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

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.

Background: To identify the most vulnerable brain regions in gray matter attributable to advanced brain aging and examine the cognitive correlates of advanced brain aging in Parkinson's disease (PD).

Methods: One hundred twenty-five early-stage PD patients with both structural, diffusion MRI and DAT-SPECT data available were included at baseline (year 0) from Parkinson's Progression Markers Initiative, with neuroimaging follow-up at year 1, 2, 4. Annual assessment of cognition was performed in 5 years. The relationships between brain-predicted age difference (PAD), free water (FW) in cortical and subcortical gray matter, and cognition were examined with linear regression and linear mixed-effects model. Cox proportional hazards model was used to investigate the relation between brain PAD and the risk of conversion to mild cognitive impairment (MCI).

Results: One hundred twenty-five PD patients with a mean (SD) chronological age of 60.99 (9.50) years and 82 (65.6%) were men. Brain PAD followed a non-linear progression pattern over time (P = .028). Brain PAD was differentially associated with FW in cortical and subcortical gray matter, with the most preferentially vulnerable regions identified as temporal cortex, striatum, hippocampus, and cholinergic basal forebrain. Baseline brain PAD was associated with cognitive deficits and the conversion to MCI during the 5-year follow-up.

Conclusions: Our findings suggest that brain PAD offers potential in pinpointing regions most susceptible to accelerated brain aging and identifying patients with Parkinson's disease who are at an increased risk of converting to mild cognitive impairment. .

Background: The "INStitute for Prevention," "healthy agIng," and "medicine REjuvenative" "Translational" (INSPIRE-T) study is a 10-year observational study. The primary objective of which is to study trajectories of aging across lifespan from the perspective of intrinsic capacity (IC) through deep clinical and biological phenotyping.

Methods: IC was assessed in the INSPIRE-T cohort stratified by age (10-year age groups) using the World Health Organization (WHO) integrated care for older people (ICOPE) program. Biospecimens (biofluids, dental plaque, nasopharyngeal swabs, stools, hair follicles, and skin biopsies) were also collected for biomarker studies and drug-target identification for the prediction and prevention of IC declines respectively.

Results: The INSPIRE-T baseline data is presented including demographic, health, anthropometric, lifestyle, and IC characteristics of the cohort. The open cohort (ongoing recruitment) currently consists of 1109 participants with data available at baseline (61.9% female) aged from 20 to 102 years old (mean age ± standard deviation: 62.4 ± 19.0 years). The most prevalent IC abnormalities identified using ICOPE Step 1. screening appeared to be in vision (89.3%), audition (30.5%), and cognition (24.7%) in the total baseline population, while locomotor capacity abnormalities (5.4%) appeared to be the least frequent. Sex-specific differences were observed for the domains of psychological well-being, audition, vitality in 30-39-year olds and vision in subjects ≤39 years old.

Conclusions: The ultimate goal of INSPIRE-T is to enable the identification of individuals at risk of IC declines in order to implement personalized preventive interventions to promote healthy aging.

Background: Walking automaticity facilitates maintenance of gait speed without prefrontal cortex (PFC) resources. Brain aging may cause shifts to attentional gait with greater engagement of the PFC. Nigrostriatal dopaminergic integrity likely facilitates walking automaticity and gait speed during attentional dual-tasks.

Methods: Older adults (n = 201; age = 74.9; 63.2% women, gait speed = 1.10 m/s) completed a dual-task protocol of saying every other letter of the alphabet while walking. PFC activation was measured by functional near-infrared spectroscopy. Four groups were defined based on PFC activation (increased during dual-task, PFC+, or not, PFC-) and gait speed performance (maintained during dual-task, gait+, or slowed, gait-). To compare nigrostriatal dopaminergic integrity across groups, we assessed binding of the type-2 vesicular monoamine transporter density in the sensorimotor and associative striatum using [11C]-(+)-a-dihydrotetrabenazine (DTBZ) positron emission tomography. Multinomial regression estimated adjusted associations of DTBZ binding with group membership. We hypothesized that DTBZ binding was highest for those who maintained gait speed without additional PFC activation when switching from single- to dual-task (PFC-/gait+; ie, highest gait automaticity).

Results: In bivariate analyses, the PFC-/gait+ group had the highest DTBZ binding in the sensorimotor striatum (P = .05); binding in the associative striatum was similar across groups (P = .1). Results were similar in adjusted regression analyses; DTBZ binding in sensorimotor striatum was associated with lower likelihood to be in the PFC-/gait- (odds ratio [OR] = 0.28; 95% CI, 0.08-0.94) or the PFC+/gait+ (OR = 0.29; 95% CI, 0.10-0.84) groups compared to PFC-/gait+ reference group.

Conclusion: These results provide support for dopaminergic involvement in sustaining gait automaticity at older ages.

Background: Research on cognition and pain is limited in Low and Middle-income Countries (LMICs) and understanding how chronic conditions and pain treatment may moderate this association is underexplored. This study aimed to explore the relationship between pain and cognition and the moderating effect of hypertension, diabetes, HIV, pain treatment, and depressive symptoms.

Methods: We analyzed data from 3803 individuals enrolled in the HAALSI study, a longitudinal population study of older adults in Agincourt, South Africa. Pain was measured with the Brief Pain Inventory. Cognition was assessed using a composite of orientation questions, a memory test, and the Trails Making Test B. Chronic conditions were assessed using biological measures, and depressive symptoms were measured using the CES-D scale. Linear regression models were used to investigate the relationship.

Results: Baseline and longitudinal pain were significantly associated with poorer episodic memory (ß = -0.17 [P < .001]; ß = -0.18 [P < .001]). Hypertension amplified the negative effect of pain on episodic memory, while diabetes and HIV did not moderate the relationship between pain and cognition (ß = -0.10 [.006]). Pain treatment was associated with poorer cognitive performance. Depressive symptoms moderated the relationship between pain and both cognition and executive function (EF) (P = .02). The negative effect of pain on episodic memory was observed in individuals with both acute and persisting pain, while it only affected EF in those with acute pain.

Conclusions: These findings highlight the importance of examining factors that may moderate the relationship between pain and cognition and strategies to mitigate the effect pain has on cognition, particularly in LMICs.