Aging & Longevity

To further understand whether childhood maltreatment (CM) is associated with indicators of accelerated cognitive aging, this study investigated whether CM moderated the relationship of age with gray matter volume (GMV) and executive functions among community adults aged 21-55. Participants (N = 225) underwent MRI scanning, and a composite measure of executive functions was computed across measures of inhibitory control, switching, and working memory. To interpret interactions, we created high...

Accumulation of senescent cells is a key contributor to multiple diseases across the lifespan, including metabolic dysfunction. We previously demonstrated that elimination of senescent cells using senolytic drugs alleviates obesity-induced metabolic dysfunction. However, the contribution of senescent endothelial cells to metabolic disorders remains elusive. Hence, we crossed mice that allow selective elimination of senescent cells (p16^(Ink4a)-LOX-ATTAC mice) with Tie2-Cre mice...

Menopause is a hallmark of women's aging and is frequently portrayed as a medical issue. It also encompasses social and biological aspects often neglected and not well-understood, leaving women with insufficient support and attention. With the decline in estrogen levels, starting years before menopause is fully established, women experience various physical symptoms, and the risk of many age-related diseases increases sharply soon after these hormonal changes occur. Notably, these hormonal...

CONCLUSIONS AND IMPLICATIONS: High-risk prescribing is common in those living with dementia and varies by sociodemographic factors. Regular, targeted medication reviews are needed to ensure quality use of medicines in this population.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of motor neurons, leading to fatal muscle paralysis. Familial forms of ALS (fALS) account for approximately 10% of cases. Alterations of mitochondrial functions have been proposed to contribute to disease pathogenesis. Here, we employed a direct conversion (DC) technique to generate induced motor neurons (iMN) from skin fibroblasts to investigate mitochondrial phenotypes in a patient-derived disease relevant cell...

Spermine, a pivotal player in biomolecular condensation and diverse cellular processes, has emerged as a focus of investigation in aging, neurodegeneration, and other diseases. Despite its significance, the mechanistic details of spermine remain incompletely understood. Here, we describe the distinct modulation by spermine on Alzheimer's Tau and Parkinson's α-synuclein, elucidating their condensation behaviors in vitro and in vivo. Using biophysical techniques including time-resolved SAXS and...

Loss of Fibronectin (FN) from the skeletal muscle stem cell (MuSC) niche represents a root cause of regenerative failure in aging. While FN has pleiotropic functions during healthy skeletal muscle regeneration, it remains unclear how aging affects its spatiotemporal specificity for MuSCs. Here, we demonstrate that activated MuSCs secrete an autoregulatory FN splice variant containing the EDB extra domain (EDB(+) FN), which is not expressed by accessory cells in the niche. EDB(+) FN splicing in...

Brain atrophy is a key factor behind episodic memory loss in aging, but the nature and ubiquity of this relationship remains poorly understood. This study leverages 13 longitudinal datasets, including 3737 cognitively healthy adults (10,343 MRI scans; 13,460 memory assessments), to determine whether brain change-memory change associations are more pronounced with age and genetic risk for Alzheimer's Disease. Both factors are associated with accelerated brain decline, yet it remains unclear...

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Cognitive impairment is associated with perturbations of fine-tuned neuroimmune interactions. At the molecular level, alterations in cellular metabolism can compromise brain function, driving structural damage and cognitive deficits. In this Review, we focus on the bidirectional interactions between microglia, the brain-resident immune cells and neurons to dissect the metabolic determinants of brain resilience and cognition. We first outline these metabolic pathways during development and adult...

Geroscience aims to target the aging process to extend healthspan. However, even isogenic individuals show heterogeneity in natural aging rate and responsiveness to pro-longevity interventions, limiting translational potential. Using RNAseq analysis of young, isogenic, subpopulations of Caenorhabditis elegans selected solely on the basis of the splicing pattern of an in vivo minigene reporter that is predictive of future life expectancy, we find a strong correlation in young animals between...

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CONCLUSION AND RELEVANCE: Findings suggest that changes in physiological parameters describing patterns of chronic inflammation are associated with measurable cognitive changes in aging cats, in the absence of overt clinical disease, which is consistent with the concept of inflammaging. Routine monitoring of standard bloodwork and BCS may offer an accessible means of tracking chronic subclinical inflammation and predicting cognitive aging in senior feline patients. These results highlight the...

Parvalbumin-expressing inhibitory neurons (PVNs) stabilize cortical network activity, generate gamma rhythms, and regulate experience-dependent plasticity. We found that PVNs act like a volume knob in the mouse auditory cortex (ACtx), bi-directionally adjusting neural and perceptual sensitivity to sound level over a 20 dB range. PVN-based gain adjustments were "sticky," such that a single bout of PVN activation at 40 Hz-but not at 1 or 70 Hz-sustainably dampened ACtx sound responsiveness,...

Identifying practical ways to counteract aging and associated degenerative disorders is urgently needed. We performed deep molecular profiling and functional assessments in aging male mice to show that glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment broadly counteracts age-related changes. In mice treated with a GLP-1RA from 11 months for 30 weeks, we observed strong body-wide multi-omic age-counteracting effects and improved selected physical functions. Importantly, the effects...

Fall detection systems are crucial for ensuring the safety of older adults, given the potential for severe injuries resulting from falls. However, developing accurate and reliable detection methods faces challenges due to the rarity of fall events and limited training data. This review provides an in-depth examination of recent progress in fall detection technologies for older adults, with particular attention to addressing the scarcity of data. This review is novel in that it integrates...

Adipocyte deposition is believed to be a primary characteristic of age-related thymic involution, but the underlying cellular and molecular mechanisms remain unknown. We show here that thymic mesenchymal stromal cells (tMSCs) have a higher tendency to differentiate into adipocytes and melanocortin-2 receptor accessory protein (MRAP) is a potential driver of tMSCs adipogenesis. Furthermore, we discover that thymosin-α1 promotes MRAP expression in tMSCs through FoxO1 signaling pathway....

This study investigates how the transition to retirement influenced the uptake of COVID-19 vaccination in Europe. We employed a quasi-experimental regression discontinuity design to assess the impact of retirement on COVID-19 vaccination, accounting for unobserved confounding and controlling for factors such as subjective health status, age, vaccination for other diseases, medication use, cancer diagnosis, and internet use. We used individual-level data from the Corona Surveys of the Survey of...

Obstructive sleep apnea (OSA) accelerates cardiovascular aging through intermittent hypoxia (IH). We exposed mice to 22 months of IH, modeling lifelong OSA. Compared to controls, IH mice exhibited higher mortality, elevated blood pressure, impaired systolic and diastolic function, vascular stiffening, reduced coronary reserve, and ECG abnormalities. These findings suggest that chronic IH significantly exacerbates cardiovascular decline with aging, underscoring the importance of early OSA...

Collagen supplementation has gained attention with increasing claims regarding its beneficial effects on healthy aging based on clinical observations and lifespan extension in pre-clinical models; however, how and which part of an ingested collagen promotes healthy longevity is unknown. Here, we identified the minimal required unit of ingested collagen, which consists of the proper ratio of three glycine to one proline to one hydroxyproline that was sufficient to increase the motility-healthspan...