Journals of Gerontology Series A-Biological Sciences and Medical Sciences最新文献

Frailty is a geriatric syndrome characterized by age-related decline in physiological reserves and functions in multiple organ systems, including the musculoskeletal, neuroendocrine/metabolic, and immune systems. Animal models are essential to study the biological basis of aging and potential ways to delay the onset of age-related phenotypes. Unfortunately, validated animal models of frailty are still lacking in preclinical research. The senescence-accelerated prone-8 (SAMP8) mouse strain exhibits early cognitive loss that mimics the deterioration of learning and memory in the elderly and is widely used as a model of aging and neurodegenerative diseases. Here, we examined the frailty phenotype, which includes body weight, strength, endurance, activity, and slow walking speed, in male and female SAMP8 and senescence-accelerated mouse resistant (SAMR1) mice at 6- and 9-months of age. We found that the prevalence of frailty was higher in SAMP8 mice compared with SAMR1 mice, regardless of sex. The overall percentage of prefrail and frail mice was similar in male and female SAMP8 mice, although the percentage of frail mice was slightly higher in males than in females. In addition, we found sex- and frailty-specific changes in selected miRNAs blood levels. In particular, the levels of miR-34a-5p and miR-331-3p were higher in both prefrail and frail mice, whereas miR-26b-5p was increased only in frail mice compared with robust mice. Finally, levels of miR-331-3p were also increased in whole blood from a small group of frail patients. Overall, these results suggest that SAMP8 mice may be a useful mouse model for identifying potential biomarkers and studying biological mechanisms of frailty.

Background: To assess the relationship between self-reported and performance-based visual impairment (VI) and lower extremity physical function.

Methods: Cross-sectional analysis of 2 219 Health ABC participants who completed vision testing and the Short Physical Performance Battery (SPPB). Linear regression models used either self-reported (weighted visual function question [VFQ] score) or performance-based (visual acuity [VA], log contrast sensitivity [LCS], Frisby stereoacuity [SA]) to predict SPPB or its components-gait speed, chair stands, or standing balance-with and without covariate adjustment.

Results: Mean age was 73.5 years (range 69-80); 52.4% were female and 37.4% African American. All VI measures were strongly associated with SPPB in unadjusted and adjusted models (p < .001). A self-reported VFQ score 1 standard deviation lower than the mean (mean 87.8 out of 100) demonstrated a -0.241 (95% confidence interval [CI]: -0.325, -0.156) adjusted difference in SPPB. After controlling for covariates, VA of <20/40 (41%) demonstrated a -0.496 (-0.660, -0.331) lower SPPB score while SA score>85 arcsec (30%) had a -0.449 (-0.627, -0.271) adjusted SPPB score versus those with better visual function. LCS < 1.55 (28.6%) was associated with a -0.759 (-0.938, -0.579) lower and LCS ≤ 1.30 (8%) with a -1.216 (-1.515, -0.918) lower adjusted SPPB score relative to better LCS. In a final multivariable model containing multiple vision measures, LCS remained independently associated with SPPB and all components, while SA remained associated with balance (all p < .05).

Conclusions: Both self-reported and performance-based VI are strongly associated with poor lower extremity physical function. These findings may identify a subgroup of older adults with co-existing visual and physical dysfunction who may benefit from targeted screening and intervention to prevent disability.

Biological age captures a person's age-related risk of unfavorable outcomes using biophysiological information. Multivariate biological age measures include frailty scores and molecular biomarkers. These measures are often studied in isolation, but here we present a large-scale study comparing them. In 2 prospective cohorts (n = 3 222), we compared epigenetic (DNAm Horvath, DNAm Hannum, DNAm Lin, DNAm epiTOC, DNAm PhenoAge, DNAm DunedinPoAm, DNAm GrimAge, and DNAm Zhang) and metabolomic-based (MetaboAge and MetaboHealth) biomarkers in reflection of biological age, as represented by 5 frailty measures and overall mortality. Biomarkers trained on outcomes with biophysiological and/or mortality information outperformed age-trained biomarkers in frailty reflection and mortality prediction. DNAm GrimAge and MetaboHealth, trained on mortality, showed the strongest association with these outcomes. The associations of DNAm GrimAge and MetaboHealth with frailty and mortality were independent of each other and of the frailty score mimicking clinical geriatric assessment. Epigenetic, metabolomic, and clinical biological age markers seem to capture different aspects of aging. These findings suggest that mortality-trained molecular markers may provide novel phenotype reflecting biological age and strengthen current clinical geriatric health and well-being assessment.

Background: The racial and ethnic differences in trajectories of sleep disturbances in later life are crucial for addressing health disparities, but are not well understood. This study examines (a) how trajectories of sleep disturbances vary by race and ethnicity and birth cohort and (b) whether social and health risk factors explain such variations.

Methods: The study uses longitudinal data from the 2002-2018 Health and Retirement Study (N = 21 963) and the multilevel growth curve model to assess trajectories of sleep disturbances and their variations across 6 cohorts of White, Black, and Hispanic older adults. Sleep disturbances are measured using a modified Jenkins Sleep Scale.

Results: Without controls, sleep disturbances increased with aging for all racial and ethnic groups, but more rapidly among minorities, particularly younger cohorts of Hispanic older adults. When controlling for social and health risks, sleep disturbances did not change with aging for Whites and Blacks and increased for younger cohorts of Hispanics. Cohort effects were observed among White older adults, with higher sleep disturbances in younger cohorts. Importantly, the racial and ethnic disparities in age and cohort effects were not fully explained by social and health risks. Of the symptoms, the most salient racial and ethnic disparities were found in "waking up at night" and "not feeling rested."

Conclusions: Findings reveal several differences by race and ethnicity and birth cohort in trajectories of sleep disturbances. Efforts should be made to improve sleep health for older adults as they age, especially for younger cohorts of Blacks and Hispanics.

Background: Sleep behavior (eg, sleep duration, sleep quality, and nap) is closely related to many chronic conditions. However, less is known about its association with multiple chronic conditions (multimorbidity), particularly evidence from cohort studies.

Methods: Data were collected from a cohort of 8 937 individuals aged 45 and older from the China Health and Retirement Longitudinal Study (2011-2018). Sleep duration, sleep quality, and nap duration were collected in 2011 and 2013. Progression of multimorbidity was defined as the first report of 2 or more chronic conditions for participants without multimorbidity or the new report of 1 or more conditions for those with multimorbidity. Cox regression models were performed to calculate the hazard ratios and 95% confidence intervals (CIs) of the associations between sleep behaviors and the progression of multimorbidity.

Results: Short sleep duration and poor sleep quality were associated with the progression of multimorbidity independently and jointly, especially in those less than 65 years and females. The U-shaped dose-response relationships were observed between nighttime and total sleep duration and the progression of multimorbidity. Persistent short and unsteadily changed sleep behaviors increased the risk of multimorbidity progression. Individuals sleeping ≤5 h/night with 5-7 restless days/week had 1.53 times higher risk of multimorbidity progression (95% CI: 1.37-1.71), compared to those sleeping 7-8 h/night with <1 restless day/week.

Conclusions: Short sleep duration and poor sleep quality were independently and jointly associated with a higher risk of multimorbidity progression in a mid-to-older population. Optimal sleep duration and sleep quality should be emphasized in multimorbidity prevention and control.

Background: Social isolation is prevalent and associated with dementia, yet the directionality and mechanisms are less understood. This study examined the association between social isolation and cognitive functioning and explored the mediating role of sleep disturbance on the social isolation-cognition relationship.

Methods: Data from 5 753 dementia-free Americans aged ≥50 of 2006 (T1), 2010 (T2), and 2014 (T3) waves of the Health and Retirement Study. Social isolation was measured by the Steptoe Social Isolation Index. Cognitive functioning was measured by the Telephone Interview of Cognitive Status. Sleep disturbance was measured with the modified Jenkins Sleep Scale. We used cross-lagged panel models to determine the associations between social isolation, sleep disturbance, and cognitive functioning.

Results: Social isolation is significantly associated with subsequent cognitive functioning (T1 to T2: β = -0.055, standard error [SE] = 0.014, p < .001; T2 to T3: β = -0.044, SE = 0.016, p < .001). Lower cognitive functioning is significantly associated with greater subsequent social isolation (T1 to T2: β = -0.101, SE = 0.020, p < .001; T2 to T3: β = -0.058, SE = .011, p < .001). Sleep disturbance at T2 partially mediated the effect of social isolation (T1) on cognitive functioning (T3), accounting for 6.2% of the total effect (β = -0.003, SE = 0.001, p < .01).

Conclusions: Social isolation may deteriorate cognitive functioning and vice versa. The association between social isolation and cognition is partially explained by sleep disturbance.

Frailty is characterized by increased vulnerability to disability and high risk for mortality in older adults. Identification of factors that contribute to frailty resilience is an important step in the development of effective therapies that protect against frailty. First, a reliable quantification of frailty resilience is needed. We developed a novel measure of frailty resilience, the Frailty Resilience Score (FRS), that integrates frailty genetic risk, age, and sex. Application of FRS to the LonGenity cohort (n = 467, mean age 74.4) demonstrated its validity compared to phenotypic frailty and its utility as a reliable predictor of overall survival. In a multivariable-adjusted analysis, 1-standard deviation increase in FRS predicted a 38% reduction in the hazard of mortality, independent of baseline frailty (p < .001). Additionally, FRS was used to identify a proteomic profile of frailty resilience. FRS was shown to be a reliable measure of frailty resilience that can be applied to biological studies of resilience.

Although growth/differentiation factor 11 (GDF11), growth/differentiation factor 8 (GDF8), and their circulating antagonists, which include GDF11 and GDF8 propeptides, follistatin (FST), WAP, Follistatin/Kazal, Immunoglobulin, Kunitz And Netrin Domain Containing (WFIKKN)1, and WFIKKN2, have been shown to influence skeletal muscle and aging in mice, the relationship of these circulating factors with human phenotypes is less clear. This study aimed to characterize the relationship between plasma GDF8, GDF11, FST, WFIKKN1, and WFIKKN2 concentrations with the decline of grip strength in 534 adults, ≥65 years, who participated in the Baltimore Longitudinal Study of Aging and had grip strength measured over time. Plasma GDF8 and GDF11 mature proteins, GDF8 and GDF11 propeptides, FST (isoform FST315 and cleaved form FST303), WFIKKN1, and WFIKKN2 concentrations were measured using selected reaction monitoring-tandem mass spectrometry at baseline. Grip strength was measured at baseline and at follow-up visits (median follow-up 8.87 years). Mean (standard deviation) grip strength declined in men and women by -0.84 (2.45) and -0.60 (1.32) kg/year, respectively. Plasma GDF8 and GDF11 mature proteins, GDF8 and GDF11 propeptides, FST315, FST303, WFIKKN1, and WFIKKN2 concentrations were not independently predictive of the decline of grip strength in men or women in multivariable linear regression analyses that adjusted for potential confounders. In conclusion, circulating GDF8, GDF11, and their antagonists do not appear to influence the decline of grip strength in older men or women.

Background: Almost 60% of adults with amnestic mild cognitive impairment (aMCI) have obstructive sleep apnea (OSA). Treatment with continuous positive airway pressure (CPAP) may delay cognitive decline, but CPAP adherence is often suboptimal. In this study, we report predictors of CPAP adherence in older adults with aMCI who have increased odds of progressing to dementia, particularly due to Alzheimer's disease.

Methods: The data are from Memories 2, "Changing the Trajectory of Mild Cognitive Impairment with CPAP Treatment of Obstructive Sleep Apnea." Participants had moderate to severe OSA, were CPAP naïve, and received a telehealth CPAP adherence intervention. Linear and logistic regression models examined predictors.

Results: The 174 participants (mean age 67.08 years, 80 female, 38 Black persons) had a mean apnea-hypopnea index of 34.78, and 73.6% were adherent, defined as an average of ≥4 hours of CPAP use per night. Only 18 (47.4%) Black persons were CPAP adherent. In linear models, White race, moderate OSA, and participation in the tailored CPAP adherence intervention were significantly associated with higher CPAP use at 3 months. In logistic models, White persons had 9.94 times the odds of adhering to CPAP compared to Black persons. Age, sex, ethnicity, education, body mass index, nighttime sleep duration, daytime sleepiness, and cognitive status were not significant predictors.

Conclusions: Older patients with aMCI have high CPAP adherence, suggesting that age and cognitive impairment should not be a barrier to prescribing CPAP. Research is needed to improve adherence in Black patients, perhaps through culturally tailored interventions.

The National Institute on Aging sponsored a symposium at the Gerontological Society of America (GSA) annual meeting in Indianapolis, Indiana, to discuss recent discoveries related to senescent and inflammatory mechanisms in aging and disease. Consistent with the 2022 Biological Sciences GSA program led by Dr. Rozalyn Anderson, the symposium featured early-stage investigators and a leader in the field of geroscience research. Cell senescence and immune interactions coordinate homeostatic and protective programming throughout the life span. Dysfunctional communication in this exchange eventuates in inflammation-related compositional changes in aged tissues, including propagation of the senescence-associated secretory phenotype and accumulation of senescent and exhausted immune cells. Presentations in this symposium explored senescent and immune-related dysfunction in aging from diverse viewpoints and featured emerging cellular and molecular methods. A central takeaway from the event was that the use of new models and approaches, including single-cell -omics, novel mouse models, and 3D culture systems, is revealing dynamic properties and interactions of senescent and immune cell fates. This knowledge is critical for devising new therapeutic approaches with important translational relevance.