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

Background: As the global population ages healthcare challenges are escalating. Frailty, a clinical syndrome characterized by decreased reserve and resilience to stressors, is critically linked to adverse health outcomes in older adults. However, artificial intelligence (AI)-driven technologies offer promising solutions for revolutionizing older individuals care and enhancing senior health and independence.

Objective: This paper explores how AI-driven technologies, including wearables, nonwearable devices, and wireless systems, are transforming senior care. These innovations enable continuous health monitoring, fall detection, medication adherence, and cognitive assistance.

Recent findings: Recent advancements in sensor technology, machine learning/AI algorithms, and user interface design have made these technologies more effective and accessible to older adults. Key benefits include early health issue detection, improved medication adherence, reduced hospitalizations, extended independent living, and improved quality of life. Privacy concerns, ease of use, and technology adoption are challenges that must be addressed.

Conclusion: Thoughtfully designed AI wearables and supportive policies and infrastructure can significantly enhance seniors' quality of life while reducing caregiver burden and healthcare costs. As technology advances, AI-driven solutions across wearable, nonwearable, and wireless devices are set to become indispensable in global strategies for healthy aging.

Rapamycin has demonstrated significant lifespan-extending effects across a variety of model organisms, positioning it as one of the most promising antiaging agents currently under investigation. Nonetheless, chronic administration of rapamycin may induce diverse adverse reactions, primarily due to its influence on energy metabolism. Here, using Drosophila melanogaster as a model, we show that rapamycin significantly alters feeding behaviors in a dose-dependent manner. Specifically, both long-term and short-term administration of the optimal life-extending dose of rapamycin decreases the protein preference while increasing sugar intake in female flies. Utilizing a chemically defined diet, we identified that these alterations in amino acid and sugar feeding preferences occur as early as the second day of rapamycin exposure, preceding any detectable decline in fecundity. Furthermore, rapamycin also modifies amino acid preference even in taste-blind females, indicating that postingestive nutritional learning mechanisms, independent of food taste value, are sufficient to mediate the effects of rapamycin on feeding behavior. However, such changes in macronutrient preferences were absent in males and sterile mutant females. Collectively, our study suggests that the modification of feeding behavior could be a non-negligible side effect of rapamycin treatment, and this effect is influenced by both sex and reproductive status.

Background: Epigenetic aging measures have promise as surrogate health outcomes in randomized control trials and observational cohort studies. The value of these measures, however, will reflect the extent to which they are associated with prospective health outcomes in real-world medical settings.

Methods: Using data from 2 216 post-9/11 veterans from the VISN 6 MIRECC's Post-Deployment Mental Health Study, we examined whether accelerated epigenetic aging, assessed by DunedinPACE, was associated with prospective chronic disease morbidity, predicted healthcare costs, and mortality over an average of 13.1 years of electronic health record follow-up.

Results: Veterans with faster DunedinPACE aging scores developed more chronic disease over the subsequent 5 years (RR, 1.25; 95% CI, 1.14-1.36), 10 years (RR, 1.31; 95% CI, 1.21-1.40), and 15 years (RR, 1.36; 95% CI, 1.22-1.52). Faster aging scores were also associated with increases in predicted healthcare costs over the next 5 years (β = 0.08; 95% CI, 0.03-0.13), 10 years (β = 0.23, 95% CI, 0.15-0.31), and 15 years (β = 0.21; 95% CI, 0.11-0.30). Faster DunedinPACE aging scores were associated with greater risk for incident myocardial infarction (84%), stroke (38%), diabetes (56%), cancer (25%), liver disease (44%), and renal disease (34%), as well as greater risk of mortality due to all-causes (38%) and chronic disease (74%). These results remained when adjusting for demographic, biomarker, and smoking covariates.

Conclusions: Our findings suggest DunedinPACE is a biomarker of accelerated aging that is prospectively associated with chronic disease morbidity and mortality, as assessed using health records from an integrated healthcare system.

The aging of the population is a global concern. In the post-coronavirus disease 2019 (COVID-19) pandemic era, there are no effective methods to identify aging acceleration due to infection. In this study, we conducted whole-transcriptome sequencing on peripheral blood samples from 35 healthy individuals (22-88 years old). By analyzing the changes in mRNA, lncRNA, and miRNA expression, we investigated the characteristics of transcriptome alterations during the aging process. ceRNA networks were constructed, and 10 genes (CD248, PHGDH, SFXN2, MXRA8, NOG, TTC24, PHYKPL, CACHD1, BPGM, and TWF1) were identified as potential aging markers and used to construct an aging clock. Moreover, our aging clock categorized individuals into slow-, average-, and quick-aging groups, highlighting a link between accelerated aging and infection-related clinical parameters. Pseudotime analysis further revealed 2 distinct aging trajectories, corroborating the variations in the aging rate identified by the aging clock. Furthermore, we validated the results using the OEP001041 data set (277 healthy individuals aged 17-75), and data sets comprising patients with infectious diseases (n = 1 558). Our study revealed that infection accelerates aging via increased inflammation and oxidative stress in infectious disease patients. Besides, the aging clock exhibited alterations after infection, highlighting its potential for assessing the aging rate after patient recovery. In conclusion, our study introduces a novel aging clock to assess the aging rate in healthy individuals and those with infections, revealing a strong link between accelerated aging and infections through inflammation and oxidative stress. These findings offer valuable insights into aging mechanisms and potential strategies for healthy aging.

Aging is a complex process influenced by mechanisms operating at numerous levels of functioning. Multiple biomarkers of age have been identified, yet we know little about how the different alternative age indicators are intertwined. In the Berlin Aging Study II (nmin = 328; nmax = 1 517, women = 51%; 14.27 years of education), we examined how levels and 7-year changes in indicators derived from blood assays, magnetic resonance imaging brain scans, other-ratings, and self-reports converge among older adults. We included 8 epigenetic biomarkers (incl. 5 epigenetic "clocks"), a BioAge composite from clinical laboratory parameters, brain age, skin age, subjective age, subjective life expectancy, and subjective health horizon. We found moderate associations within aging domains, both cross-sectionally and longitudinally over 7 years. However, associations across different domains were infrequent and modest. Notably, participants with older BioAge had correspondingly older epigenetic ages. Our results suggest that different aging clocks are only loosely interconnected and that more specific measures are needed to differentiate healthy from unhealthy aging.

Background: The Life's Essential 8 (LE8) is a composite metric including 4 health behaviors (diet, physical activity, nicotine exposure, and sleep) and 4 health factors (body mass index, nonhigh-density lipoprotein cholesterol, blood glucose, and blood pressure). This study aimed to describe the cardiovascular health (CVH) metrics promoted by LE8 in nonagenarians and to investigate their relationship with mortality at 5 and 10 years.

Methods: This study was conducted within the framework of the Mugello Study, a longitudinal survey on nonagenarians living in the Mugello area (Tuscany, Italy). One-hundred and fifty-seven subjects (42 males and 115 females, median age 92 years) were administered a series of validated questionnaires and underwent instrumental examinations and blood withdrawal. CVH metrics were calculated according to LE8 guidelines. Physical activity and sleep duration were quantitatively estimated using a monitor device.

Results: In the male group, after 5 and 10 years of follow-up, a higher Health Behavior score was associated with a lower risk of all-cause mortality (HR: 0.963, p = .005 and HR: 0.972, p = .020; after 5 and 10 years). Differently, in the female group, no significant association was observed between the LE8 total score and subscores and different risk of mortality after 5 and 10 years from the interview.

Conclusions: These findings highlight the importance of potentially modifiable behaviors in improving survival. They support resource investments to address the needs of individuals in this stage of life and encourage them to be empowered and actively engage in health-promoting behaviors.

Aging is the greatest risk factor for a multitude of age-related diseases including sarcopenia-the loss of skeletal muscle mass and strength-which occurs at remarkable rates each year. There is an unmet need not only to understand the mechanisms that drive sarcopenia but also to identify novel therapeutic strategies. Given the ease and affordability of husbandry, along with advances in genomics, genome editing technologies, and imaging capabilities, teleost models are increasingly used for aging and sarcopenia research. Here, we explain how teleost species such as zebrafish, African turquoise killifish, and medaka recapitulate many of the classical hallmarks of sarcopenia, and discuss the various dietary, pharmacological, and genetic approaches that have been used in teleosts to understand the mechanistic basis of sarcopenia.

Background: Although physical activity (PA) is known to improve physical function (PF), and functional decline impacts the capacity to engage in PA, the reciprocal relationship between PA and PF remains unclear.

Methods: Data were from participants in the 1921-1926 cohort of the Australian Longitudinal Study on Women's Health (N = 8 238). PA and PF were assessed at 3-year intervals from 1999 (73-78 y) to 2011 (85-90 y). Group-based trajectory modeling was used to identify PA and PF trajectories, and associations between PA and PF were examined using mixed-effects models and restricted cubic spline modeling.

Results: Three trajectories for PA and PF were identified: Low, Moderate, and High. Women in the High PA group maintained high PF and did not reach the starting PF level of the Low PA group (at age 73) until they were 87. Similarly, women in the High PF group maintained higher PA than those in the other groups. Women in the Low PF group never met PA guidelines and had PF scores below the disability threshold throughout the study. Restricted cubic splines showed that higher PA was associated with better PF 3 years later, and vice versa, indicating that PA and PF influence each other.

Conclusion: There are reciprocal relationships between PF and PA; higher levels of PA promote better PF, and higher PF may help slow the decline in PA. Although rates of decline in PF show little variation with PA in women during their 80s, habitually high PA confers considerable benefits, contributing to additional years of healthy life.

The active peptide hormone angiotensin II (Ang II) mediates the vast majority of the renin-angiotensin system action, mainly through activation of Ang II type-1 receptor (AT1R). AT1R expression peaks in newborn males and decreases toward the adult age, and it is shown to exhibit an inhibitory effect on human chorionic gonadotropin-stimulated steroidogenesis in Leydig cells (LCs), as well as a promoting effect on smooth muscle and endothelial cell senescence. However, whether hyperactivation of the AT1R signaling exerts any effects on LC senescence, which could provide insights into hypogonadism mechanisms for aging males, remains unexplored. We herein reported that AT1R expression was significantly upregulated in aged human and rat testes. Transgenic overexpression of AT1R in LCs mimicked multiple late-onset hypogonadism phenotypes, including acceleration of LC senescence, defective steroidogenesis and spermatogenesis, and increased inflammation and oxidative stress. One of the core biochemical events underpinning AT1R action was the AT1R-induced enhancement of the interaction between murine double minute 2 and the p65 subunit of nuclear factor-kappa B, consequently augmenting polyubiquitination and activation of p65, in a p38-dependent manner. Conversely, repression of AT1R activity ameliorated LC senescence and rescued testicular steroidogenesis in old rats. Together, forced expression of AT1R within the testicular interstitium potentiates aging-related traits in LCs, thereby leading to fertility impairment with defective steroidogenesis and spermatogenesis in male rodents. Our systematic analysis also indicates that blocking the Ang II/AT1R signal might be beneficial in intervening in disorders of late-onset hypogonadism in old males.

Background: Age-related changes in adipose tissue affect chronic medical diseases and mobility disability but mechanism remains poorly understood. The goal of this study is to define methods for phenotyping unique characteristics of adipose tissue from older adults.

Methods: Older adults enrolled in study of muscle, mobility, and aging selected for the adipose tissue ancillary (SOMMA-AT; N = 210, 52.38% women, 76.12 ± 4.37 years) were assessed for regional adiposity by whole-body magnetic resonance (AMRA) and underwent a needle-aspiration biopsy of abdominal subcutaneous adipose tissue (ASAT). ASAT biopsies were flash frozen, fixed, or processed for downstream applications and deposited at the biorepository. Biopsy yields, qualitative features, adipocyte sizes, and concentration of adipokines secreted in ASAT explant conditioned media were measured. Inter-measure Spearman correlations were determined.

Results: Regional, but not total, adiposity differed by sex: women had greater ASAT mass (8.20 ± 2.73 kg, p < .001) and biopsy yield (3.44 ± 1.81 g, p < .001) than men (ASAT = 5.95 ± 2.30 kg, biopsy = 2.30 ± 1.40 g). ASAT mass correlated with leptin (r = 0.54, p < .001) and not resistin (p = .248) and adiponectin (p = .353). Adipocyte area correlated with ASAT mass (r = 0.34, p < .001), BMI (r = 0.33, p < .001), adiponectin (r = -0.22, p = .005) and leptin (r = 0.18, p = .024) but not with resistin (p = .490).

Conclusion: In addition to the detailed ASAT biopsy processing in this report, we found that adipocyte area correlated with ASAT mass, and both measures related to some key adipokines in the explant conditioned media. These results, methods, and biological repositories underscore the potential of this unique cohort to impact the understanding of aging adipose biology on disease, disability, and other aging tissues.