Gerontology最新文献

Introduction: While several antidepressants have been identified as potential geroprotectors, the effect and mechanism of sertraline on healthspan remain to be elucidated. Here, we explored the role of sertraline in the lifespan and healthspan of Caenorhabditis elegans.

Methods: The optimal effect concentration of sertraline was first screened in wild-type N2 worms under heat stress conditions. Then, we examined the effects of sertraline on lifespan, reproduction, lipofuscin accumulation, mobility, and stress resistance. Finally, the expression of serotonin signaling and aging-related genes was investigated to explore the underlying mechanism, and the lifespan assays were performed in ser-7 RNAi strain, daf-2, daf-16, and aak-2 mutants.

Results: Sertraline extended the lifespan in C. elegans with concomitant extension of healthspan as indicated by increasing mobility and reducing fertility and lipofuscin accumulation, as well as enhanced resistance to different abiotic stresses. Mechanistically, ser-7 orchestrated sertraline-induced longevity via the regulation of insulin and AMPK pathways, and sertraline-induced lifespan extension in nematodes was abolished in ser-7 RNAi strain, daf-2, daf-16, and aak-2 mutants.

Conclusion: Sertraline promotes health and longevity in C. elegans through ser-7-insulin/AMPK pathways.

Introduction: Despite growing calls to tackle aging-related cardiovascular disease (CVD), the role of detecting early diastolic dysfunction such as those observed in aging, prior to clinical disease, is of unclear clinical benefit.

Methods: Myocardial function determined by echocardiography was examined in association with incident cardiovascular outcomes or all-cause death by Cox proportional hazards model. Sex-based differences in outcomes were included.

Results: A total of 956 participants (mean age 63 ± 12.9 years, n = 424 males [44%]) were categorized based on mitral peak early-to-late diastolic filling velocity (E/A) ratios: E/A <0.8 (28%), E/A 0.8-1.2 (39%), E/A (29%), E/A >2.0 (4%). Incidence rate (IR) for non-fatal cardiovascular outcomes was 2.83 per 100 person-years (95% CI: 2.24-3.56) and 0.45 per 100 person-years (95% CI: 0.26-0.80) for all-cause death. Event-free survival from non-fatal cardiovascular outcomes was significantly different among E/A categories (log-rank p = 0.0269). E/A <0.8 (HR 1.80, 95% CI: 1.031, 3.14, p = 0.039) was associated with non-fatal cardiovascular outcomes. Among men, IR for cardiovascular outcomes was 3.56 per 100 person-years (95% CI: 2.62-4.84) and 0.75 per 100 person-years (95% CI: 0.39-1.44) for all-cause death. Among women, IR for cardiovascular outcomes was 2.22 per 100 person-years (95% CI: 1.56-3.16) and 0.21 per 100 person-years (95% CI: 0.067-0.64) for all-cause death. For E/A <0.8 category, women had significantly higher risks of non-fatal cardiovascular outcomes, compared to E/A 0.8-1.2 category (HR 2.49, 95% CI: 1.18, 5.23, p = 0.017).

Conclusion: Myocardial aging was an independent predictor of cardiovascular outcomes in community-dwelling older adults prior to clinical CVD. Impaired myocardial relaxation was prevalent in both sexes but associated with worse outcomes in women, suggestive of sex differences in age-related biology.

Introduction: Reactivity to daily stressors may change as a function of stressor type and age. However, prior research often excludes older adults or compares them to younger age groups (e.g., younger and middle-aged adults). Recognizing older adults as a heterogeneous population with shifting motivations, this study focused on individuals aged ≥65 years and tested age differences in associations between different types of daily stressors, affect, and physical symptoms.

Methods: A total of 108 older adults aged 65-92 years (M = 73.11, SD = 5.92; 58% women) completed daily dairy questionnaires on daily stressors, positive and negative affect, and physical symptoms for 14 consecutive days. Multilevel models were employed, adjusting for sex, age, education, living situation, and day-in-study.

Results: Findings revealed age-dependent variations in the associations between daily stressors and affect and physical symptoms. Specifically, external stressors (e.g., finance and traffic stressors) and health stressors were more strongly associated with daily affective states and with overall physical symptoms (respectively) among older age adults. Age did not moderate associations between social stressors and affect or physical symptoms.

Conclusion: These findings underscore the heterogeneous nature of older adults' responses to daily stressors based on stressor type and age. Specifically, the oldest-old might benefit from personalized support for dealing with challenges such as health and financial stressors.

Introduction: Older adults are usually perceived as warmer but less competent than younger adults. This study examined how these stereotypes are related to domain-specific attributes and how individuals' values may moderate the association.

Methods: We recruited 560 Chinese participants (mean age [SD]: 23.14 ± 7.08 years old, ranging from 18 to 60 years old) and 479 American participants (mean age [SD]: 31.37 ± 7.19 years old, ranging from 18 to 57 years old). Participants rated perceived warmth and competence of older adults based on vignettes with varying descriptions of specific domains (i.e., three relational domains: number of friends, family relationship quality, and engagement in neighbourhood activities; and three individualistic domains: income, depression, and memory) and personal attributes (i.e., gender, age, and independence).

Results: Firstly, the results showed that relational domains predict warmth, whereas individualistic domains predict competence in both samples from China and the USA. Secondly, in both samples, people with higher communal values attributed more relevance to relational domains on judgement of warmth. Lastly, only in the US sample did people with higher agentic values attribute more relevance to individualistic domains on judgement of competence.

Discussion/conclusion: The study revealed that personal values, when determined relatively, contribute to stereotypes of older adults in the two independent samples.

Introduction: Educational differences in cognitive performance among older adults are well documented. Studies that explore this association typically estimate a single average effect of education on cognitive performance. We argue that the processes that contribute to the association between education and cognitive performance are unlikely to have equal effects at all levels of cognitive performance. In this study, we employ an analytical approach that enables us to go beyond averages to examine the association between education and five measures of global and domain-specific cognitive performance across the outcome distributions.

Methods: This cross-sectional study included 1,780 older adults aged 58-68 years from the Longitudinal Aging Study Amsterdam. Conditional quantile regression was used to examine variation across the outcome distribution. Cognitive outcomes included Mini-Mental State Examination (MMSE) score, crystallized intelligence, information processing speed, episodic memory, and a composite score of global cognitive performance.

Results: The results showed that the associations between education and different cognitive measures varied across the outcome distributions. Specifically, we found that education had a stronger association with crystallized intelligence, MMSE, and a composite cognitive performance measure in the lower tail of performance distributions. The associations between education and information processing speed and episodic memory were uniform across the outcome distributions.

Conclusion: Larger associations between education and some domains of cognitive performance in the lower tail of the performance distributions imply that inequalities are primarily generated among individuals with lower performance rather than among average and high performers. Additionally, the varying associations across some of the outcome distributions indicate that estimating a single average effect through standard regression methods may overlook variations in cognitive performance between educational groups. Future studies should consider heterogeneity across the outcome distribution.

Introduction: Loneliness, social inactivity, and social isolation are intertwined concepts. When assessed separately, they indicate poor well-being, adverse health effects, and increased mortality. Studies exploring overlapping and comparing the prognosis of these concepts are scarce. We investigated (1) overlapping of concepts of loneliness, social inactivity, and social isolation, (2) characteristics of groups: group 0 (not lonely, socially inactive, or socially isolated), group 1 (lonely), group 2 (not lonely but socially inactive and/or socially isolated), and (3) the health-related quality of life (HRQoL), psychological well-being (PWB), and 3.6-year mortality of these groups.

Methods: The home-dwelling older adults (n = 989; 75 y+) of the Helsinki Aging Study in 2019-2022 completing all required questionnaires were assessed. Group 0 included 494, group 1 included 280, and group 2 included 215 participants. Variables studied were demographics, diagnoses, mobility, physical functioning (Barthel index), and cognition (Mini-Mental State Examination). Outcomes were HRQoL (15D) and PWB. Mortality was retrieved from central registers.

Results: Half of the sample was lonely, socially inactive, or socially isolated, but only 2% were simultaneously lonely, socially inactive, and socially isolated. Of lonely participants, 38% were also socially inactive and/or socially isolated. The lonely participants were significantly more often widowed or lived alone and had the lowest HRQoL and poorest PWB compared with the other groups. After adjustments (age, sex, Charlson Comorbidity Index), mortality did not statistically differ between the groups.

Conclusion: Loneliness is an independent determinant of poor HRQoL and PWB, and it should be considered separately from social inactivity and social isolation.

Introduction: Hypertension can accelerate and aggravate the process of arterial ageing and calcification. However, the mechanism behind has yet to be well elucidated.

Methods: Here, we monitored the dynamic changes of fibronectin (FN)/α5 integrin, bone morphogenetic protein 2/matrix Gla protein (BMP2/MGP), and Runx2 in the aorta of spontaneously hypertensive rats (SHRs) and thoracic aortic vascular smooth muscle cells (VSMCs), also the phenotypic transformation of VSMCs during the process of arterial ageing and calcification. Further, study on arterial ageing and calcification through antagonist experiments at the molecular level was explored.

Results: We found extracellular FN and its α5 integrin receptor expressions were positively associated with arterial ageing and calcification in SHR during ageing, as well in VSMCs from SHR in vitro. Integrin receptor inhibitor of GRGDSP would delay this arterial ageing and calcification process. Moreover, the elevated FN and α5 integrin receptor expression evoked the disequilibrium of BMP2/MGP, where the expression of BMP2, a potent osteogenic inducer, increased while MGP, a calcification inhibitor, decreased. Furthermore, it was followed by the upregulation of Runx2 and the phenotypic transformation of VSMCs from the contractile phenotype into the osteoblast-like cells. Notably, BMP2 antagonist of rmNoggin was sufficient to ameliorate the ageing and calcification process of VSMCs and exogenous BMP2-adding accelerate and aggregate the process.

Conclusion: Our study revealed that hypertension-associated arterial ageing and calcification might be a consequence that hypertension up-regulated FN and its high binding affinity integrin α5 receptor in the aortic wall, which in turn aggravated the imbalance of BMP2/MGP, promoted the transcription of Runx2, and induced the phenotypic transformation of VSMCs from the contractile phenotype into the osteoblast-like cells. Our study would provide insights into hypertension-associated arterial ageing and calcification and shed new light on the control of arterial calcification, especially for those with hypertension.

Introduction: Sarcopenia, heart failure (HF), and chronic kidney disease (CKD) are common among the older people. Our objective was to evaluate the frequency of sarcopenia, among community-dwelling older adults with HF, possible causative factors, and the additive factor of CKD.

Methods: A cross-sectional analysis of 1,420 older people living in the community was carried out. Participants (aged 75 years and more) came from a European multicenter prospective cohort (SCOPE study). Global geriatric assessment including short physical performance battery, handgrip strength test, and bioelectrical impedance analysis was performed. Previous known HF was defined as physician-diagnosed HF registered in the patient's medical record or the use of HF-related medications, regardless of left ventricular ejection fraction (LVEF). Sarcopenia was defined by the updated criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Estimated glomerular filtration rate was calculated using Berlin Initiative Study (BIS) to define the stages of CKD. Two-year mortality was also collected.

Results: A total of 226 (15.9%) participants had a prior chronic HF diagnosis, with a median age of 80.0 (5.0), and 123 (54.4%) were women. Using EWGSOP2 definition, 11.5% HF and 10.7% in non-HF participants met diagnostic criteria for sarcopenia. In multivariate analyses, only a lower body mass index (BMI) (odds ratios [OR], 0.82; 95% confidence interval [CI], 0.73-0.93) and lower short physical performance battery score (OR, 0.81; 95% CI, 0.69-0.96) were associated with sarcopenia. Patients with HF and sarcopenia have a similar all-cause mortality risk but higher 2-year cardiovascular mortality risk (p = 0.047).

Discussion/conclusion: One out of ten community-dwelling older adults with concurrent clinical stable chronic HF, without considering LVEF, have sarcopenia. Lower BMI and poor physical performance are associated with sarcopenia in this population, but not CKD.