Aging & Longevity

Once taken into consideration, sex differences in neurological diseases emerge in abundance: (i) Stroke severity is significantly higher in females than in males, (ii) Alzheimer's disease (AD) pathology is more pronounced in females, and (iii) conspicuous links with hormonal cycles led to female-specific diagnoses, such as catamenial migraines and epilepsy. While these differences receive increasing attention in isolation, they likely link to similar processes in the brain. Hence, this review...

Menopause is a major biological transition that may influence women's late-life brain health. Earlier estrogen depletion-via earlier menopause-has been associated with increased risk for Alzheimer's disease (AD). Synaptic dysfunction also incites and exacerbates AD progression. We investigated whether age at menopause and synaptic health together influence AD neuropathology and cognitive trajectories using clinical and autopsy data from 268 female decedents in the Rush Memory and Aging Project....

Elucidating the downstream impact of exogenous hormones on the aging brain will have far-reaching consequences for understanding why Alzheimer's disease (AD) predominates in women almost twofold over men. We tested the extent to which menopausal hormone therapy (HT) use is associated with later-life amyloid-β (Aβ) and tau accumulation using PET on N = 146 baseline clinically normal women, aged 51 to 89 years. Women were scanned over a 4.5-year (SD, 2.1; range, 1.3 to 10.4) and 3.5-year (SD, 1.5;...

Cross-sectional age-skill profiles suggest that cognitive skills start declining by age 30 if not earlier. If accurate, such age-driven skill losses pose a major threat to the human capital of societies with rapidly aging populations. We estimate actual age-skill profiles from individual changes in literacy and numeracy skills at different ages. We use the unique German longitudinal component of the Programme of the International Assessment of Adult Competencies (PIAAC-L) that retested a large...

Advanced aging is associated with robust changes in neural activity. In addition to the well-established age-related slowing of the peak alpha frequency, there is a growing body of evidence showing that older age is also associated with changes in alpha power and beta power. Despite the important progress that has been made, the interacting effects of age and frequency band have not been directly tested in sensor and source space while controlling for aperiodic components. In the current study...

A significant challenge in multi-omic geroscience research is the collection of high quality, fit-for-purpose biospecimens from a diverse and well-characterized study population with sufficient sample size to detect age-related changes in physiological biomarkers. The Dog Aging Project designed the precision cohort to study the mechanisms underlying age-related change in the metabolome, microbiome, and epigenome in companion dogs, an emerging model system for translational geroscience research....

Attentional states reflect the changing behavioral relevance of stimuli in one's environment, having important consequences for learning and memory. Supporting well-established cortical contributions, attentional states are hypothesized to originate from subcortical neuromodulatory nuclei, such as the basal forebrain (BF) and locus coeruleus (LC), which are among the first to change with aging. Here, we characterized the interplay between BF and LC neuromodulatory nuclei and their relation to...

Cancer is an age-related disease, but the interplay between cancer and aging is complex and their shared molecular drivers are deeply intertwined. This Review provides an overview of how different biological pathways affect cancer and aging, leveraging evidence mainly derived from animal studies. We discuss how genome maintenance and accumulation of DNA mutations affect tumorigenesis and tissue homeostasis during aging. We describe how age-related telomere dysfunction and cellular senescence...

Consumer-grade mobile devices are used by billions worldwide. Their ubiquity provides opportunities to robustly capture everyday cognition. 'Intuition' was a remote observational study that enrolled 23,004 US adults, collecting 24 months of longitudinal multimodal data via their iPhones and Apple Watches using a custom research application that captured routine device use, self-reported health information and cognitive assessments. The study objectives were to classify mild cognitive impairment...

CONCLUSION: Patient-reported adverse drug events are more prevalent in older co-morbid patients in Liaoning province. Female, numbers of daily drugs, fall history with 1 year and poor medication compliance were significantly and independently associated with adverse drug events. These findings may provide informative interventions for the medication management in elderly patients living with multimorbidity.

CONCLUSIONS: The VI-ACE-III showed good sensitivity and specificity for assessing dementia and MCI in Arabic-speaking elderly individuals with visual impairment (VI) in Egypt. Regular screening and interventions are crucial for managing and preventing the deterioration of cognitive dysfunction and vision impairment in the elderly population.

Cancer immunotherapy has revolutionized treatment paradigms, but its efficacy is often curtailed by T-cell exhaustion and the suppressive tumour microenvironment. Recent studies reveal a novel mechanism of T-cell demise termed ammonia-induced cell death (AICD), which significantly impacts effector CD8+ T-cell survival and function. This phenomenon arises from metabolic reprogramming during immune activation, wherein heightened glutamine metabolism leads to the accumulation of toxic ammonia...

The aim of this study is to investigate the association between retinal age gap and multimorbidity. Retinal age gap was calculated based on a previously developed deep learning model for 45,436 participants. The number of age-related conditions reported at baseline was summed and categorized as zero, one, or at least two conditions at baseline (multimorbidity). Incident multimorbidity was defined as having two or more age-related diseases onset during the follow-up period. Linear regressions...

Physical exercise has been associated with healthier aging trajectories, potentially preventing or mitigating age-related declines. This occurs through a complex, yet poorly characterized network of multi-organ interactions involving mitochondrial, inflammatory, and cell death/survival pathways. Here, we comprehensively evaluated the 12-week VIVIFRAIL multicomponent exercise protocol in physically frail (n = 16, mean age 81.4 ± 5.6) and robust (n = 50, mean-age 73.6 ± 4.7) old individuals....

The presence of senescent cells causes age-related pathologies since their removal by genetic or pharmacological means, as well as possibly by exercise, improves outcomes in animal models. An alternative to depleting such cells would be to rejuvenate them to promote their return to a replicative state. Here we report that treatment of non-growing senescent cells with low-frequency ultrasound (LFU) rejuvenates the cells for growth. Notably, there are 15 characteristics of senescent cells that are...

CONCLUSION: In wrist and ankle joints, the age-related decline in proprioception is limited to the sense of force, especially for low forces. This nonuniform decline in proprioception across proprioceptive senses and testing conditions could reflect a decline in the central processing of proprioceptive information.

Biomarkers of aging are indispensable for testing interventions. While promising, the recent focus on molecular aspects should not detract from the functional parameters for which excellent correlation with mortality, and ample clinical human data exist.

Testicular aging is associated with declining reproductive health, but the molecular mechanisms are unclear. Here we generate a dataset of 214,369 single-cell transcriptomes from testicular cells of 35 individuals aged 21-69, offering a resource for studying testicular aging and physiology. Machine learning analysis reveals a stronger aging response in somatic cells compared to germ cells. Two waves of aging-related changes are identified: the first in peritubular cells of donors in their 30s,...

Understanding the key drivers of brain aging is essential for effective prevention and treatment of neurodegenerative diseases. Here, we integrate human brain and physiological data to investigate underlying mechanisms. Functional MRI analyses across four large datasets (totaling 19,300 participants) show that brain networks not only destabilize throughout the lifetime but do so along a nonlinear trajectory, with consistent temporal "landmarks" of brain aging starting in midlife (40s)....

Rnd3 is a small Rho-GTPase that has been implicated in various cardiovascular diseases. Yet, its role in diabetes-induced cardiomyocyte senescence remains unknown. Here we tested the role of Rnd3 in cardiomyocyte senescence and diabetic cardiomyopathy (DCM). The expression of Rnd3 was found to be reduced in peripheral blood mononuclear cells from diabetic patients and correlated negatively with age but positively with cardiac function. In 96-week-old Sprague Dawley (SD) rats, cardiac function...