Aging & Longevity

High pressure can create extreme conditions that enable the formation of novel materials and the discovery of new phenomena. However, the ability to preserve the desirable characteristics of materials obtained under high pressure has remained an elusive challenge, as the pressure-induced changes are typically reversible, except for the pressure-induced chemical reactions such as polymerization of hydrocarbons. Here, we propose the concept of "pressure aging" (PA) that enables the permanent...

Many aspects of inflammation increase with aging in mice and humans. Transcriptomic analysis revealed that many murine anti-aging interventions produce lower levels of pro-inflammatory proteins. Here, we explore the hypothesis that different longevity interventions diminish NF-κB levels, potentially mediating some of the anti-inflammatory benefits of lifespan-extending interventions. We found that the NF-κB protein p65 is significantly downregulated in the liver of several kinds of slow-aging...

The global aging population raises concerns about heart failure (HF), yet its association with accelerated biological age (BA) remains inadequately understood. We aimed to examine the longitudinal association between BA acceleration and incident HF risk, assess its modifying effect on genetic susceptibility, and how much BA acceleration mediates the impact of modifiable health behaviors on incident HF. We analyzed 274,608 UK Biobank participants without HF at baseline. Two BA accelerations...

This study aims to investigate the association between metabolomic aging acceleration and body mass index (BMI) phenotypes with mortality and obesity-related morbidities (ORMs). 85,458 participants were included from the UK Biobank. Metabolomic age was determined using 168 metabolites. The Chronological Age-Adjusted Gap was used to define metabolomically younger (MY) or older (MO) status. BMI categories were defined as normal weight, overweight, and obese. Participants were categorized into MY...

INTRODUCTION: During aging, many cellular processes, such as autophagic clearance, DNA repair, mitochondrial health, metabolism, nicotinamide adenine dinucleotide (NAD+) levels, and immunological responses, become compromised. Urolithin A (UA) and Nicotinamide Riboside (NR) are two naturally occurring compounds known for their anti-inflammatory and mitochondrial protective properties, yet the effects of these natural substances on microglia cells have not been thoroughly investigated. As both UA...

CONCLUSION: There is a correlation between sarcopenia and cognitive function, individuals with sarcopenia performing poorly in overall cognition as well as refined dimensions. The degree of cognition like fluency degenerates over time with increasing severity of sarcopenia.

Adult stem cells maintain homeostasis and enable regeneration of most tissues. Quiescence, proliferation, and differentiation of stem cells and their progenitors are tightly regulated processes governed by dynamic transcriptional, epigenetic, and metabolic programs. Previously thought to merely reflect a cell's energy state, metabolism is now recognized for its critical regulatory functions, controlling not only energy and biomass production but also the cell's transcriptome and epigenome. In...

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Hypoxia enhances histone methylation by inhibiting oxygen- and α-ketoglutarate-dependent demethylases, resulting in increased methylated histones. This study reveals how hypoxia-induced methylation affects histone clipping and the reorganization of heterochromatin into senescence-associated heterochromatin foci (SAHF) during oncogene-induced senescence (OIS) in IMR90 human fibroblasts. Notably, using top-down proteomics, we discovered specific cleavage sites targeted by Cathepsin L (CTSL) in H3,...

While previous research has demonstrated the therapeutic efficacy of telomerase reverse transcriptase (TERT) overexpression using adeno-associated virus and cytomegalovirus vectors to combat aging, the broader implications of TERT germline gene editing on the mammalian genome, proteomic composition, phenotypes, lifespan extension, and damage repair remain largely unexplored. In this study, we elucidate the functional properties of transgenic mice carrying the Tert transgene, guided by precise...

Cardiomyocyte (CM) nuclei are constantly exposed to mechanical stress, but how they maintain their nuclear shape remains unknown. In this study, we found that ventricular CM nuclei acquire characteristic prominent spatial organizations of heterochromatin (SOH), which are disrupted by high-level expression of H2B-mCherry in mice. SOH disruption was associated with nuclear softening, leading to extreme elongation and rupture under unidirectional mechanical stress. Loosened chromatin then leaks...

Alzheimer's disease (AD) is an aging-related neurodegenerative disorder that results in progressively impaired memory and is often associated with amyloid plaques. Previous studies implicate the deacetylases SIRT1 and SIRT2 in regulating the processing of amyloid precursor protein (APP). Here, we investigated whether APP is regulated by the related deacetylase SIRT6, which shows aging-associated decreases in activity. We found that the abundance of SIRT6 was reduced in the cortex and hippocampus...

In a comprehensive study to decipher the multi-layered response to the chemotherapeutic agent temozolomide (TMZ), we analyzed 427 genomes and determined mutational patterns in a collection of ∼40 isogenic DNA repair-deficient human TK6 lymphoblast cell lines. We first demonstrate that the spontaneous mutational background is very similar to the aging-associated mutational signature SBS40 and mainly caused by polymerase zeta-mediated translesion synthesis (TLS). MSH2-/- mismatch repair (MMR)...

Metaxins are a family of evolutionarily conserved proteins that reside on the mitochondria outer membrane (MOM) and participate in the protein import into the mitochondria. Metaxin-2 (Mtx2), a member of this family, has been identified as a key component in the machinery for mitochondrial transport in both C. elegans and human neurons. To deepen our understanding of Mtx2's role in neurons, we examined the homologous genes CG5662 and CG8004 in Drosophila. The CG5662 is a non-essential gene while...

Chronological age is a crucial risk factor for diseases and disabilities among older adults. However, individuals of the same chronological age often exhibit divergent biological aging states, resulting in distinct individual risk profiles. Chronological age estimators based on omics data and machine learning techniques, known as aging clocks, provide a valuable framework for interpreting molecular-level biological aging. Metabolomics is an intriguing and rapidly growing field of study,...

Aging-associated cardiac hypertrophy (AACH) increases susceptibility to heart failure in the elderly. Chromatin remodeling contributes to the gene reprogramming in AACH; however, the intrinsic regulations remain elusive. We performed a transcriptome analysis for AACH in comparison with pressure-overload-induced pathological cardiac hypertrophy in mice and identified myeloid leukemia factor 1 (MLF1) as an aging-sensitive factor whose expression was reduced during aging but could be reversed by...

Double-strand breaks (DSBs) are a formidable threat to genome integrity, potentially leading to cancer and various genetic diseases. The prolonged lifespan of mammalian oocytes increases their susceptibility to DNA damage over time. While somatic cells suppress DSB repair during mitosis, oocytes exhibit a remarkable capacity to repair DSBs during meiotic maturation. However, the precise mechanisms underlying DSB repair in oocytes remain poorly understood. Here, we describe the pivotal role of...

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Cellular senescence is an aging mechanism characterized by cell cycle arrest and a senescence-associated secretory phenotype (SASP). Preclinical studies demonstrate that senolytic drugs, which target survival pathways in senescent cells, can counteract age-associated conditions that span several organs. The comparative efficacy of distinct senolytic drugs for modifying aging and senescence biomarkers in vivo has not been demonstrated. Here, we established aging- and senescence-related plasma...

Carotenoids are naturally occurring pigments found in plants and certain microorganisms. Some carotenoids act as precursors to vitamin A, which is essential for various health aspects, including vision, immune function, and skin health. Carotenoids, including α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin, are known to reduce the risk of age-related diseases and promote healthy aging. This study examines the relationship between dietary carotenoid levels and biological...