Aging & Longevity
FcgammaR-targeted tuftsin clusters rejuvenate macrophages in preclinical sepsis-associated secondary infection
Sepsis-associated secondary infection often leads to a high mortality rate. Dysfunctional macrophages are primary contributors to inadequate antimicrobial defense in patients with sepsis-associated immunosuppression. Rejuvenating macrophage antibacterial capacity is beneficial for host defense against secondary infection. Here, we developed "BATMAN" (bacteria-targeted transformable macrophage nanorejuvenator), a self-assembling peptide nanoparticle to tackle sepsis-associated secondary infection...
Reconnecting the vagus nerve to the heart through nerve conduit preserves cardiac function in a minipig model of right cardiac vagotomy
The right vagus nerve is essential for cardiac homeostasis, and its intrathoracic resection can lead to postoperative cardiac complications. Strategies to restore vagal innervation after transection at the cardiac level remain lacking. Here, we show that early reconnection of the right vagus nerve using an implantable chitosan/poly-ε-caprolactone cuff-like nerve guidance conduit preserved cardiac mechanical function in adult male minipigs subjected to right cardiac vagotomy. Treated animals...
Distinct classes of gut bacterial molybdenum-dependent enzymes produce urolithins
Urolithin A is an anti-aging and anti-inflammatory gut bacterial metabolite derived from ellagic acid (EA), a polyphenol abundant in berries and nuts. The conversion of EA to urolithin A involves multiple chemically challenging phenol dehydroxylation steps that produce urolithins with varying bioactivities. Despite their biological and chemical significance, the bacterial enzymes responsible for urolithin production remain largely unidentified. Here, we use differential gene expression analysis,...
MASLD in the oldest-old: lack of association with cognition or functional autonomy and poor predictive utility of the hepatic steatosis index
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition increasingly recognized in aging populations. However, its clinical relevance in older adults-particularly in relation to sarcopenia, cognitive function, and rehabilitation outcomes-remains poorly defined. This retrospective observational study included in-patients admitted for geriatric rehabilitation in 2022 with available abdominal ultrasound. MASLD was defined according to AASLD/EASL criteria....
Facial skin aging: an integrative analysis of genetics, epigenetics, and lifestyle factors
Facial wrinkling is a prominent sign of aging, yet individuals exhibit unique trajectories of biological aging, contributing to the variability in facial appearance. Here, we present a pioneering study exploring the association between lifestyle choices, DNA methylation, and SNP genotypes with a range of facial skin aging phenotypes. The study demonstrated that age-related facial skin phenotypes are influenced by multiple environmental stressors. Epigenome-wide association analyses identified...
Structural marginalization of older adults within health care settings: a concept analysis
BACKGROUND AND OBJECTIVES: Ageing populations present new challenges for society, governments and for health systems. To accommodate the global demographic shift towards older populations, healthcare systems preparedness is of paramount importance. To prepare and equip health systems to best support older adults' health and well-being over the long-term it is necessary to understand how current systems may unintentionally marginalize older adults. Therefore, the purpose of this review and...
SUMO protease Pira induces autophagy-related cell death during Drosophila development
Autophagy is a major intracellular degradative process required for maintaining homeostasis in multicellular organisms. Aberrant autophagy is considered to induce internal environmental disturbance and cell death. Therefore, it is of great significance to explore the regulatory mechanism of autophagy. Here, we report a positive role of protein Pira, a SUMO protease, in inducing autophagy and autophagy-dependent cell death during Drosophila development. We found that overexpression of pira in...
The impact of neighborhood environment on physical activity among older adults: chain mediating roles of self-efficacy and outcome expectations
CONCLUSION: This study elucidates the underlying mechanisms between neighborhood environment and physical activity among older adults, Neighborhood environment is not only directly associated with physical activity levels among older adults but also indirectly influences physical activity through two psychological cognitive mediators: self-efficacy and outcome expectations.
A cohort study of growth differentiating factor - 15 (GDF-15) and Interleukin-6 (IL-6) as biomarkers of healthy aging in older adults living with HIV
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Single-cell RNA sequencing reveals a quiescence-senescence continuum and distinct senotypes following chemotherapy
Quiescence (reversible cell-cycle arrest) and senescence (irreversible arrest) are challenging to distinguish due to a lack of specific biomarkers, yet both arise simultaneously after chemotherapy. While senescence suppresses tumors by limiting proliferation and recruiting the immune system, quiescent cancer cells evade future therapies and may resume proliferation. Here, we pair time-lapse imaging of cell-cycle dynamics with single-cell RNA sequencing after etoposide treatment to differentiate...
Recommendations for biomarker data collection in clinical trials by longevity biotechnology companies
Biomarkers of aging have the potential to transform geroscience clinical trials because of their broad applications in stratifying participants, prioritizing interventions, and monitoring responses to geroprotectors. As longevity biotechnology companies (LBCs) continue to plan and launch innovative clinical trials, standard practices in collecting data and applying biomarkers of aging will allow the field to support parallel and ongoing validation and benchmarking efforts for aging biomarkers....
Synergistic effects of 3-O-methylquercetin and polyphenols on longevity, healthspan, and neuroprotection via FOXO/Nrf2
Polyphenols are emerging as promising candidates for promoting healthy aging and neuroprotection. Here, we investigated the effects of quercetin (Q), luteolin (L), and 3-O-methylquercetin (3OMQ), individually and in combination (FORM), on lifespan, healthspan, and neurobehavioral functions in Caenorhabditis elegans. Wild-type and mutant strains (including daf-2, daf-16, and skn-1) were exposed to the compounds, followed by assessments of longevity, motility, senescence biomarkers (lipofuscin and...
Promising Results With NAD Supplementation in Rare Diseases With Premature Aging and DNA Damage
Nicotinamide adenine dinucleotide (NAD) has garnered significant attention in recent years due to its central role in cellular metabolism and its potential as a supplement to promote health and longevity. While numerous human studies indicate that NAD supplementation offers benefits with minimal or no side effects, some studies show no observable advantages. This discrepancy highlights the importance of identifying individuals who are most likely to benefit from NAD-based interventions. One...
A single-cell atlas of the testicular interstitium defines Leydig progenitor networks sustaining Leydig cell homeostasis across the lifespan
Declining rates of male fertility pose a significant clinical challenge, while the mechanisms underlying testicular interstitial function remain incompletely understood. Here, we conducted a comprehensive analysis of the single-cell transcriptomic landscape of the murine testicular interstitium across the postnatal lifespan. The investigation unveiled a previously unrecognized population of Cd34^(+)/Sox4^(+) mesenchymal cells nestled within the interstitium, hinting at their potential as Leydig...
Preliminary Evidence for Increased Histone Succinylation as a Potential Epigenetic Marker for Longevity
Histone post-translational modifications (PTMs) are critical regulators of chromatin structure and gene expression, with broad implications for development, metabolism, and aging. While canonical modifications such as methylation and acetylation are well characterized, the role of histone succinylation remains poorly understood. Here, we investigated histone succinylation in the context of aging and exceptional longevity. Using mass spectrometry-based proteomics, we quantified histone...
Graded Calorie Restriction Causes Graded Slowing of Epigenetic Ageing in Mice
DNA methylation variation is associated with chronological ageing. Calorie restriction (CR) prolongs lifespan and healthspan in many species. Our hypothesis is that CR has an impact on DNA methylation patterns with increased CR leading to slower epigenetic ageing. We studied the effects of graded CR in male C57BL/6J mice on liver DNA methylation. Mice were fed ad libitum (AL) in the dark-phase or restricted by 10%, 20%, 30% or 40% from 5-months old for 19-months. Livers were collected in...
Senescent Cells Involved in Deterioration of Bone Microstructure by High-Frequency Parathyroid Hormone 1-34 Administration and Bone Loss
Osteoporosis is characterized by reduced bone mass and structural deterioration, leading to increased fracture risk, particularly in older adults. Parathyroid hormone (PTH) is a widely used anabolic therapy for osteoporosis; however, rapid bone loss after treatment discontinuation presents a significant clinical challenge. Cellular senescence has been implicated in age-related bone fragility. However, its role in PTH-induced bone remodeling and post-treatment bone loss remains unclear. This...
SenSeqNet: A Deep Learning Framework for Cellular Senescence Detection From Protein Sequences
Cellular senescence, defined as the irreversible arrest of cell proliferation in response to stress, contributes to tissue dysfunction and drives the progression of age-related diseases. Accurate detection of senescent states is therefore essential for understanding aging mechanisms and identifying therapeutic targets. However, conventional laboratory assays are time-consuming and difficult to scale. Here, we present SenSeqNet, a deep learning framework that predicts cellular senescence directly...
Mitochondrial DNA Variation in the Aging Human Cerebral Cortex and Cerebellum
Somatic differences in mitochondrial DNA (mtDNA) have been observed with aging and between brain regions for mutations, structural variation, and abundance, which are represented by single nucleotide variants (SNVs), large deletions, and copy number, respectively. We used bioinformatic methods to interrogate mtDNA changes and their relation to cortical and cerebellar aging using whole genome sequencing data from the North American Brain Expression Consortium. This dataset contained 292 unpaired...
A conceptual model of oxygen-ozone therapy as a modulator of aging via the HMGB1 pathway
CONCLUSION: OOT may potentially contribute to healthy aging by modulating redox adaptability. Its theoretical effectiveness is dose-dependent, with maximal benefit in aged or dysfunctional systems requiring reactivation of flexible stress responses. However, while the model offers insights into possible dynamic behaviours of the redox-inflammatory axis under ozone exposure, it is not yet calibrated to biological data and cannot predict real-world outcomes without further experimental support.
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