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

Age-related hearing loss, or Presbycusis, is the most frequent sensory deficiency in older adults and is associated with comorbidities such as falls, cognitive decline, and frailty. Frailty is related to poor health outcomes in old age. Recent research suggested that age-related hearing loss may be a potentially modifiable risk factor for frailty, although inconclusive. The use of animal models to study the correlation between age-related hearing loss and frailty is important to test future interventions to be translated into clinical practice. The aim of this study was to determine if there is an association between age-related hearing loss and frailty in experimental animals based on the human frailty phenotype. This research studied male and female C57Bl/6J mice at different ages (6, 14, and 22 months). Auditory steady-state response threshold shifts were measured at different frequencies. To assess frailty status, we were based on the "Valence Score," which consists of measuring: weakness, weight loss, low level of activity, slowness, and little resistance. We found that hearing is significantly lower in older age groups. The mice become frail as they age. The worsening in auditory steady-state responses threshold shifts with age correlates significantly with an increasing frailty. No significant differences were found between both sexes. Our research is, to our knowledge, the first carried out in experimental animals to establish the association between age-related hearing loss and frailty, which would provide a useful tool to evaluate future interventions in mice before translating them into clinical practice.

Background: Phenotypic age acceleration (PhenoAgeAccel) is a potential aging biomarker. While weekend catch-up sleep (WCS) is commonly practiced to compensate for weekday sleep deficits, its relationship with PhenoAgeAccel remains unclear.

Methods: In this cross-sectional study, we analyzed data from 7 683 participants in the National Health and Nutrition Examination Survey. WCS duration was calculated as weekend sleep duration minus weekday sleep duration, and WCS was further defined as WCS duration >0 hour. Multivariable logistic regression adjusted for confounders and subgroup analyses by weekday sleep duration were employed to examine the relationship of WCS with PhenoAgeAccel.

Results: WCS is associated with a modulated risk of PhenoAgeAccel, contingent on the amount of WCS and regular weekday sleep. Specifically, engaging in 0-1 hour of WCS was associated with significantly lower odds of PhenoAgeAccel (odds ratio = 0.80, 95% confidence interval: 0.68-0.94, p = .007) compared to no WCS, particularly among individuals who averaged 7-8 hours of sleep on weekdays (odds ratio = 0.67, 95% confidence interval: 0.49-0.93, p = .016). Conversely, those sleeping less than 6 hours on weekdays benefited from extending WCS beyond 2 hours (odds ratio = 0.65, 95% confidence interval: 0.44-0.97, p = .036). No benefits were observed for those with more than 8 hours of weekday sleep.

Conclusions: WCS is associated with a reduced likelihood of PhenoAgeAccel among individuals with inadequate weekday sleep, particularly those sleeping less than 6 hours or between 7 and 8 hours on weekdays.

Background: Subjective wellbeing (SWB) is a crucial measure of life quality in older adults. Understanding its relationship with frailty may inform strategies to promote healthy aging.

Methods: We analyzed data for older adults aged ≥ 60 years old from Waves 3 and 4 of the China Health and Retirement Longitudinal Study. SWB was measured based on participants' self-reported overall satisfaction with life. A frailty index was developed using the deficit accumulation approach. We conducted a cross-sectional Poisson regression to investigate the relationship between SWB and counts of frailty deficits. Additionally, we conducted a longitudinal analysis to determine the three-year relative risk of clinically significant frailty progression or mortality for different levels of SWB. The analyses were adjusted for individual weights, including adjustments for household nonresponse.

Results: The cross-sectional analysis included 9,702 individuals. After adjusting for covariates, lower baseline life satisfaction was associated with higher counts of frailty deficits (mean deficit counts ratio [95% confidence interval]: 1.66 [1.54, 1.78] for "not satisfied" and 1.06 [1.02, 1.10] for "somewhat satisfied" relative to the reference "very satisfied"). The longitudinal analysis included 8,599 individuals. Participants who were "not satisfied" with life at baseline were at a greater risk of frailty progression compared with those who were "very satisfied" (risk ratio: 1.16 [1.00, 1.35]).

Conclusion: Our study finds that a lower level of SWB is associated with more severe frailty. It is also associated with frailty progression or death. These results emphasize that both psychological wellbeing and physical health are essential components of healthy aging.

Background: Racial/ethnic minoritized groups in the U.S. have higher prevalence of cardiometabolic multimorbidity and experience higher risk of dementia. This study evaluates the relationship between cardiometabolic multimorbidity and dementia onset according to racial/ethnic group in a nationally representative cohort of U.S. middle-aged and older adults.

Methods: Data from the Health & Retirement Study (1998-2018, N=7,960, mean baseline age 59.4 years) and discrete-time survival models were used to estimate differences in the risk of dementia onset, defined by Langa-Weir classification. Models included race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic), chronic disease/multimorbidity categories (no disease, one disease, cardiovascular multimorbidity, metabolic multimorbidity, cardiometabolic multimorbidity, other multimorbidity), age, sex, education, wealth, body-mass index, and proxy status.

Results: Over a mean follow-up of 14.6 years, 7.7% of the participants (n=614) developed dementia. In the fully adjusted model, participants with cardiometabolic multimorbidity had the highest risk of dementia onset (HR:3.27, 95%CI: 2.06,5.21), followed by metabolic (HR:1.83, 95%CI: 1.14,2.94) and cardiovascular (HR:1.81, 95%CI: 1.24,2.64) multimorbidity, relative to participants with no disease. The risk of dementia was significantly greater among Black (HR: 6.40, 95% CI: 3.84,10.67) and Hispanic participants (HR: 4.90, 95% CI: 2.85,8.43) with cardiometabolic multimorbidity, compared to White adults with no disease.

Conclusions: Individuals from racial/ethnic minoritized groups have a higher risk of dementia. The risk of dementia onset was significantly greater for Black and Hispanic participants experiencing cardiometabolic multimorbidity, highlighting the value of intervening on cardiometabolic conditions among middle-age and older adults, in particular those from racial/ethnic minoritized backgrounds to reduce the risk of developing dementia.

The African turquoise killifish Nothobranchius furzeri represents an emerging short-lived model for aging research. Captive strains of this species are characterized by large differences in lifespan. To identify the gene expression correlates of this lifespan differences, we analyzed a public transcriptomic dataset consisting of four different tissues in addition to embryos. We focused on the GRZ and the MZM0410 captive strains, which show a near twofold difference in lifespan, but similar growth and maturation and validated the results in a newly-generated dataset from a third longer-lived strain. The two strains show distinct transcriptome expression patterns already as embryos and the genotype has a larger effect than age on gene expression, both in terms of number of differentially expressed genes and magnitude of regulation. Network analysis detected RNA processing and histone modifications as the most prominent categories upregulated in GRZ that also showed idiosyncratic expression patterns such as high expression of DND is somatic tissues. The short-lived GRZ strain shows transcriptional aging signatures already at sexual maturity (anticipated aging) in all four tissues suggesting that short lifespan is the results of events that occur early in life rather than the progressive accumulation of strain-dependent differences. The GRZ strain is the most commonly used N. furzeri strain in intervention studies and our results warrant replication of at least key intervention studies in longer-lived strains.

Background: The association between subclinical cardiovascular disease (CVD) and cognitive decline in hypertensive adults and the underlying brain pathologies remain unclear. It is also undetermined whether intensifying blood pressure (BP) treatment slows down cognitive decline associated with subclinical CVD.

Methods: We conducted a post hoc analysis of the Systolic Blood Pressure Intervention Trial. Subclinical CVD at baseline was identified by elevated levels of high-sensitivity cardiac troponin T (hs-cTnT≥14 ng/L) and N-terminal pro-B-type natriuretic peptide (NT-proBNP≥125 pg/mL). Global cognitive function and domain-specific measures (memory, processing speed, language, and executive function) were assessed at baseline and follow-up (years 2, 4, and 6) in 2733 participants. White matter lesions, cerebral blood flow, and brain tissue volume were assessed by MRI at baseline and years 4 in a subset of 639 participants.

Results: Both elevated hs-cTnT and NT-proBNP levels at baseline were associated with accelerated cognitive decline across all domains after adjusting for potential confounding factors. The group with elevated levels of both cardiac biomarkers showed the fastest decline, with a larger annual decline rate of 0.033 (95% CI: 0.024-0.041) in the z-score of global cognitive function compared to the group with normal levels. Elevated levels of both biomarkers were also associated with a faster progression in white matter lesions, but not with changes in total brain tissue volume or cerebral blood flow. Intensive BP treatment did not attenuate these associations compared to standard treatment.

Conclusions: Subclinical CVD may contribute to faster white matter lesion progression and accelerated cognitive decline in patients with hypertension, regardless of intensive BP treatment.

Background: Poor muscle strength is a risk factor for disability; nonetheless its discriminative capacity in identifying people who will become disabled is poor. We evaluated whether muscle power, which also is a risk factor for disability, has better discriminative capacity compared to muscle strength.

Methods: We used data from the population based InCHIANTI study. Our outcome measure was the loss of at least one basic or instrumental activity of daily living between baseline and 3-years follow-up visit. Body weight standardized knee isometric strength and leg power (power rig) were used as exposure variables. Discriminative capacity was estimated using the area under the receiver operating curves (ROC). Both strength and power were dichotomized as below versus equal of above sex-specific first quartile. Sensitivity, specificity, and positive/negative predictive values (PPV, NPV) were calculated.

Results: We included 763 participants (415 women), with a mean age of 73.5 years (SD 6.4).In men, using muscle strength we obtained an AUC of 0.70, with sensitivity=0.45, specificity=0.80, PPV=0.27, and NPV=0.90; using muscle power we obtained an AUC of 0.82, sensitivity=0.73, specificity=0.86, PPV=0.46, and NPV=0.95.In women, using muscle strength we obtained an AUC of 0.62, with sensitivity=0.39, specificity=0.81, PPV=0.39, and NPV=0.81; using muscle power we obtained an AUC=0.69, sensitivity=0.40, specificity=0.83, PPV=0.42, and NPV=0.82.

Conclusions: We found that in men muscle power had better discriminative capacity, especially higher sensitivity, compared to muscle strength for prediction of worsening disability. No meaningful difference in overall discriminative capacity were found in women.

As the healthcare burden caused by an increasingly aging population rapidly rises, a pressing need exists for innovative geroscience research that can elucidate aging mechanisms and precipitate the development of therapeutic interventions to support healthy aging. The Fifth Annual Midwest Aging Consortium Aging Research symposium, held from April 28-30, 2024, was hosted by The Ohio State University in Columbus, Ohio and featured presentations from investigators across the Midwestern United States. This report summarizes the research presented at the symposium, whose topics included cellular senescence and the aging brain, metabolism and metabolic interventions, nutrition, redox mechanisms and biomarkers, and stress mechanisms. Abstract presentations and short talks highlighted early-stage and young investigators, while two keynote presentations anchored the symposium. Overall, this symposium showed the robustness of aging research in the Midwest and underscored the advantages of a collaborative approach to geroscience research.

Cellular senescence is a pivotal contributor to aging and age-related diseases. The targeted elimination of senescent cells, known as senolysis, has emerged as a promising therapeutic strategy for mitigating these conditions. Glutaminase 1 (GLS1), a key enzyme in the glutaminolysis pathway, has been implicated in various cellular senescence processes. However, its specific role in senescent renal tubular epithelial cells (TECs) remains unclear. This study investigates the role and underlying mechanisms of GLS1 in senescent TECs. Using D-galactose (D-gal)-induced senescence of HK-2 cells, we found that GLS1 inhibition eliminated senescent TECs by promoting excessive mitochondrial permeability transition pore (mPTP) opening. Mechanistically, the excessive mPTP opening is associated with upregulation of mitofusin 1 (MFN1). Inhibition of GLS1 in D-gal-treated HK-2 cells induced a shift in mitochondrial dynamics from fission to fusion, accompanied by a significant increase in MFN1 expression. Knocking down MFN1 reduced the mPTP opening and the expression of mPTP-related genes (PPIF, VDAC and BAX) in cells co-treated with D-gal and the GLS1 inhibitor BPTES. Moreover, treatment of aged mice with BPTES specifically eliminated senescent TECs and ameliorated age-associated kidney disease. These findings reveal that GLS1 inhibition eliminate senescent TECs by promoting excessive mPTP opening, suggesting that targeting GLS1 may be a novel senolytic strategy for alleviating aging-related kidney diseases.