Aging & Longevity

CONCLUSIONS: Like the broader frailty literature, emerging AI tools lack a consistent definition of frailty, leading to design and implementation inconsistencies. The absence of knowledge user involvement may further limit the clinical relevance and equity of these technologies.

The Interventions Testing Program (ITP) evaluated eleven compounds in genetically heterogeneous UM-HET3 mice to assess their potential to extend lifespan. These interventions included both novel agents and previously tested compounds administered at novel doses or starting ages. Despite prior evidence suggesting lifespan benefits of these proposed interventions in other models or under different conditions, none of the tested compounds significantly increased lifespan in male or female mice....

The human skin microbiome is essential for health and is shaped by both host and environmental factors. To establish a nationwide baseline, we profile the skin microbiome of 1,029 Chinese individuals across three body sites (hand, axilla, and foot), four geographic regions, and four ethnic groups using 16S rRNA gene sequencing. Within each skin site, we identify two cutotypes, one of which is consistently dominated by Staphylococcus. Microbial diversity and community composition vary across body...

Aging is a primary risk factor for disease progression in multiple sclerosis (MS). Because of this, treatments that can reduce the consequences of molecular aging, like senescence, have been proposed as a strategy to address disease progression. However, the effects of senolytics, a class of drugs which selectively ablate senescent cells, on the central nervous system are largely unknown. Here, we examined the effects of senolytic treatment on myelination and oligodendrocyte function in vivo...

Proteomics enables the systematic elucidation of biological mechanisms underlying frailty. Through a large proteome-wide association study of 2,911 plasma proteins from 50,506 UK Biobank participants, we identified 1,339 proteins significantly associated with frailty, highlighting collagen-containing extracellular matrix and vesicle lumen pathways. Replication in the TwinGene study confirmed partial but consistent associations. Mendelian randomization analyses identified five potentially causal...

We present TLPath, a deep learning framework that predicts bulk-tissue telomere length from tissue morphology extracted from routine histopathology images. The central thesis of TLPath is that telomere length can be determined from tissue morphology. Trained on >5,000 whole-slide images across 919 individuals and 18 organs, TLPath discovers that extracted morphological features naturally separate young, middle-aged, and elderly individuals, demonstrating that aging causes architectural changes...

Perovskite solar cells tend to degrade much faster under day-night cycling conditions. One key reason lies in the periodic strain in perovskite film under cycling mode due to its soft crystal lattice nature. Here, we propose a dynamic reversible crosslinking strategy by introducing disulfide-mediated cross-linkable additive of 2-methacryloyloxyethyl-thioctate. Combining with carbon-carbon double bond, 2-methacryloyloxyethyl-thioctate crosslinks at grain boundaries at high temperature through...

Cyclophosphamide (CTX) is a first-line chemotherapeutic agent for various cancers but is associated with a significant risk of ovarian dysfunction, which may even progress to premature ovarian failure (POF). Granulosa cell senescence is a key phenotypic manifestation of this process. Hydroxychloroquine (HCQ) exerts anti-senescence effects in age-related diseases; however, its efficacy in preventing CTX-induced ovarian damage remains elusive. We aimed to verify the protective effect of HCQ using...

Aging is a major risk factor for the onset and progression of many neurodegenerative diseases. Inflammation is the body's natural defense mechanism against harmful stimuli. A growing body of research has highlighted the intricate relationship between aging and inflammation, with chronic low-grade inflammation, often referred to as "inflammaging," being a hallmark of the aging process. Cycloneolitsol (CL) is a C-32 cycloartane-type triterpene from Taxodium ascendens which has been reported to...

The present study aimed to investigate the effect of obstructive sleep apnea (OSA) and its treatment with continuous positive airway pressure (CPAP), the gold standard treatment for OSA on changes of telomere length and its associated mechanisms. In this mechanistic pilot study of a selective patient population (middle-aged men, BMI < 35 kg/m², moderate-severe OSA), a 6-month randomized, double-blind, and sham-controlled clinical trial was conducted (Clinical Trials: NCT04872816, April 29, 2021...

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Glutathione (GSH) is an abundant antioxidant that protects against endogenous and exogenous toxic agents. The evidence over the relationship between GSH and cognitive integrity during aging is still scarce. In this study we investigated the relationship between GSH and cognitive integrity, cognitive effort and sustained cognitive effort. Second, we explored whether GSH modulation is related to other physiological properties such as blood oxygenation (BOLD response) and to brain excitability...

Aging is linked to a higher incidence of gut diseases such as inflammatory bowel disease (IBD), yet the underlying mechanisms remain unclear. We identified an age-related decline in magnesium (Mg) levels specifically in the gut across species, prompting investigation of its role in intestinal health. Functional studies demonstrated that Mg restriction accelerates gut aging in old but not in young mice and aggravates colitis severity. Multi-omics analysis of mouse tissues revealed that dietary Mg...

Cognitive decline during aging may be influenced by peripheral factors, including neuroproteins and pro-inflammatory cytokine levels, body composition, and physical fitness. However, the specific associations between these factors and cognitive performance remain underexplored. A comprehensive assessment, including peripheral cytokine and neuroprotein levels, body composition, physical performance (aerobic fitness and muscle strength), and cognitive function was performed in a cohort of 87 older...

In the absence of telomerase, telomere shortening triggers replicative senescence, a tumor suppressor mechanism that is also associated with oncogenic genomic instability. Yet, the precise mechanism that connects these seemingly opposing forces remains poorly understood. To directly study the complex interplay between senescence, telomere dynamics, and genomic instability, we develop a system in Saccharomyces cerevisiae to generate and track telomeres of precise length in the absence of...

The brain age gap (BAG) is defined as the difference between brain age estimated from MRI using artificial intelligence and chronological age, and has been proposed as a biomarker reflecting aging and neurodegeneration. However, the association between BAG and dementia-related biomarkers has yielded inconsistent findings in previous studies. Conventional training datasets have primarily been defined based on medical history and MRI findings, which may have included participants with underlying...

CONCLUSIONS: Dance serves as an effective nonpharmacological strategy for promoting healthy aging. Based on current evidence, public health policymakers should prioritize resource allocation toward the 70- to 75-year-old community-dwelling population. Regarding dance prescription design, we advocate for an 8-week baseline cycle to generate significant benefits and highlight the potential value of short-duration models (∼20 minutes) in enhancing adherence and improving function. However, given...

Alzheimer's disease (AD), an age-associated neurodegenerative disorder, is characterized by progressive cognitive decline, amyloid-β (Aβ) accumulation (including soluble oligomers and deposited aggregates), lipid dysregulation, and neuroinflammation. Although mutations in the amyloid precursor protein (APP) and accumulation of Aβ42 are established drivers of pathology, the mechanisms connecting oligomeric amyloid toxicity with lipid metabolism and inflammatory responses remain poorly understood....

Aging is an unavoidable part of life, but gaps still remain in the understanding of age-associated molecular changes within the brain. We generated single-nucleus multiome ATAC plus gene expression profiles in 357 human brain samples from European and African admixed ancestry individuals ranging from 15 to 100 years old. The final dataset consisted of paired transcriptomic and epigenomic profiles for over 1.5 million cells. These were classified into seven major cell types using canonical marker...