Aging & Longevity

Age-related increases in cerebral pulsatility are thought to stress cerebral microcirculation, with effects that may vary across different brain regions. The aging brain also undergoes neurofunctional changes to preserve and, in some cases, enhance cognitive abilities. This study investigated the association between cerebral pulsatility and neurofunctional changes in aging. Sixty healthy adults were divided into two groups of younger (aged 19-31 years) and older adults (aged 62-75 years)....

Hippocampal adult neural stem cells (NSCs) contribute to neurogenesis and astrogliogenesis throughout life. They play multifaceted roles in hippocampal function, including memory processing, stress regulation, and cognitive flexibility. Located in unique neurogenic niches like the subgranular zone of the hippocampal dentate gyrus, NSCs exhibit notable heterogeneity and can be classified into quiescent, activated, and intermediate transitioning states. This diversity, while instrumental to their...

The human kidney maintains homeostasis through a complex network of up to a million nephrons, its fundamental tissue units. Using innovative tissue processing and light sheet fluorescence microscopy, we mapped the 3D neurovascular connectivity of nephrons to understand how their structural organization enables coordinated functions like filtration, absorption, and blood pressure regulation. Our analysis revealed developmental changes in glomerular orientation, density, volume, and innervation...

Neural stem cells (NSCs) in the mammalian brain decline rapidly with age, leading to impairment of hippocampal memory function in later life. However, the relationship between epigenetic remodeling and transcriptional regulation that compromises hippocampal NSC activity during the early stage of chronological aging remains unclear. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) on NSCs and newly generated neurons across different stages....

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Caloric restriction and methionine restriction-driven enhanced lifespan and healthspan induces 'browning' of white adipose tissue, a metabolic response that increases heat production to defend core body temperature. However, how specific dietary amino acids control adipose thermogenesis is unknown. Here, we identified that weight loss induced by caloric restriction in humans reduces thiol-containing sulfur amino acid cysteine in white adipose tissue. Systemic cysteine depletion in mice causes...

Reactive thiols of proteinaceous cysteines are vital to cell biology by serving as sensor, effector and buffer of environmental redox fluctuations. Being the major source, as well as the prime target, of reactive oxygen species (ROS), mitochondria confront great challenges in preserving their thiol pool. Here we show that ROS modulator 1 (ROMO1), a small inner mitochondrial membrane protein, plays a role in protecting the mitochondrial cysteinome. ROMO1 is redox sensitive and reactive and...

Cellular senescence increases with age and contributes to age-related declines and pathologies. We identified circulating biomarkers of senescence and related them to clinical traits in humans to facilitate future noninvasive assessment of individual senescence burden, and efficacy testing of novel senotherapeutics. Using a nanoparticle-based proteomic workflow, we profiled the senescence-associated secretory phenotype (SASP) in THP-1 monocytes and examined these proteins in 1,060 plasma samples...

Aging alters morphology and locomotor function in diverse organisms, yet standardized model systems for studying these changes remain limited to a relatively few species. Here, we present a comprehensive analysis of age- and sex-dependent morphological variations in house crickets (Acheta domesticus), integrating refined husbandry protocols to enhance reproducibility and translational relevance. To ensure data consistency, we implemented a standardized husbandry framework incorporating...

Werner syndrome (WS) is a rare hereditary progeroid syndrome caused by mutations in the WRN gene. Patients frequently develop various age-associated diseases prematurely, often leading to early mortality (≤ 60 years of age). Depletion of nicotinamide adenine dinucleotide (NAD)^(+) has been reported in patients with WS, suggesting a key role in the pathogenesis of WS. NAD^(+) supplementation may improve the condition of WS and other accelerated aging diseases. Therefore, we conducted a...

Resilience is increasingly recognized as a central factor in how older adults adapt to life's inevitable changes, yet many clinicians remain unfamiliar with its practical applications in late life. Drawing on the true story of Cocota, a Brazilian matriarch who lived to be 100, this special article illustrates how resilience is neither a static trait nor limited to mere survival. Instead, it emerges over decades, shaped by early adversities and sustained through purposeful roles, strong social...

This research paper investigates the prevalence of functional limitations among employed adults in the United States and the association between these limitations and medical conditions. The authors administered a survey adapted from the Dutch Functional Abilities List to a nationally representative sample of US adults ages 22 and older, finding that nearly three-quarters of working adults report at least one functional limitation, with an average of nearly six functional limitations per working...

Emerging evidence suggests that creatine, a naturally occurring amino acid derivative and conditionally essential nutrient, may modulate cellular senescence through mechanisms such as enhancing cellular energy homeostasis, mitigating oxidative stress, and influencing key signaling pathways implicated in aging processes. This review critically evaluates the current body of research, highlights existing gaps in the mechanistic understanding, and emphasizes the importance of targeted studies to...

CONCLUSIONS: The changes in end-of-life care models for Chinese older adults are influenced by both age and period effects. The sustainability of the child-centered care model, influenced by filial piety culture, is facing challenges, as the responsibility for end-of-life care has gradually expanded from children to a broader circle of caregivers. Future efforts should focus on developing a care model based on family caregiving, supplemented by formal care services. Additionally, older women and...

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...