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

Background: Age is the greatest risk factor for lower urinary tract symptoms attributed to benign prostatic hyperplasia (LUTS/BPH). Although LUTS/BPH can be managed with pharmacotherapy, treatment failure has been putatively attributed to numerous pathological features of BPH (eg, prostatic fibrosis, inflammation). Mitochondrial dysfunction is a hallmark of aging; however, its impact on the pathological features of BPH remains unknown.

Methods: Publicly available gene array data were analyzed. Immunohistochemistry examined mitochondrial proteins in the human prostate. The effect of complex I inhibition (rotenone) on a prostatic cell line was examined using quantitative polymerase chain reaction, immunocytochemistry, and Seahorse assays. Oleic acid (OA) was tested as a bypass of complex I inhibition. Aged mice were treated with OA to examine its effects on urinary dysfunction. Voiding was assessed longitudinally, and a critical complex I protein measured.

Results: Mitochondrial function and fibrosis genes were altered in BPH. Essential mitochondrial proteins (ie, voltage-dependent anion channels 1 and 2, PTEN-induced kinase 1, and NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial [NDUFS3]) were significantly (p < .05) decreased in BPH. Complex I inhibition in cultured cells resulted in decreased respiration, altered NDUFS3 expression, increased collagen deposition, and gene expression. OA ameliorated these effects. OA-treated aged mice had significantly (p < .05) improved voiding function and higher prostatic NDUFS3 expression.

Conclusions: Complex I dysfunction is a potential contributor to fibrosis and lower urinary tract dysfunction in aged mice. OA partially bypasses complex I inhibition and therefore should be further investigated as a mitochondrial modulator for treatment of LUTS/BPH. Hypotheses generated in this investigation offer a heretofore unexplored cellular target of interest for the management of LUTS/BPH.

Background: Frailty is associated with urinary and fecal incontinence, which are common geriatric syndromes. This study aims to identify health factors associated with incontinence in prefrail or frail older adults living in the community.

Methods: This multicenter cross-sectional study included 225 older adults (75.0 ± 6.4 years) with prefrailty or frailty based on the 5-component Fried phenotype. Physical function was assessed using the Short Physical Performance Battery (SPPB). Physical activity, inactivity, and sleep were estimated using a wrist-worn accelerometer. Urinary or fecal incontinence was registered using the Barthel scale (urine and bowel items). Multivariable logistic regression analyses, with age as a covariate, were conducted to identify associations of incontinence.

Results: In our participants, 27% presented urinary or fecal incontinence with no sex differences (p = .266). Our results showed that age, daily medication count, and number of falls in the previous year independently predicted incontinence in frail and prefrail older adults (p < .05). Some Fried's criteria, including self-reported exhaustion, gait speed, and handgrip strength, were associated with the presence of incontinence (p < .05), but not Fried's classification. The SPPB total score and its isolated variables were significantly associated with the urinary and fecal incontinence (p < .05). However, none of the accelerometer outcomes showed significant associations with incontinence status.

Conclusions: According to this study, age, number of medications, and falls (but not sex) are linked to urinary and fecal incontinence in frail or prefrail older adults living in the community, recommending the assessment of physical function using the SPPB rather than estimating daily physical activity, inactivity, or sleep.

Background: Mounting evidence suggests that cognitive impairment is strongly associated with difficulties in performing activities of daily living (ADL disability). This study aims to estimate and project the trend in the number of older adults in China with ADL disability and cognitive impairment and the associated long-term care (LTC) costs in the next 20 years.

Methods: We used data from 37,942 adults aged ≥ 65 years from waves 2005-2018 of the Chinese Longitudinal Healthy Longevity Surveys (CLHLS). We used the Markov model to simulate the population of China and track the transition of Chinese older adults in the next 20 years between four disability-cognition states. We employed a two-part model to project direct and indirect LTC costs per capita.

Results: The proportion of disabled older adults without cognitive impairment (from 4.0% in 2022 to 4.3% in 2040) was projected to be slightly higher than that of those disabled and cognitively impaired (from 3.5% in 2022 to 4.1% in 2040). The indirect LTC cost was projected to increase from 316 billion yuan in 2022 to 4,399 billion yuan in 2040 for disabled older adults with cognitive impairment and from 197 billion yuan in 2022 to 1,697 billion yuan in 2040 for disabled older adults without cognitive impairment.

Conclusions: Policymakers could include the assessment of cognition in the LTC needs assessment and allocate more compensation to LTC insurance participants with cognitive impairment.

Macronutrient intake impacts physiology, behavior, and gene expression in a wide range of organisms. We used the response surface methodology to compare how life history traits, lifespan, and reproduction differ as a function of protein and carbohydrate intakes under choice and no-choice feeding regimens in the fruit fly, Drosophila melanogaster. We found that when offered a choice of nutritionally complementary foods mated female flies regulated toward a protein to carbohydrate ratio (P:C) that was associated with shortened lifespan and maximal egg production when compared to response surfaces derived from flies fed 1 of a range of fixed diets differing in P:C (no-choice regimen). This difference in lifespan between choice and no-choice feeding was not seen in males or virgin flies, reflecting the fact that increased protein intake is triggered by mating to support egg production. However, whereas in mated females a higher P:C intake was associated with greater egg production under both choice and no-choice feeding, contrary to expectations, choice-fed mated flies laid fewer eggs than no-choice flies on equivalent macronutrient intakes, perhaps reflecting that they had to ingest twice the volume of food to attain an equivalent intake of nutrients than no-choice flies on a diet of equivalent P:C ratio.

Background: Older adults are prone to live alone and feel lonely. The main objective of this study was to assess the associations of loneliness and living alone with cardiovascular disease (CVD) among community-dwelling older individuals in China.

Methods: We conducted a longitudinal analysis on 3 661 participants aged older than 65 years from the latest 2014 and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey. Cox proportional hazards models were used to assess the associations of loneliness and living alone with CVD risk, with adjustment for confounding factors.

Results: A total of 616 incident CVD cases were identified during follow-up. Participants who reported feeling lonely experienced a 28% increased risk of developing CVD after adjustment for sociodemographic characteristics, lifestyle factors, and baseline health status (adjusted hazard ratio [HR]: 1.28, 95% confidence interval [CI]: 1.01-1.62; ptrend = .046). In contrast, no significant association was observed between living alone and CVD risk. Subgroup analyses showed that among those individuals who lived alone, often feeling lonely doubled the risk of CVD compared to never being lonely (HR: 2.17, 95% CI: 1.20-3.93; ptrend = .007).

Conclusions: Loneliness was an independent risk factor for CVD among Chinese older adults. Our findings underscore the importance of addressing loneliness in the prevention of CVD among older individuals, especially those who live alone.

Background: Gait impairment leads to increased mobility decline and may have neurological contributions. This study explores how neurological biomarkers are related to gait in older adults.

Methods: We studied participants in the Cardiovascular Health Study, a population-based cohort of older Americans, who underwent a serum biomarker assessment from samples collected in 1996-1997 for neurofilament light chain (NfL), glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1, and total tau (n = 1 959, mean age = 78.0 years, 60.8% female). In a subsample (n = 380), cross-sectional associations with quantitative gait measures were explored. This subsample was assessed on a mat for gait speed, step length, double support time, step time, step length variability, and step time variability. Gait speed was also measured over a 15-ft walkway annually from 1996-1997 to 1998-1999 for longitudinal analyses. Linear regression models assessed cross-sectional associations of biomarkers with gait measures, whereas mixed effects models assessed longitudinal gait speed change from baseline to 1998-1999.

Results: Neurofilament light chain was significantly associated with annual gait speed decline (standardized β = -0.64 m/s, 95% CI: [-1.23, -0.06]) after adjustment for demographic and health factors. Among gait mat-assessed phenotypes, NfL was also cross-sectionally associated with gait speed (β = 0.001 m/s [0.0003, 0.002]) but not with other gait measures. None of the remaining biomarkers were significantly related to gait in either longitudinal or cross-sectional analyses.

Conclusions: Higher NfL levels were related to greater annual gait speed decline. Gait speed decline may be related to axonal degeneration. The clinical utility of NfL should be explored.

Background: Although the role of the vascular component in the pathophysiology of Parkinson's disease is widely accepted and retinal vascular abnormalities are commonly observed in Parkinson's disease patients, evidence connecting retinal vascular disorders with the risk of developing Parkinson's disease is limited. We aimed to investigate the association between retinal vascular occlusion (RVO) and the risk of developing Parkinson's disease in people over 60 years using a nationwide cohort.

Methods: From the 14-year South Korean National Health Insurance Service-Senior cohort, 11 210 incident RVO patients and 11 210 propensity scores, risk-matched controls were included. The incidence of Parkinson's disease was estimated with a Poisson regression. A Cox proportional hazards regression model was used to investigate the associations between RVO and the risk of Parkinson's disease.

Results: The incidence of Parkinson's disease was 664.4 cases per 100 000 person-years (95% confidence interval [CI], 599.7-736.0) in the RVO cohort. Individuals with RVO had an increased incidence of Parkinson's disease (hazard ratio [HR], 1.28; 95% CI: 1.10-1.49). Increased PD risk was predominantly observed in retinal artery occlusion patients (HR, 1.53; 95% CI: 1.11-2.12), male patients (HR, 1.67; 95% CI: 1.29-2.17), and 5 years after diagnosis (HR, 1.46; 95% CI: 1.10-1.93).

Conclusions: Our findings suggest that a common pathophysiological pathway, such as vasculature changes, may exist between RVO and Parkinson's disease. RVO may be one of the risk factors associated with future development of Parkinson's disease. The nature of this association warrants further investigation.

Background: Circulating levels of n-3 polyunsaturated fatty acids (PUFAs) have been associated with frailty among Koreans (a population with a high intake of fish), but whether this association exists in Western populations with low fish intake is unknown. The present study examined the hypothesis that the prevalence of frailty was inversely associated with plasma levels of n-3 PUFAs, with the intake of oily fish, and with fish oil supplementation in older adults in the United Kingdom.

Methods: UK Biobank including 79 330 adults aged ≥65 years with dietary data, and 18 802 participants with plasma fatty acid data were used. Frailty was defined using the Cardiovascular Health Study index, plasma levels of n-3 PUFAs were measured by nuclear magnetic resonance, and intake of oily fish and/or fish oil supplements was collected via food frequency questionnaire.

Results: Frailty prevalence was inversely associated with n-3 PUFA levels [odds ratios (OR) per SD: 0.86, 95% confidence interval (CI) 0.79-0.94; p < .001], with oily fish intake (never vs ≥2 servings per week; OR 0.59, 95% CI 0.52-0.68, p < .001), and with the use of fish oil supplements (OR 0.72; 95% CI 0.66-0.78; p < .001) after adjusting for confounding factors. All 3 exposures were also associated with each frailty criterion, particularly low physical activity and walking pace.

Conclusions: Inverse associations between plasma n-3 PUFA levels and measures of frailty suggest that higher intakes of oily fish or the use of fish oil supplements may help prevent frailty in older adults in the United Kingdom.