Aging & Longevity

CONCLUSIONS AND IMPLICATIONS: Sensory impairments are associated with an increased risk of organic mental disorders, potentially partly mediated by accelerated biological aging, with social support demonstrating a significant moderating effect. The gradient of risk across impairment types and the substantial potential mediating effect of biological age acceleration are consistent with multiple pathways linking sensory and cognitive health. These findings indicate that comprehensive interventions...

Retinal degeneration (RD), a group of progressive diseases marked by the loss of retinal neurons. Aging contributes to the gradual decline in cellular function, which, in turn, exacerbates the pathogenesis of RD through complex molecular mechanisms, including aberrant gene expression, impaired cellular signaling pathways, oxidative stress, and inflammation. The pivotal role of epigenetic histone modifications in mediating the onset and progression of neurological disorders has garnered...

Hematopoietic stem cell (HSC) transplantation offers a cure for a variety of blood disorders, predominantly affecting the elderly; however, its application, especially in this demographic, is limited by treatment toxicity. In response, we employ a murine transplantation model based on low-intensity conditioning protocols using antibody-mediated HSC depletion. While aging presents a significant barrier to effective HSC engraftment, optimizing HSC doses and non-genotoxic targeting methods greatly...

The folate and methionine cycles (Met-C) are regulated by vitamin B12 (B12), obtained exclusively from diet and microbiota. Met-C supports amino acid, nucleotide, and lipid biosynthesis and provides one-carbon moieties for methylation reactions. While B12 deficiency and polymorphisms in Met-C genes are clinically attributed to neurological and metabolic disorders, less is known about their cell-non-autonomous regulation of systemic physiological processes. Using a B12-sensitive Caenorhabditis...

Aging is one of the most prominent risk factors for neurodegeneration, yet the molecular mechanisms underlying the deterioration of old neurons are mostly unknown. To efficiently study neurodegeneration in the context of aging, we transdifferentiated primary human fibroblasts from aged healthy donors directly into neurons, which retained their aging hallmarks, and we verified key findings in aged human and mouse brain tissue. Here we show that aged neurons are broadly depleted of RNA-binding...

Jansen's metaphyseal chondrodysplasia (JMC) is a rare disorder caused by activating mutations in the parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor (PTH1R). Patients exhibit short stature, dysmorphic bones, and severe growth plate abnormalities, as well as hypercalcemia, hypercalciuria, hypophosphatemia, and reduced plasma PTH levels. Humanized PTH1R (hPTH1R) mice expressing the H223R-hPTH1R JMC mutation die early without breeding. We therefore generated and characterized a...

Bisphenol A (BPA) substitutes are widely used as food contact materials and consumer products, while the effects of pathophysiologically relevant concentrations of BPA substitutes on aging remain unclear. In this study, we used Caenorhabditis elegans (C. elegans) to investigate the effects of five BPA substitutes [bisphenol S (BPS), bisphenol B, bisphenol F (BPF), tetramethyl BPF, and 4,4'-(Perfluoropropane-2,2-diyl)diphenol] at pathophysiologically relevant exposure levels during aging and...

Recent advances in isolating cells based on visual phenotypes have transformed our ability to identify the mechanisms and consequences of complex traits. Micronucleus (MN) formation is a frequent outcome of genome instability, triggers extensive changes in genome structure and signaling coincident with MN rupture, and is almost exclusively defined by visual analysis. Automated MN detection in microscopy images has proved challenging, limiting discovery of the mechanisms and consequences of MN....

The loss of bone volume during aging is common in both men and women and can have substantial negative health impacts. Weakened bones can lead to fractures which in turn can result in hospitalization, decreased quality of life, and early death. The post-diagnosis treatment of osteoporosis has received the bulk of attention with less research focused on prevention and modifiable risk factors such as nutrition. Calcium and vitamin D supplementation has provided limited skeletal benefit in healthy...

A major aging hallmark is the accumulation of cellular senescence burden. Over time, senescent cells contribute to tissue deterioration through chronic inflammation and fibrosis driven by the senescence-associated secretory phenotype (SASP). The human ovary is one of the first organs to age, and prominent age-related fibroinflammation within the ovarian microenvironment is consistent with the presence of senescent cells, but these cells have not been characterized in the human ovary. We thus...

Functional decline of the central nervous system (CNS) is driven by the breakdown of the blood-brain barrier (BBB) and attendant inflammation, all hallmarks of age-related neurodegeneration. Despite intense interest in how the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway impacts neurodegenerative processes in aging, its role in shaping these features of CNS fate during physiological aging remains unclear. Here, using physiologically aged mice, we uncovered an...

CONCLUSIONS AND IMPLICATIONS: About half of older adults exhibit domain-specific deficits, suggesting tailored interventions are essential. Profile 5 needs comprehensive strategies, whereas orientation-focused training could benefit profiles 2, 3, and 4. Demographic factors-particularly age, ethnicity, and income-should guide customization to enhance intervention participation and adherence.

Although cancer treatment strategies have made considerable progress in recent decades, the challenge of selectively killing tumor cells while minimizing damage to healthy tissue remains. Radiotherapy (RT) continues to be crucial for tumor growth control when combined with surgery, chemotherapy, and immunotherapy. RT effectiveness depends on factors such as cancer type, tumor features, and the choice of external or internal treatment. Given its non-invasive nature and low systemic toxicity, RT...

Although animal studies have linked cellular senescence to the pathogenesis and complications of type 2 diabetes mellitus (T2DM), there is a paucity of corroborating data in humans. Thus, we measured a previously validated marker for senescent cell burden in humans, T-cell expression of p16 mRNA, along with additional biomarkers, to compare the senescence phenotypes of postmenopausal control (lean, N = 37) and T2DM (N = 27) participants. To control for effects of obesity alone, we included a...

A healthy nervous system is reliant upon an efficient transport network to deliver essential cargoes throughout the extensive and polarised architecture of neurons. The trafficking of cargoes, such as organelles and proteins, is particularly challenging within the long projections of neurons, which, in the case of axons, can be more than four orders of magnitude longer than cell bodies. It is therefore unsurprising that disruptions in axonal transport have been reported across neurological...

Population aging increases the risk of falls, particularly among postmenopausal women, which can negatively impact their quality of life. Research suggests that multifactorial exercise programmes can help reduce this risk. This study evaluates the effectiveness of an exercise program based on Adapted Utilitarian Judo (JUA) in enhancing older adults' ability to safely manage falls; in this study called "fall competence". Fall competence can be defined as having the knowledge how to fall safely,...

Spermidine is a natural polyamine found in living organisms. In human, the level of spermidine declines with aging. Emerging lines of evidence indicates that supplementation of spermidine favors the improvement of memory performance and cognition function. In this article, recent findings regarding the metabolism of spermidine under pathophysiological conditions are discussed. This review emphasizes the recent mechanistic insights into the memory- and cognition-facilitating effects of...

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Senescent cells accumulate with aging and are associated with several age-associated diseases and functional declines. Eliminating senescent cells with senolytics improves aging phenotypes in mouse models and may improve the health of people with chronic diseases. To date, very few senotherapeutic (senolytics and senomorphics) compounds have been identified. In a recent study, we reported that gingerenone A (GinA) has a senolytic effect via mechanisms including the activation of caspase-3...

People constantly decide how much time to invest in rewarding activities. Foraging tasks assess this decision-making by measuring when individuals switch between contexts. People typically perform suboptimally in these tasks, largely due to overstaying, but it remains unclear whether this tendency changes with age independently of cognitive abilities and mental health factors. Previous research showing increased sensitivity to the opportunity cost of time in older adults predicts less...