Aging & Longevity

Plasma proteomic aging clocks estimate biological age and are linked to age-related diseases, but thus far, there has been little focus on circulating extracellular matrix (ECM) proteins, which play a central role in tissue structure and age-related decline. Here, we use publicly available proteomic datasets to profile plasma ECM protein abundances across the human lifespan and reveal a distinct U-shaped trajectory with age. Our ECM-based aging clock, constructed from 14 plasma proteins,...

Middle-aged/older (MA/O) men with low testosterone have greater oxidative stress-mediated vascular endothelial dysfunction, a major risk factor for cardiovascular disease (CVD). Testosterone deficiency impairs mitochondria, a source and target of oxidative stress. Whether the greater vascular endothelial dysfunction in MA/O men with low testosterone is related to mitochondrial dysfunction is unknown. This cross-sectional study measured mitochondrial respiration in peripheral blood mononuclear...

Sarcopenia is characterized by age-related declines in muscle strength and mass, along with impaired physical function. It remains an unmet medical need, and there are no pharmacological interventions approved for this indication. The activation of growth hormone secretagogue receptor (GHSR)-1a, also known as ghrelin receptor, stimulates food intake and has acute anabolic effects. However, its impact on aging muscles remains uncertain. We examined the effects of GHSR-1a deletion on sarcopenia...

Immunosenescence drives organismal aging, yet quantifying its heterogeneity to uncover therapeutic targets remains challenging. We construct a human immune aging clock from single-cell multi-omics data of nearly 1.2 million human peripheral blood mononuclear cells from 230 individuals, precisely mapping immune aging. T cell (TC) transcriptomes are key predictors, revealing hallmarks such as naive cell loss and clonal contraction. This framework identifies the transcription factor RUNX1, whose...

Regulated cell death-processes such as apoptosis, pyroptosis, necroptosis, and ferroptosis-is essential for development, tissue homeostasis, and response to infection or cellular stress. The proteins involved in regulated cell death necessarily possess powerful and potentially damaging activities, including proteolysis, membrane pore formation, DNA cleavage, and inflammatory pathway activation. Traditionally, these activities drive cell death. However, sub-lethal activation of these pathways...

B cell development is one of the best-understood processes within the immune system. Coordination between transcriptional programs and antigen receptor assembly determines B cell fate, diversifies the antibody repertoire, and allocates specificities to the best-suited subsets. This enables B cells to respond to a wide variety of challenges, which, when encountered, can lead B cells to seemingly converge upon a common fate: the antibody-secreting plasma cell. Yet, as we discuss in this review,...

Gaining precise control of gene expression is crucial in biomedical applications. However, spatiotemporal precision remains challenging. Here, we present a remotely controlled in vivo gene switch responsive to electromagnetic fields (EMFs) that enables precise spatiotemporal activation of target genes. We uncovered the EMF-inducible gene switch activation mechanism via a CRISPR-Cas9 screen, identifying cytochrome b5 type B (Cyb5b) as an essential mediator likely acting as an EMF sensor. The...

CONCLUSION: This bibliometric survey defines the age and focus of the research into HGPS, with published research being highly concentrated and collaborative and showing possible future research directions in regenerative therapy and epigenetic control. Although the modern knowledge about the progeria condition has grown significantly, there is still a significant drawback of the psychosocial research, prolonged therapy trials, and equity in research participation globally. The results thus...

CONCLUSION: HIIT and plasma from young trained rats may offer protective or restorative benefits against sarcopenia. These findings highlight the therapeutic potential of combining or alternating exercise and plasma-based strategies in elderly populations.

Transfer RNA genes (tDNAs) are essential genomic elements that safeguard translational fidelity. Using the T2T version of the human genome we have mapped the position of human tDNAs and analyzed their individual transcriptional activities. Then we have characterized, at single base resolution, the impact of somatic mutations in human tDNAs and its relationship to the transcriptional status of each gene. We confirm that tDNAs are hotspots for somatic mutagenesis, and show that they display...

Given intractable challenges faced by practical sodium-ion batteries in safety, lifespan and broad temperature adaptability with synergistic interfacial compatibility, persistent efforts in electrolyte engineering are imperative to expedite their commercialization. Here we design a molecular anchoring electrolyte with flame retardancy, oxidative/reductive reliability and electrochemical durability against various electrodes. Through multiple dipolar interactions (δ^(+)H-δ^(-)F and...

Aging differentially affects disease risks of various organs¹. The endocrine organs undergo significant changes along aging. Clinical reports showed increased prevalence of thyroid disorders with age, especially hypothyroidism². Primary hypothyroidism includes congenital, autoimmune, and iatrogenic causes, which can occur throughout the lifespan. But those with unknown aetiology increase dramatically (~5 fold) in the elderly (≥75 years old)^(3,4). In thyrocytes, accumulated thyroglobulin...

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Ageing is characterised by the coupled decline of somatic and neural integrity. While the global burden of dementia continues to rise, scalable markers that capture this systemic vulnerability to identify individuals at risk remain scarce. Phase angle (PhA), a bioelectrical impedance analysis-derived metric reflecting cellular membrane integrity and body cell mass, has been linked to frailty and mortality; however, its potential as a sentinel for cognitive decline has not been systematically...

RAS family proteins, including HRAS, NRAS, and KRAS, are frequently mutated in cancer. Although there has been recent success in designing inhibitors that target oncogenic RAS, they elicit resistance and treating RAS-driven cancer remains difficult. Here, employing a proteomic analysis, we find that multiple spliceosome components are upregulated in the nuclei of cells undergoing RAS-induced senescence. This upregulation depends on RAS signalling and occurs in both senescent preneoplastic and...

Pancreatic islets maintain glucose homeostasis through coordinated action of endocrine and affiliate cell types and are central to type 2 diabetes (T2D) genetics and pathophysiology. Our understanding of robust human islet cell type-specific alterations in T2D remains limited. Here, we report comprehensive single-cell transcriptome profiling of 245,878 human islet cells from 48 donors spanning non-diabetic, pre-diabetic, and T2D states, and we identify 14 distinct cell types detected in every...

Whole-genome duplication (WGD) of diploid cells triggers various cell fates, such as cell death, cell cycle arrest, and proliferation with chromosome instability, contributing to broad bioprocesses, including differentiation, tumorigenesis, or aging. However, factors determining the post-WGD cell fates remain largely unknown. In this study, we found that cytokinesis failure (CF) and mitotic slippage (MS), two major routes of WGD induction, differentially affected post-WGD viability and...

The naked mole-rat (NMR) is a subterranean rodent known for its unique thermal biology, exceptional longevity, and resistance to cancer and hypoxia. However, its thermal biology remains controversial, with various reports describing NMRs as poikilotherms, heterotherms, mesotherms, or partial homeotherms. Here, we investigated whether the thermogenic potential of NMR brown adipose tissue and its UCP1 differ from those in mice and whether the lack of thermal insulation causes extreme changes in...

Monitoring molecular activities within single live cells is vital for understanding cellular differentiation, senescence, heterogeneity, and disease progression. However, conventional single-cell analyses often rely on micromanipulation or extraction followed by downstream measurements, which cannot capture in situ real-time dynamics. Fluorescent labeling and electrochemical methods provide temporal resolution but face limitations in labeling, substrate scope, and multiplexing. Here, we present...

Somatostatin/allatostatin C signaling regulates sleep, metabolism, memory, and longevity, but the underlying neuronal mechanisms remain unclear. We investigated the Caenorhabditis elegans somatostatin/allatostatin C ortholog NLP-99 and its receptor NPR-16. We found that the wake-active AIY neurons release NLP-99 to activate NPR-16. NPR-16 is G(i/o) coupled and acts cell nonautonomously to activate the sleep-active RIS neuron while acting autonomously in RIS to inhibit calcium activation and the...