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

Background: The relationship between pain characteristics and chronic disease development in aging populations remains poorly understood. This study explored associations between early pain exposure and incident chronic diseases in older adults through epidemiological and genetic analyses.

Methods: Using data from China Health and Retirement Longitudinal Study (CHARLS) and English Longitudinal Study of Ageing (ELSA), participants were classified by pain trajectories across consecutive surveys: "now stronger/more sites/more frequent, previously stronger/more sites/more frequent, persistently pain-free, persistently strong/multiple/frequent." Cohorts were followed for incident chronic conditions through 2018 (CHARLS) and 2015 (ELSA). Mendelian randomization (MR) examined causal relationships between multisite chronic pain and disease outcomes.

Results: Early pain trajectory changes were significantly associated with increased incidence of multiple chronic diseases. Participants with "persistently strong pain" or "now stronger pain" demonstrated 37%-267% increased disease risks, particularly for chronic lung disease (HR 2.11, 95% CI: 1.52-2.94) and memory-related diseases (HR 3.67, 95% CI: 1.15-11.71); those with "previously stronger pain" remained associated with 24%-124% elevated risks, especially for liver disease (HR 2.24, 95% CI: 1.56-3.22). "Persistently multiple sites" or "now more sites" trajectories were associated with 58%-275% higher risks; "previously more sites" was associated with 39%-203% elevated risks. "Persistently frequent" pain was associated with 62%-131% increased risks. MR confirmed genetic associations between multisite chronic pain and 30 chronic diseases.

Conclusions: The burden of chronic pain in older adults has been underestimated by overlooking its potential association with elevated risks across multiple chronic diseases. Monitoring pain intensity, sites, and frequency should be integrated into geriatric evaluation to promote healthy aging.

Compounds promoting anabolic effects on muscle and bone may offer an ideal treatment for osteosarcopenia while potentially impacting healthspan and lifespan. We previously demonstrated the anabolic effects of picolinic acid (PIC), a tryptophan metabolite, on bone both in vitro and in vivo. However, its effects on muscle and potential additional effects on lifespan and healthspan are not yet fully understood. This study aimed to investigate PIC's effects on muscle cells in vitro and its impact on mobility and lifespan in an animal model. Murine C2C12 and human myoblasts were treated with PIC (1, 50, and 100 µM) or vehicle for 5 days. Myogenic regulatory factors (MRFs) were evaluated, and the fusion index and myotubules' length were calculated at timed intervals (day 1, 3, and 5). In vivo, Caenorhabditis elegans were treated with increasing doses of PIC, and their lifespan and rate of movement (thrashing) were evaluated at timed intervals. PIC-treated myoblasts showed a higher and earlier expression of MRFs. On day 3, PIC-treated myotubes were significantly more fused and longer when treated with PIC than vehicle-treated controls. C. elegans treated with 1 mM of PIC showed a significantly longer lifespan. In addition, the mobility of PIC-treated C. elegans was significantly increased at all timed points. In conclusion, this study demonstrates that, besides its anabolic effect on bone, PIC has an anabolic effect on muscle, which is also associated with a longer lifespan in PIC-treated C. elegans. This evidence opens up promising avenues for further exploration of PIC as a novel therapy for osteosarcopenia with additional effects on healthspan and lifespan.

Background: Sleep disturbances and cardiovascular disease are common and often co-occur in middle-aged and older adults, but less is known about associations of sleep with cardiorespiratory fitness (CRF) and energy efficiency in these populations. We examined cross-sectional associations of accelerometer-derived sleep metrics with CRF, walking energetics, and resting metabolic rate (RMR), and explored whether associations were moderated by age, sex, and race.

Methods: We studied 263 participants from the Baltimore Longitudinal Study of Aging (mean age 72.7 ± 10.1 years, 53.6% women). Predictors included total sleep time (TST), sleep efficiency (SE), sleep onset latency, wake after sleep onset, and average wake bout length (WBL). Outcomes included measures of CRF (ie, maximal oxygen consumption [VO2peak]) and energetic efficiency (ie, energetic cost of walking and RMR).

Results: After adjusting for demographics, comorbidities, and self-reported physical activity, longer WBL was associated with lower VO2peak (B= -1.01 ml/kg/min, P < .01) and higher RMR (B = 43.25 kcal, P < .05), lower SE was associated with lower VO2peak (B = 1.07 ml/kg/min, P < .01), and shorter TST was associated with lower VO2peak (B = 0.33 ml/kg/min, P < .05). Higher SE was associated with lower RMR among middle-aged adults but not older adults (interaction P-value < 0.05).

Conclusion: Shorter TST, longer WBL, and lower SE are associated with poorer CRF and energetic efficiency among middle-aged and older adults. Longitudinal studies are needed to understand the temporality of these associations and potential targets for interventions in these populations.

Background: Peak oxygen consumption during exercise (VO2peak), is a direct measure of cardiorespiratory fitness (CF), a key indicator of physical function and overall health. However, the molecular changes that underpin VO2peak variation are not clear. Our objective is to understand the microRNA (miRNA) signatures that relate to VO2peak variation, which could provide insights to novel mechanisms that contribute to low VO2peak.

Methods: We used small RNA sequencing to analyze baseline, cross-sectional serum samples from 72 participants (70- to 91-year old). We analyzed samples from individuals with low or high VO2peak (N = 18/group) as well as samples from 36 randomly selected participants spanning the entire spectrum of VO2peak. We used LIMMA analysis package for regression analysis and to identify differentially expressed miRNAs.

Results: We identified 1055 miRNAs expressed in all serum samples. Expression of 65 miRNAs differed between participants with low and high VO2peak (P < .05). After P-value adjustment, expression of 5 miRNAs (miR-1301-3p, -431-5p, -501-5p, -519a-3p, and -18a-3p) remained significantly different (FDR = 0.05). The Area Under the Curve for the five miRNAs ranged from 0.77 to 0.84. The optimal sensitivity and specificity ranged from 70% to 80% and 80% to 90%, respectively. After adjustment for age and sex covariates, 46 miRNAs significantly correlated with VO2peak (P < .05) and miR-519a-3p remained significant based on adjusted P-values.

Conclusions: We identified a miRNA signature of VO2peak in older individuals that might provide insights to novel mechanisms that drive low VO2peak. Future studies will validate the findings in a larger, longitudinal study cohort.

With parental age rising around the globe, an increased understanding of the impact on health and longevity is needed. Here, we report how the continuous selection of the last progeny during the Caenorhabditis elegans reproductive span results in a diminishment of multiple age-related health measures. After more than 50 generations of late selection, progeny displayed diminished resistance to acute oxidative stress, disrupted partitioning of stored lipids, reduced movement capacity, and an overall shortening of lifespan (36.84% reduction). In contrast, starvation resistance was improved and late selection had negligible effects on developmental timing and total reproductive output that suggests a reduction in lifespan health to preserve reproductive capacity. The phenotypes of late selection are reminiscent of animals with activation of the cytoprotective transcription factor SKN-1 that may facilitate transcriptional remodeling following late reproductive selection. These findings suggest the existence of a homeostatic mechanism for bookmarking the temporal boundaries of the parental reproductive span that reshapes the way we think about parental age influencing offspring fitness.

Background: Current understanding of the last year of life with dementia is disproportionately informed by studies conducted in western contexts, primarily within long-term care settings. This study examines the last year of life experience for community-dwelling older adults and their caregivers in an Asian setting.

Methods: Using prospective longitudinal cohort data from 125 family caregivers to older adults who have died during the study, we estimate separate random effects regression models to identify factors associated with hospital admissions, medical interventions, care experience, and informal caregiving hours. We also estimate costs associated with informal caregiving hours.

Results: Nearly half (48%) of older adults experienced an inpatient admission, and nearly all (92%) experienced a potentially burdensome intervention. Urinary tract infections were the strongest predictor of hospital admissions (adjusted odds ratio [AOR] = 10.42, p = .00) and medical interventions (AOR = 9.61, p = .02). Pneumonia (AOR = 8.40, p = .05) and febrile episodes (AOR = 3.94, p = .03) were associated with increased odds of intervention, whereas caregivers who prioritized comfort care only were associated with reduced interventions (AOR = 0.28, p = .04) and increased admissions (AOR = 3.20, p = .04). Family caregivers provided 42 hours of care per week on average, and 30% gave up their employment to care for the older adult during the older adult's final year.

Conclusions: Community-dwelling older adults in Singapore experienced similar clinical problems and potentially more burdensome interventions, including feeding tubes and physical restraints, than described previously in other contexts, highlighting the need for a palliative approach not apparent in the frequent acute care utilization, interventions, and caregiving burden observed.