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

Background: Unclean cooking fuels (ie, polluting fuels including kerosene/paraffin, and solid fuels) are a major contributor to diseases and mortality, specifically in low- and middle-income countries.

Methods: This review aimed to identify potential mechanisms, public health implications, and future directions of unclean cooking fuel use and health outcomes in older adults.

Results: There is an expanding body of literature to demonstrate associations between unclean cooking fuel use and multiple mental and physical health outcomes in older adults. Two key mechanisms likely driving such associations include inflammation and oxidative stress.

Conclusions: Considering that inflammation and oxidative stress have been implicated in multiple other health conditions (eg, arthritis and osteoporosis) in addition to those investigated to date on this topic it would be prudent to continue investigation of unclean cooking fuel use and with yet to be studied health outcomes. Moreover, future research is indeed now required to identify pathways to eliminating unclean cooking fuel globally to better the health of an aging global population and to support the implementation of Sustainable Development Goal 7.

Plasma Alzheimer's disease-related pathological biomarkers' role in Parkinson's disease (PD) remains unknown. We aimed to determine whether plasma Alzheimer's disease-related biomarkers can predict PD progression. A total of 184 PD patients and 86 healthy controls were included and followed up for 5 years. Plasma phosphorylated tau181 (p-tau181), Aβ40, and Aβ42 were measured at baseline and the 1- and 2-year follow-ups using the Quanterix-single-molecule array. Global cognitive function and motor symptoms were assessed using the Montreal Cognitive Assessment and Unified Parkinson's Disease Rating Scale part III. Genetic analyses were conducted to identify APOE and MAPT genotypes. Plasma p-tau181 levels were higher in PD than healthy controls. APOE-ε4 carriers had lower plasma Aβ42 levels and Aβ42/Aβ40 ratio. The linear mixed-effects models showed that Montreal Cognitive Assessment scores were associated with plasma p-tau181/Aβ42 ratio (β -1.719 [-3.398 to -0.040], p = .045). Higher baseline plasma p-tau181 correlated with faster cognitive decline and motor symptoms deterioration in total patients (β -0.170 [-0.322 to -0.018], p = .029; β 0.329 [0.032 to 0.626], p = .030) and APOE-ε4 carriers (β -0.318 [-0.602 to -0.034], p = .030; β 0.632 [0.017 to 1.246], p = .046), but not in the noncarriers. Higher baseline plasma Aβ40 correlated with faster cognitive decline in total patients (β -0.007 [-0.015 to -0.0001], p = .047) and faster motor symptoms deterioration in total patients (β 0.026 [0.010 to 0.041], p = .001) and APOE-ε4 carriers (β 0.044 [-0.026 to 0.049], p = .020), but not in the noncarriers. The plasma p-tau181/Aβ2 ratio monitors the cognitive status of PD. Higher baseline plasma p-tau181 and Aβ40 predict faster cognitive decline and motor symptoms deterioration in PD, especially in APOE-ε4 carriers.

Advancing age and many disease states are associated with declines in nicotinamide adenine dinucleotide (NAD+) levels. Preclinical studies suggest that boosting NAD+ abundance with precursor compounds, such as nicotinamide riboside or nicotinamide mononucleotide, has profound effects on physiological function in models of aging and disease. Translation of these compounds for oral supplementation in humans has been increasingly studied within the last 10 years; however, the clinical evidence that raising NAD+ concentrations can improve physiological function is unclear. The goal of this review was to synthesize the published literature on the effects of chronic oral supplementation with NAD+ precursors on healthy aging and age-related chronic diseases. We identified nicotinamide riboside, nicotinamide riboside co-administered with pterostilbene, and nicotinamide mononucleotide as the most common candidates in investigations of NAD+-boosting compounds for improving physiological function in humans. Studies have been performed in generally healthy midlife and older adults, adults with cardiometabolic disease risk factors such as overweight and obesity, and numerous patient populations. Supplementation with these compounds is safe, tolerable, and can increase the abundance of NAD+ and related metabolites in multiple tissues. Dosing regimens and study durations vary greatly across interventions, and small sample sizes limit data interpretation of physiological outcomes. Limitations are identified and future research directions are suggested to further our understanding of the potential efficacy of NAD+-boosting compounds for improving physiological function and extending human health span.

Background: The influence of overall air pollution on dementia risk and the potential effect modification by other risk factors remain to be clarified.

Methods: We included 459 844 UK residents who were free of dementia and had data on the exposure to particulate matter (PM)2.5, PM2.5-10, PM10, NO2, and NOx during baseline recruitment. The combined exposure to various PMs and NOx was estimated by using an air pollution score. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incident dementia were estimated by multivariable Cox models.

Results: During a median 11.7 years follow-up, 5 905 incident cases of all-cause dementia were identified. With the exception of PM2.5-10, all other air pollutants were separately associated with a higher risk of all-cause dementia (all p-trend < .001) with generally similar associations for dementia subtypes. An increasing air pollution score was associated with higher risks of all-cause as well as individual dementia outcomes, with adjusted HRs (95% CI) of 1.27 (1.18, 1.37) for all-cause dementia, 1.27 (1.14, 1.43) for Alzheimer's disease, and 1.35 (1.16, 1.57) for vascular dementia when comparing the highest with the lowest quartile of the score (all p-trend < .001). These associations of air pollution score with dementia and its subtypes were observed among never and former smokers but not among current smokers (all p-interaction 
< .030).

Conclusion: Air pollution was associated with a higher risk of dementia among nonsmokers but not current smokers. Additional studies are required to confirm our findings and to explore the potential mechanisms underlying the possible effect modification by smoking status.

Background: Long-term exposure to PM2.5 is related to poor lung function and cognitive impairment, but less is known about the pathway involved in this association. We aimed to explore whether the effect of PM2.5 on cognitive function was mediated by lung function.

Methods: A total of 7 915 adults older than 45 years old were derived from the China Health and Retirement Longitudinal Study (CHARLS) collected in 2011 and 2015. PM2.5 exposure was estimated using a geographically weighted regression model. Lung function was measured by peak expiratory flow (PEF). Cognitive function was evaluated through a structured questionnaire with 4 dimensions: episodic memory, attention, orientation, and visuoconstruction. Under the counterfactual framework, causal mediation analysis was applied to examine direct and indirect associations.

Results: An interquartile range (IQR) increase in PM2.5 change was significantly related to an 8.480 (95% confidence interval [CI]: 3.116, 13.845) decrease in PEF change and a 0.301 (95% CI: 0.100, 0.575) decrease in global cognitive score change. The direct and indirect effects of PM2.5 exposure on global cognitive performance were -0.279 (95% CI: -0.551, -0.060) and -0.023 (95% CI: -0.041, -0.010), respectively. The proportion of the indirect effect was 7.48% (p = .010). The same significant association appeared in only 2 dimensions, episodic memory and attention, which were both mediated by PEF.

Conclusions: Lung function played a partially mediating role in the association between long-term PM2.5 exposure and cognition. More clean air actions should be undertaken to improve lung function and cognitive function in older adults.

Background: Although studies have demonstrated associations between sleep quality (SQ) and grip strength (GS) in older adults, the direction and underlying mechanisms of this relationship are yet to be better delineated. We aimed to longitudinally investigate the bidirectional association between SQ and GS and the mediating role of depression in this association.

Methods: Based on 2 nationally representative samples with people aged ≥50 years from the China Health and Retirement Longitudinal Study (CHARLS; 4 200 participants) and English Longitudinal Study of Ageing (ELSA; 5 922 participants), cross-lagged panel models were employed to examine the potential bidirectional relationships between objectively measured GS and self-reported SQ.

Results: We observed a GS-SQ bidirectional association dominated by GS. After adjusting for potential confounders, a higher GS at T1 predicted better SQ at T2 (ELSA: β = 0.075; CHARLS: β = 0.104, p < .001) and vice versa (ELSA: β = 0.034; CHARLS: β = 0.030, p < .01). Moreover, depression partially mediated the impact of GS on subsequent SQ (ELSA, indirect effect: 0.0057, 95% confidence interval [CI]: 0.0035-0.0084; CHARLS, indirect effect: 0.0086, 95% CI: 0.0051, 0.0131), but not vice versa.

Conclusions: The results regarding data from both cohorts consistently supported a bidirectional association between GS and SQ and the mediating role of depression in the dominant pathway of this bidirectional relationship. Older adults with a low GS should be made aware of a potentially vicious cycle related to depression that can affect their sleep. Regular screening for depression may help to break this cycle.

The standard evolutionary theory of aging predicts a negative relationship (trade-off) between fecundity and longevity. However, in principle, the fecundity-longevity relationship can become positive in populations in which individuals have unequal resources. Positive fecundity-longevity relationships also occur in queens of eusocial insects such as ants and bees. Developmental diet is likely to be central to determining trade-offs as it affects key fitness traits, but its exact role remains uncertain. For example, in Drosophila melanogaster, changes in adult diet can affect fecundity, longevity, and gene expression throughout life, but it is unknown how changes in developmental (larval) diet affect fecundity-longevity relationships and gene expression in adults. Using D. melanogaster, we tested the hypothesis that varying developmental diets alters the directionality of fecundity-longevity relationships in adults, and characterized associated gene expression changes. We reared larvae on low (20%), medium (100%), and high (120%) yeast diets, and transferred adult females to a common diet. We measured fecundity and longevity of individual adult females and profiled gene expression changes with age. Adult females raised on different larval diets exhibited fecundity-longevity relationships that varied from significantly positive to significantly negative, despite minimal differences in mean lifetime fertility or longevity. Treatments also differed in age-related gene expression, including for aging-related genes. Hence, the sign of fecundity-longevity relationships in adult insects can be altered and even reversed by changes in larval diet quality. By extension, larval diet differences may represent a key mechanistic factor underpinning positive fecundity-longevity relationships observed in species such as eusocial insects.

Background: Co-occurring insomnia and daytime sleepiness has an undetermined clinical significance in older adults. We aimed to investigate the relationship between various combinations of insomnia and daytime sleepiness with mortality risk in community-dwelling older adults. The moderation effect of sex was also assessed.

Methods: We conducted this follow-up study including community-dwelling adults aged ≥65 in Yilan City, Taiwan. Daytime sleepiness was defined as scoring ≥11 on the Epworth Sleepiness Scale. Insomnia was defined as scores ≥5 on the Athens Insomnia Scale-5. Four phenotypes were defined based on the presence of insomnia or daytime sleepiness. The 9-year mortality risks for various phenotypic combinations were estimated using Cox regression analysis. Sex-specific risks were examined using an interaction term.

Results: In total, 2 702 older adults participated in the study, and 59.1% were women. The total 9-year mortality rate was 27.5%. After adjusting for all covariates, compared with those without insomnia or daytime sleepiness, the phenotype of co-occurring insomnia with daytime sleepiness predicted higher mortality risk (hazard ratio [HR]: 1.76, confidence interval [CI]: 1.20-2.58). In contrast, insomnia and daytime sleepiness alone did not correlate with higher mortality. The interaction between sex with co-occurring insomnia and daytime sleepiness was significant (p = .01). When stratifying by sex, the association between co-occurring insomnia and daytime sleepiness with higher mortality risk was male-specific (HR: 3.07, CI: 1.87-5.04).

Conclusions: Concurrence of insomnia and daytime sleepiness indicates a toxic phenotypic combination in older adults, particularly in men. Precise public health and preventive medicine can be implemented through geriatric sleep medicine.

Human society is aging, and the percentage of the population of older adults is increasing at an unprecedented rate. It is increasingly appreciated that social behaviors change with aging. One such example is the possible aging-related reduction in dominance status. This change has been thought to underlie older adults' peculiar vulnerability to fraud, which has become a major challenge in the present aging society. However, whether this change is an inherent physiological process, and, if so, its underlying microscopic physiological mechanism, is not known. This study used groups of mice in a design that minimized effects that could confound any inherent process of dominance and verified that social dominance does inherently reduce with aging. This study further identified an aging-related microscopic functional alteration, that is, a reduction in the activity of glutamatergic pyramidal neurons in the prelimbic medial prefrontal cortex; and established that this reduction in neuronal activity serves as an intrinsic physiological mechanism underlying the macroscopic aging-related reduction in dominance. This study, by exploiting modern neurobiological techniques, sheds light on our understanding of human social behaviors during aging and may help develop strategies to counter related social challenges among the older adults population.

Background: Racial and ethnic disparities in coronavirus disease 2019 (COVID-19) risk are well-documented; however, few studies in older adults have examined multiple factors related to COVID-19 exposure, concerns, and behaviors or conducted race- and ethnicity-stratified analyses. The Women's Health Initiative (WHI) provides a unique opportunity to address those gaps.

Methods: We conducted a secondary analysis of WHI data from a supplemental survey of 48 492 older adults (mean age 84 years). In multivariable-adjusted modified Poisson regression analyses, we examined predisposing factors and COVID-19 exposure risk, concerns, and behaviors. We hypothesized that women from minoritized racial or ethnic groups, compared to non-Hispanic White women, would be more likely to report: exposure to COVID-19, a family or friend dying from COVID-19, difficulty getting routine medical care or deciding to forego care to avoid COVID-19 exposure, and having concerns about the COVID-19 pandemic.

Results: Asian women and non-Hispanic Black/African American women had a higher risk of being somewhat/very concerned about risk of getting COVID-19 compared to non-Hispanic White women and each was significantly more likely than non-Hispanic White women to report forgoing medical care to avoid COVID-19 exposure. However, Asian women were 35% less likely than non-Hispanic White women to report difficulty getting routine medical care since March 2020 (adjusted relative risk 0.65; 95% confidence interval 0.57, 0.75).

Conclusions: We documented COVID-related racial and ethnic disparities in COVID-19 exposure risk, concerns, and care-related behaviors that disfavored minoritized racial and ethnic groups, particularly non-Hispanic Black/African American women.