Aging & Longevity

Subjective well-being (SWB) is often described as being U-shaped over adulthood, declining to a midlife slump and then improving thereafter. Improved SWB in later adulthood has been considered a paradox given age-related declines in health and social losses. While SWB has mostly been studied in high-income countries, it remains largely unexplored in rural subsistence populations lacking formal institutions that reliably promote social welfare. Here, we evaluate the age profile of SWB among three...

Cellular senescence, traditionally associated with aging and chronic diseases, has recently been identified as a potential facilitator of tissue regeneration via a senescence-associated secretory phenotype (SASP). In rodents, the meniscus is known to regenerate spontaneously from the surrounding synovium, but the mechanism, and especially its relationship to cellular senescence, remains unclear. This study investigated the contribution of cellular senescence to spontaneous repair of the rat...

Senescent neural progenitor cells have been identified in brain lesions of people with progressive multiple sclerosis (PMS). However, their role in disease pathobiology and contribution to the lesion environment remains unclear. By establishing directly induced neural stem/progenitor cell (iNSC) lines from PMS patient fibroblasts, we studied their senescent phenotype in vitro. Senescence was strongly associated with inflammatory signaling, hypermetabolism, and the senescence-associated secretory...

Cellular senescence is a permanent cell growth arrest that occurs in response to various intrinsic and extrinsic stimuli and is associated with cellular and molecular changes. Long non-coding RNAs (lncRNAs) are key regulators of cellular senescence by affecting the expression of many important genes involved in senescence-associated pathways and processes. Here, we evaluated a panel of lncRNAs associated with senescence for their differential expression between young and senescent human dermal...

Age-related changes in oligodendrocyte precursor cells (OPCs) contribute to white matter dysfunction. In aged mice, we hypothesized that myelin-dense fimbria OPCs possess niche-specific properties, compared to hippocampal OPCs. Aged fimbria OPCs were fewer, larger, and localized to neighboring microglia. We identified age-increased p16/Cdkn2a-expressing OPCs enriched for senescence-related pathways and distinct senescence signatures between hippocampus and fimbria. Aged brain OPC populations...

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tRNAs are evolutionarily ancient molecular decoders essential for protein translation. In eukaryotes, tRNAs and other short, noncoding RNAs are transcribed by RNA polymerase (Pol) III, an enzyme that promotes ageing in yeast, worms, and flies. Here, we show that a partial reduction in Pol III activity specifically disrupts tRNA levels. This effect is conserved across worms, flies, and mice, where computational models indicate that it impacts mRNA decoding. In all 3 species, reduced Pol III...

OBJECTIVE: Most older adults in the United States (U.S.) prefer to remain in their current housing as they age, but difficulty with mobility (e.g., walking) may make this more challenging. We estimated the association between difficulty with mobility (mobility) and residential relocation in the following year.

Greater perceived physical fatigability and lower skeletal muscle energetics are both predictors of mobility decline. Characterizing associations between muscle energetics and perceived fatigability may provide insight into potential targets to prevent mobility decline. We examined associations of in vivo (maximal ATP production, ATPmax) and ex vivo (maximal carbohydrate supported oxidative phosphorylation [max OXPHOS] and maximal fatty acid supported OXPHOS [max FAO OXPHOS]) measures of...

Defective glucose-stimulated insulin secretion (GSIS) and β-cell senescence are hallmarks in diabetes. The mitochondrial enzyme pyruvate carboxylase (PC) has been shown to promote GSIS and β-cell proliferation in the clonal β-cell lines, yet its physiological relevance remains unknown. Here, we provide animal and human data showing a role of PC in protecting β-cells against senescence and maintaining GSIS under different physiological and pathological conditions. β-cell-specific deletion of PC...

Chronic inflammation with progressive age, called inflammaging, contributes to the pathogenesis of cardiovascular diseases. Previously, we have shown increased vascular expression of the Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in aged mice and humans, presumably via mutual upregulation with the pro-inflammatory cytokine TNF-α. CEACAM1 is critical for aging-associated vascular alterations like endothelial dysfunction, fibrosis, oxidative stress, and sustained...

CONCLUSIONS: This study highlights a sex-specific association of inflammation in the mechanisms of hyperphosphatemia-related muscle weakness. The findings emphasize the importance of managing both hyperphosphatemia and chronic inflammation to mitigate their collective impact on muscle function, particularly in older men. Addressing these factors is crucial for promoting muscle health in later life.

We explored the intricate quantitative structure of household food waste and their corresponding life cycle greenhouse gas emissions from raw materials to retail utilizing a combination of household- and food-related economic statistics and life cycle assessment in Japan. Given Japan's status as a nation heavily impacted by an aging population, this study estimates these indicators for the six age brackets of Japanese households, showing that per capita food waste increases as the age of the...

Alzheimer's disease (AD) presents a growing societal challenge, driven by an aging population. It is characterized by neurodegeneration linked to β-amyloid (Aβ) and tau protein aggregation. Reactive glial cell-mediated neuroinflammation exacerbates disease progression by facilitating the accumulation of Aβ and impairing its clearance, thus highlighting potential therapeutic targets. Aerial parts of Artemisia iwayomogi (AIH), a kind of mugwort, has been consumed as a medicinal herb in East Asia...

Sirtuin 6 (SIRT6) has many functions, but its most notable contribution lies in the intricate regulation of cell senescence and lifespan. The effect of the SIRT6 gene on body size and longevity in dogs has not been extensively studied, particularly with regard to alternative splicing mechanisms. To address this gap, the present study used a comprehensive approach that integrated bioinformatics analysis, DNA sequence analysis, and next-generation sequencing-based targeted sequencing analyses. Our...

Arterial thrombosis is a leading cause of death and disability worldwide with no effective bioassay for clinical prediction. As a symbolic feature of arterial thrombosis, severe stenosis in the blood vessel creates a high-shear, high-gradient flow environment that facilitates platelet aggregation towards vessel occlusion. Here, we present a thrombus profiling assay that monitors the multi-dimensional attributes of thrombi forming in such biomechanical conditions. Using this assay, we demonstrate...

Caloric restriction (CR) can extend the organism life- and health-span by improving glucose homeostasis. How CR affects the structure-function of pancreatic beta cells remains unknown. We used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis reveal that CR activates transcription factors important for beta cell identity and homeostasis, while imaging...

Cellular senescence has been implicated in many age-related pathologies including atherosclerosis, heart failure, age-related cardiac remodeling, diabetic cardiomyopathy and the metabolic syndrome. Here, we will review the characteristics of senescent cells and their endogenous regulators, and summarize the metabolic stressors that induce cell senescence. We will discuss the evidence of cell senescence in the onset and progression of several cardiometabolic diseases and the therapeutic potential...

Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of...