and warrants further investigation.

Methods: We analyzed data from 1972 individuals in the National Health and Nutrition Examination Survey (NHANES) 1999-2002. EAAs were determined from the residuals of 13 epigenetic clocks regressed on chronological age. Weighted logistic regression, linear regression, and restricted cubic spline (RCS) models were utilized to investigate correlations between EAAs and MetS. Genetic correlation and two-sample Mendelian randomization (MR) analyses were performed to assess causal associations, complemented by summary-data-based Mendelian randomization (SMR) and bioinformatics analyses to explore gene regulation related to these associations.

Results: Participants with MetS exhibited significantly higher levels of EAAs, with DNA methylation (DNAm) PhenoAge acceleration (PhenoAgeAccel) increasing by 0.84 years (95% CI: 0.04-1.64), DNAm GrimAge acceleration (GrimAgeAccel) increasing by 0.83 years (95% CI: 0.32-1.34), and DNAm Grim2Age acceleration (GrimAge2Accel) increasing by 1.33 years (95% CI: 0.77-1.89). Elevated EAAs were significantly associated with increased risks of MetS, a correlation further substantiated by RCS models. Genetic correlation and MR analyses revealed significant associations between MetS and GrimAgeAccel. SMR identified shared risk genes between MetS and GrimAgeAccel. Subsequent bioinformatics analyses showed that these genes were associated with phenotypes such as glucose-dependent proinsulinotropic peptide levels.

Conclusion: We established a causal relationship between MetS and EAAs, indicating that MetS may provide new strategies for personalized aging prevention and intervention.

Background: The Fourth and Fifth Industrial Revolutions have introduced new and innovative technologies, such as artificial intelligence and virtual humanoids (VH) that offer promising solutions to health challenges among older adults. This project aims to provide an integrative review of VH concepts in geriatric care.

Methods: Scientific articles from reputable research databases (eg, Scopus, Web of Science, and PubMed) were extracted using relevant keywords and uploaded to the Covidence application for screening, full-text analysis, and extraction. A total of 36 articles were generated in the final stage of screening.

Results: The 36 articles showcased various findings and insights on VH for geriatric care. More than half of the articles (66.67%) originated from the European region and were published in technology-related journals (55.56%). Most VH in the studies are used for social health interventions (33.3%), specifically for companionship purposes (25%). Furthermore, a great number of VH have average human likeness (55.56%) with the capacity to communicate with the end-user using pre-programmed responses (33.33%).

Conclusions: The use of VH in geriatric care has shifted from providing companionship (social) to delivering relevant instructions (educational) for health and well-being. Researchers from developing countries are providing increasing attention to VH studies involving multidisciplinary and interdisciplinary teams. The use of AI in VH development is limited, but it has the potential to transform geriatric care and the field of gerotechnology.