Aging & Longevity

The thymus is the central organ where T cells differentiate and proliferate. T cells experience the TCR recombination to generate diversity, self-antigen tolerance, and immune response. However, the spatial heterogeneity of transcriptomics and immune repertoire of the thymus during aging haven't been studied. We constructed the thymus's spatial transcriptomics and spatial immune repertoire atlas by TCR-specific amplification. The integrated multi-omics analysis of the scRNA-seq, ST-seq,...

The gut mycobiome plays an essential role in human health, yet its influence on the progression of arterial stiffness, a key feature of vascular aging, remains obscure. In this study, we aimed to investigate the involvement of intestinal fungi in the exacerbation of arterial stiffness. In total, 763 participants were invited for the brachial-ankle pulse wave velocity test to determine their status of arterial stiffness. The gut mycobiome was identified through internal transcribed spacer...

CONCLUSIONS: Female sex and physical activity were associated with lower physiological dysregulation, whereas higher BMI was associated with greater dysregulation. These findings underscore the importance of sex differences and modifiable lifestyle factors, particularly physical activity and adiposity in multisystem physiological burden among older US adults.

Age is a major risk factor for cardiovascular disease, yet the molecular mechanisms underlying human cardiac aging are not fully understood. Using bulk RNA sequencing data from the Genotype-Tissue Expression (GTEx) project, we identified cardiac age-associated genes by intersecting transcripts significantly correlated with age in both the atrial appendage and left ventricle, while excluding those similarly altered in skeletal muscle. Among these, 131 genes were positively correlated with age,...

Satellite cells (SCs) are essential for skeletal muscle regeneration, but their function declines with aging, often associated with increased pro-apoptotic signaling. This study investigated the impact of in vitro serum starvation-as a model of acute microenvironmental and nutrient stress-on the apoptosis and differentiation potential of human SCs from young and aged donors. SCs were isolated from the Vastus Lateralis of young and aged subjects and cultured in serum-free medium for up to 72 h....

We examined whether a genome-wide polygenic lifespan score (PLS) is associated with all-cause mortality and how this association compares with associations between long-term lifestyle factors and mortality. The PLS was computed for the older Finnish Twin Cohort (mean age 57.4 years; 45.2% men; N = 5575). Cox regression was used to estimate the effects of the PLS on all-cause mortality risk, before and after adding sex, physical activity, BMI, alcohol consumption, smoking behavior, and education...

Genotype-first screening compares patient genomes to a standard reference. The GRCh38 linear assembly contains reference minor alleles (RMAs), posing a critical structural vulnerability for automated clinical variant classification. To determine whether RMAs systematically generate false-positive annotations, we conducted an observational case series of 20 healthy adults undergoing preventive genome sequencing. Automated bioinformatic processing was performed using the GRCh38 linear reference to...

Falls in older adults are a significant public health concern. Action simulation interventions involving action observation and/or motor imagery have been proposed as alternative or adjunct strategies to physical exercise for reducing fall risk. These approaches may minimize barriers to physical practice and may specifically target deficits in motor planning that are linked to falls. The purpose of this scoping review is to examine how action simulation interventions have been applied and...

CONCLUSIONS: SIRT3 deficiency promotes age-related vascular impairment potentially by mediating EndMT and mitochondrial dysfunction, Thus, SIRT3 represents a potential therapeutic target for delaying vascular aging and associated cardiovascular diseases.

Mitochondrial reactive oxygen species (mtROS) have been implicated in aging and disease for decades and are typically viewed as a unitary, non-specific oxidative burden on cells and tissues. However, recent studies have identified at least eleven individual sources of mitochondrial ROS (ISOMRs) and revealed that ISOMRs have distinct, dynamic, and often reversible roles in diverse physiological and pathological processes, including neurodegenerative diseases, immune and metabolic dysregulation,...

Cellular senescence is a central driver of organismal ageing and related pathologies, primarily promoting chronic inflammation and tissue dysfunction through the senescence-associated secretory phenotype (SASP). Unlike senolytics, which aim to eliminate senescent cells, senomorphic agents offer a complementary therapeutic strategy by modulating the SASP without clearing the cells, thereby preserving their potential physiological functions. This review systematically elucidates the multi-target...

Endometriosis (EMs) is characterized by chronic pelvic inflammation, but the etiology of this inflammation remains poorly understood. The senescence-associated secretory phenotype (SASP), whereby senescent cells secrete pro-inflammatory cytokines, is a potential mechanism. This study investigates the pro-inflammatory SASP in EMs and its underlying influences. Through molecular assays and single-cell RNA-seq analysis, we found a subgroup of endometrial stromal cells (ESCs) marked by SASP in both...

T follicular helper (T(FH)) cells support B cell function by promoting memory B cell differentiation and sustaining long-lasting antibody responses, thereby enabling immunity that protects the host from subsequent infections. T(FH) cells are essential for orchestrating the antibody-mediated immunity achieved via vaccination, which has had a profound global impact in reducing the morbidity and mortality associated with infectious diseases. T(FH) cells provide help to B cells both within and...

Dietary protein is a key regulator of metabolic health in humans and rodents. Many of the benefits of protein restriction are mediated by reduced intake of dietary branched-chain amino acids (leucine, valine and isoleucine) and restriction of the branched-chain amino acids is sufficient to extend healthspan and lifespan in mice. Here we find that valine restriction (Val-R) improves metabolic health in C57BL/6J mice, promotes leanness and glycemic control across ages, and reduces frailty, cancer...

Posttraumatic stress disorder (PTSD) is associated with accelerated cognitive aging and increased risk for Alzheimer's disease (AD) and related dementias (ADRD), yet the biological substrates linking trauma-related psychiatric illness to altered brain aging trajectories remain poorly defined. The basolateral amygdala plays a central role in threat processing and emotional memory and exhibits persistent hyperactivity in PTSD, but its molecular and pathological state in aging individuals with PTSD...

Macroautophagy/autophagy is a well-established homeostatic mechanism that contributes to the integrity of multiple regulatory biological activities including but not limited to the gastro-intestinal tract and cognitive integrity. Autophagy also plays a central role in tissue regeneration, metamorphosis and development whereas defects in autophagy are associated with a wide range of disorders including metabolic diseases such as diabetes, organ pathophysiologies including liver, lung and heart...

Age-related endothelial dysfunction in the cerebral microcirculation contributes significantly to the pathogenesis of vascular cognitive impairment and dementia (VCID). Time-restricted eating (TRE) has emerged as a promising lifestyle intervention with beneficial effects on metabolic and vascular health; however, the mechanisms by which TRE influences the brain microvasculature remain incompletely understood. In particular, the role of circulating factors induced by TRE in modulating endothelial...

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Tendinopathy is a common condition that causes long-term pain. The inflammatory microenvironment (inflamed soil) promotes the ingrowth of sensory nerves (a key pain trigger) and induces functional impairments in tendon stem/progenitor cells (TSPCs) (dysfunctional seeds). These interconnected processes collectively drive the progression of tendinopathy, which is frequently accompanied by persistent pain. Here, we develop a multifunctional nanoplatform (MSM-DTM) by integrating macrophage-sensory...

Skeletal muscle aging is a complex biological process that involves coordinated changes in multiple cell types. Recent breakthroughs in single-cell sequencing technology have provided new perspectives regarding this process. Here, we systematically summarize current progress in single-cell technology with respect to skeletal muscle aging. We focused on specific molecular characteristics and interaction networks of muscle fiber, satellite and immune cells during aging. Aging skeletal muscles...