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

Background: The association between subclinical cardiovascular disease (CVD) and cognitive decline in hypertensive adults and the underlying brain pathologies remain unclear. It is also undetermined whether intensifying blood pressure (BP) treatment slows down cognitive decline associated with subclinical CVD.

Methods: We conducted a post hoc analysis of the Systolic Blood Pressure Intervention Trial. Subclinical CVD at baseline was identified by elevated levels of high-sensitivity cardiac troponin T (hs-cTnT ≥ 14 ng/L) and N-terminal pro-B-type natriuretic peptide (NT-proBNP ≥ 125 pg/mL). Global cognitive function and domain-specific measures (memory, processing speed, language, and executive function) were assessed at baseline and follow-up (years 2, 4, and 6) in 2 733 participants. White matter lesions, cerebral blood flow, and brain tissue volume were assessed by MRI at baseline and year 4 in a subset of 639 participants.

Results: Both elevated hs-cTnT and NT-proBNP levels at baseline were associated with accelerated cognitive decline across all domains after adjusting for potential confounding factors. The group with elevated levels of both cardiac biomarkers showed the fastest decline, with a larger annual decline rate of 0.033 (95% CI: 0.024-0.041) in the z-score of global cognitive function compared with the group with normal levels. Elevated levels of both biomarkers were also associated with a faster progression in white matter lesions, but not with changes in total brain tissue volume or cerebral blood flow. Intensive BP treatment did not attenuate these associations compared with standard treatment.

Conclusions: Subclinical CVD may contribute to faster white matter lesion progression and accelerated cognitive decline in patients with hypertension, regardless of intensive BP treatment.

Background: Intrinsic capacity (IC) is the composite of an individual's physical and mental capacities. However, the association between IC trajectories and falls and hospitalizations remains uncertain. This study aimed to determine the IC trajectories among older adults, investigating its association with subsequent risk of falls and hospitalizations.

Methods: This study enrolled 3 902 older adults aged ≥65 from the National Health and Aging Trends Study (Wave 2015-2019). A bifactor model was used for repeated measurements of the 5 IC domains to generate IC scores for 4 time points (Wave 2015-2018). IC trajectories were identified using group-based trajectory modeling, and modified Poisson regression was used to analyze the associations between IC trajectories and subsequent fall and hospitalization risk.

Results: The mean age of the participants was 76.70 years (standard deviation = 6.78), and the majority were female (57.3%). Three IC trajectories were identified, including persistently low (17.86%), persistently moderate (33.96%), and persistently high (48.18%). Compared with the persistently low class, the moderate and high classes have significantly lower fall and hospitalization risks. Multivariate-adjusted rate ratios fall occurrence were 0.87 (95% confidence interval [CI]: 0.78-0.98) and 0.74 (95% CI: 0.65-0.85), for multiple falls were 0.81 (95% CI: 0.68-0.96) and 0.52 (95% CI: 0.41-0.66), for hospitalization occurrence were 0.76 (95% CI: 0.66-0.87) and 0.48 (95% CI: 0.39-0.58), and for multiple hospitalizations were 0.65 (95% CI: 0.53-0.80) and 0.37 (95% CI: 0.28-0.48), respectively.

Conclusions: IC trajectories were associated with falls and hospitalizations. Strategies focusing on improving and maintaining IC at a higher level over time could help reduce the subsequent risk of falls and hospitalizations.

Background: Wearable sensors that monitor physical behaviors are increasingly adopted in clinical research. Older adult research participants have expressed interest in tracking and receiving feedback on their physical behaviors. Simultaneously, researchers and clinical trial sponsors are interested in returning results to participants, but the question of how to return individual study results derived from research-grade wearable sensors remains unanswered. In this study, we (1) assessed the feasibility of returning individual physical behavior results to older adult research participants and (2) obtained participant feedback on the returned results.

Methods: Older adult participants (N = 20; ages 67-96) underwent 14 days of remote monitoring with 2 wearable sensors. We then used a semiautomated process to generate a 1-page report summarizing each participant's physical behaviors across the 14 days. This report was delivered to each participant via email, and they were asked to evaluate the report.

Results: Participants found the reports easy to understand, health-relevant, interesting, and visually pleasing. They had valuable suggestions to improve data interpretability and raised concerns such as comparisons with measures derived from their consumer-grade sensors.

Conclusions: We have demonstrated the feasibility of returning individual physical behavior results from research-grade devices to older research participants, and our results indicate that this practice is well-received. Further research to develop more efficient and scalable systems to return results to participants, and to understand the preferences of participants in larger, more representative samples, is warranted.

Background: Little work to date has quantified the effect of psychotropic medications (antidepressants, benzodiazepines, "Z" drugs, antipsychotics, anticholinergics) on mobility and gait in later life. The aim of this study is to examine the relationship between these medications and mobility/gait parameters in a large cohort of community-dwelling older people.

Methods: Participants were included if they were aged ≥60 years at TILDA Wave 1 and underwent gait and mobility assessment (Gaitrite system), with follow-up at Wave 3 (4 years). Medication lists were examined for psychotropic medications. Regression models assessed the relationship between psychotropic medications and mobility using the following parameters: Timed Up and Go, gait speed, step length/width, and double support phase. Multilevel modeling assessed trajectories of mobility/gait variables over time by psychotropic use.

Results: Of 2620 patients, 12% were prescribed ≥1 psychotropic medication, and 3% prescribed ≥2 psychotropics. Cross-sectionally, psychotropic medication was independently associated with prolonged Timed Up and Go (β = 0.50 [95% confidence interval {CI} 0.27-0.73]; p < .001), slower gait speed (β = -5.65 [95% CI -7.92 to -3.38]; p < .001), shorter step length (β = -2.03 [95% CI -2.93 to -1.42]; p < .001), and increased double support phase (β = 0.47 [95% CI 0.19-0.75]; p = .001). Longitudinally, psychotropic use was independently associated with transition to abnormal Timed Up and Go (odds ratio 2.68 [95% CI 1.55-4.64], p < .001), whereas using ≥2 psychotropics was associated with transition to slower gait speed (odds ratio 2.59 [95% CI 1.01-6.68]; p = .048).

Conclusions: Psychotropic use was associated with significantly poorer mobility and gait performance, both cross-sectionally and longitudinally. It is imperative that psychotropic medication use is reviewed as part of a comprehensive geriatric assessment.

Heterogeneity in aging is a fundamental biological process arising from multifactorial etiologies, including genetic, lifestyle, and socioeconomic factors. Modeling this heterogeneity in animal systems is critical for elucidating the underlying mechanisms of aging and for leveraging these insights in translational research. Here we present part II, a summary of the model organism research presented at the NIA Heterogeneity and Successful Aging workshop, held in May 2023.

Background: Racial/ethnic minoritized groups in the United States have a higher prevalence of cardiometabolic multimorbidity and experience a higher risk of dementia. This study evaluates the relationship between cardiometabolic multimorbidity and dementia onset according to racial/ethnic group in a nationally representative cohort of U.S. middle-aged and older adults.

Methods: Data from the Health & Retirement Study (1998-2018, N = 7,960, mean baseline age 59.4 years) and discrete-time survival models were used to estimate differences in the risk of dementia onset, defined by Langa-Weir classification. Models included race/ethnicity (non-Hispanic White, non-Hispanic Black, and Hispanic), chronic disease/multimorbidity categories (no disease, one disease, cardiovascular multimorbidity, metabolic multimorbidity, cardiometabolic multimorbidity, other multimorbidity), age, sex, education, wealth, body-mass index, and proxy status.

Results: Over a mean follow-up of 14.6 years, 7.7% of the participants (n = 614) developed dementia. In the fully adjusted model, participants with cardiometabolic multimorbidity had the highest risk of dementia onset (HR:3.27, 95%CI: 2.06, 5.21), followed by metabolic (HR:1.83, 95%CI: 1.14, 2.94), and cardiovascular (HR:1.81, 95%CI: 1.24, 2.64) multimorbidity, relative to participants with no disease. The risk of dementia was significantly greater among Black (HR: 6.40, 95% CI: 3.84, 10.67) and Hispanic participants (HR: 4.90, 95% CI: 2.85, 8.43) with cardiometabolic multimorbidity, compared with White adults with no disease.

Conclusions: Individuals from racial/ethnic minoritized groups have a higher risk of dementia. The risk of dementia onset was significantly greater for Black and Hispanic participants experiencing cardiometabolic multimorbidity, highlighting the value of intervening in cardiometabolic conditions among middle-aged and older adults, in particular, those from racial/ethnic minoritized backgrounds to reduce the risk of developing dementia.

The aging process is universal, and it is characterized by a progressive deterioration and decrease in physiological function leading to decline on the organismal level. Nevertheless, a number of genetic and nongenetic interventions have been described, which successfully extend healthspan and lifespan in different species. Furthermore, a number of clinical trials have been evaluating the feasibility of different interventions to promote human health. The goal of the annual Biological Sciences Section of the Gerontological Society of America meeting was to share current knowledge of different topics in aging research and provide a vision of the future of aging research. The meeting gathered international experts in diverse areas of aging research including basic biology, demography, and clinical and translational studies. Specific topics included metabolism, inflammaging, epigenetic clocks, frailty, senescence, neuroscience, stem cells, reproductive aging, inter-organelle crosstalk, comparative transcriptomics of longevity, circadian clock, metabolomics, and biodemography.

Cellular senescence is a pivotal contributor to aging and age-related diseases. The targeted elimination of senescent cells, known as senolysis, has emerged as a promising therapeutic strategy for mitigating these conditions. Glutaminase 1 (GLS1), a key enzyme in the glutaminolysis pathway, has been implicated in various cellular senescence processes. However, its specific role in senescent renal tubular epithelial cells (TECs) remains unclear. This study investigates the role and underlying mechanisms of GLS1 in senescent TECs. Using d-galactose (d-gal)-induced senescence of HK-2 cells, we found that GLS1 inhibition eliminated senescent TECs by promoting excessive mitochondrial permeability transition pore (mPTP) opening. Mechanistically, the excessive mPTP opening is associated with the upregulation of mitofusin 1 (MFN1). Inhibition of GLS1 in d-gal-treated HK-2 cells induced a shift in mitochondrial dynamics from fission to fusion, accompanied by a significant increase in MFN1 expression. Knocking down MFN1 reduced the mPTP opening and the expression of mPTP-related genes (PPIF, VDAC, and BAX) in cells co-treated with d-gal and the GLS1 inhibitor BPTES. Moreover, treatment of aged mice with BPTES specifically eliminated senescent TECs and ameliorated age-associated kidney disease. These findings reveal that GLS1 inhibition eliminate senescent TECs by promoting excessive mPTP opening, suggesting that targeting GLS1 may be a novel senolytic strategy for alleviating aging-related kidney diseases.

Background: Emerging evidence suggests that olfactory dysfunction may be a marker of frailty, a key predictor of adverse health outcomes in aging populations. This study examines the association between olfactory impairment and frailty in older adults.

Methods: We analyzed data from 5,231 participants (mean age: 75.3 ± 5.0 years; 59% women; 22% Black) of the Atherosclerosis Risk in Communities (ARIC) Study. Olfactory function, assessed using the 12-item Sniffin' Sticks Test at Visit 5 (2011-2013), was categorized as poor (0-8), moderate (9-10), or good (11-12). Frailty status was ascertained using both the Fried Frailty Phenotype and the Cumulative Frailty Index. Cross-sectional associations between olfactory function and frailty status were examined using logistic regression and linear regression. Logistic regression was used to examine the association between olfactory function and prefrailty or frailty occurring within five years among 1,519 participants robust at baseline.

Results: In cross-sectional analyses, good olfactory function was associated with lower odds of frailty (odds ratio [OR] = 0.29, 95% confidence interval [CI]: 0.22, 0.39) and prefrailty (OR = 0.52, 95% CI: 0.45, 0.61). These associations remained robust after adjusting for covariates. Longitudinal analyses similarly showed a dose-response pattern, with improved olfaction associated with decreased odds of experiencing prefrailty (OR=0.63 95% CI [0.48, 0.83]) or frailty (OR=0.50, 95% CI [0.25, 1.02]).

Conclusions: Good, as compared to poor, olfactory function is associated with lower frailty risk in older adults, suggesting that olfactory impairment may serve as an early marker of frailty. Further research is needed to elucidate the mechanisms linking olfaction and frailty and explore potential interventions.

Background: Climate change is expected to disrupt weather patterns across the world, exposing older adults to more intense and frequent periods of hot weather. Meanwhile, lab-based studies have established a causal relationship between ambient temperature and cognitive abilities, suggesting the expected rise in temperature may influence older adults' cognitive functioning. Nevertheless, it is not clear whether, and to what extent, the temperature variations in older adults' own homes-which unlike lab settings are under their control-influence their cognitive functioning. Our objective was to provide proof of concept that home ambient temperature influences self-reported ability to maintain attention in older adults.

Methods: We conducted a longitudinal observational study, continuously monitoring the home ambient temperature and self-reported difficulty keeping attention for 12 months in 47 of community-dwelling older adults living in Boston, Massachusetts.

Results: We observed a U-shaped relationship between home ambient temperature at the time of assessment and the odds ratio (OR) of reporting difficulty keeping attention such that the OR was lowest between 20°C and 24°C and doubled when moving away from this range by 4°C in either direction.

Discussion: Our results suggest that even under the current climate, a considerable portion of older adults encounter indoor temperatures detrimental to their cognitive abilities. Climate change may exacerbate this problem, particularly among low-income and underserved older adults. Addressing this issue in public health and housing policy is essential to building climate resiliency in this vulnerable population.