Aging & Longevity

The p21CIP1-CDK4-DREAM axis is a master regulator of genotoxic stress-induced cellular senescence

1 day 13 hours ago
Cellular senescence, a major driver of aging, can be stimulated by DNA damage, and is counteracted by the DNA repair machinery. Here we show that in p16INK4a-deficient cells, senescence induction by the environmental genotoxin B[a]P or ionizing radiation (IR) completely depends on p21CIP1. Immunoprecipitation-based mass spectrometry interactomics data revealed that during senescence induction and maintenance, p21CIP1 specifically inhibits CDK4 and thereby activates the DREAM complex. Genome-wide...
Ariane Schmidt

Adding intrinsically disordered proteins to biological ageing clocks

1 day 13 hours ago
Research into how the young and old differ, and which biomarkers reflect the diverse biological processes underlying ageing, is a current and fast-growing field. Biological clocks provide a means to evaluate whether a molecule, cell, tissue or even an entire organism is old or young. Here we summarize established and emerging molecular clocks as timepieces. We emphasize that intrinsically disordered proteins (IDPs) tend to transform into a β-sheet-rich aggregated state and accumulate in...
Dorothee Dormann

Adipose tissue as a linchpin of organismal ageing

1 day 13 hours ago
Ageing is a conserved biological process, modulated by intrinsic and extrinsic factors, that leads to changes in life expectancy. In humans, ageing is characterized by greatly increased prevalence of cardiometabolic disease, type 2 diabetes and disorders associated with impaired immune surveillance. Adipose tissue displays species-conserved, temporal changes with ageing, including redistribution from peripheral to central depots, loss of thermogenic capacity and expansion within the bone marrow....
Tammy T Nguyen

CISD3/MiNT is required for complex I function, mitochondrial integrity, and skeletal muscle maintenance

1 day 13 hours ago
Mitochondria play a central role in muscle metabolism and function. A unique family of iron-sulfur proteins, termed CDGSH Iron Sulfur Domain-containing (CISD/NEET) proteins, support mitochondrial function in skeletal muscles. The abundance of these proteins declines during aging leading to muscle degeneration. Although the function of the outer mitochondrial CISD/NEET proteins, CISD1/mitoNEET and CISD2/NAF-1, has been defined in skeletal muscle cells, the role of the inner mitochondrial CISD...
Rachel Nechushtai

Single-cell genomics and regulatory networks for 388 human brains

1 day 13 hours ago
Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics datasets into a resource comprising >2.8 million nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified...
Prashant S Emani

Nrf2 activation by pyrroloquinoline quinone inhibits natural aging-related intervertebral disk degeneration in mice

1 day 13 hours ago
Age-related intervertebral disk degeneration (IVDD) involves increased oxidative damage, cellular senescence, and matrix degradation. Pyrroloquinoline quinone (PQQ) is a water-soluble vitamin-like compound with strong anti-oxidant capacity. The goal of this study was to determine whether PQQ can prevent aging-related IVDD, and the underlying mechanism. Here, we found that dietary PQQ supplementation for 12 months alleviated IVDD phenotypes in aged mice, including increased disk height index and...
Qi Xue

Past, present, and future of cell replacement therapy for parkinson's disease: a novel emphasis on host immune responses

2 days 13 hours ago
Parkinson's disease (PD) stands as the second most common neurodegenerative disorder after Alzheimer's disease, and its prevalence continues to rise with the aging global population. Central to the pathophysiology of PD is the specific degeneration of midbrain dopamine neurons (mDANs) in the substantia nigra. Consequently, cell replacement therapy (CRT) has emerged as a promising treatment approach, initially supported by various open-label clinical studies employing fetal ventral mesencephalic...
Tae-Yoon Park

Aging impairs cold-induced beige adipogenesis and adipocyte metabolic reprogramming

2 days 13 hours ago
The energy-burning capability of beige adipose tissue is a potential therapeutic tool for reducing obesity and metabolic disease, but this capacity is decreased by aging. Here, we evaluate the impact of aging on the profile and activity of adipocyte stem and progenitor cells (ASPCs) and adipocytes during the beiging process in mice. We found that aging increases the expression of Cd9 and other fibro-inflammatory genes in fibroblastic ASPCs and blocks their differentiation into beige adipocytes....
Corey D Holman

Highly reversible zinc metal anode enabled by strong Brønsted acid and hydrophobic interfacial chemistry

3 days 13 hours ago
Uncontrollable zinc (Zn) plating and hydrogen evolution greatly undermine Zn anode reversibility. Previous electrolyte designs focus on suppressing H(2)O reactivity, however, the accumulation of alkaline byproducts during battery calendar aging and cycling still deteriorates the battery performance. Here, we present a direct strategy to tackle such problems using a strong Brønsted acid, bis(trifluoromethanesulfonyl)imide (HTFSI), as the electrolyte additive. This approach reformulates battery...
Qingshun Nian

Investigating nutrient biomarkers of healthy brain aging: a multimodal brain imaging study

3 days 13 hours ago
The emerging field of Nutritional Cognitive Neuroscience aims to uncover specific foods and nutrients that promote healthy brain aging. Central to this effort is the discovery of nutrient profiles that can be targeted in nutritional interventions designed to promote brain health with respect to multimodal neuroimaging measures of brain structure, function, and metabolism. The present study therefore conducted one of the largest and most comprehensive nutrient biomarker studies examining...
Christopher E Zwilling

SDHAF1 confers metabolic resilience to aging hematopoietic stem cells by promoting mitochondrial ATP production

3 days 13 hours ago
Aging generally predisposes stem cells to functional decline, impairing tissue homeostasis. Here, we report that hematopoietic stem cells (HSCs) acquire metabolic resilience that promotes cell survival. High-resolution real-time ATP analysis with glucose tracing and metabolic flux analysis revealed that old HSCs reprogram their metabolism to activate the pentose phosphate pathway (PPP), becoming more resistant to oxidative stress and less dependent on glycolytic ATP production at steady state....
Shintaro Watanuki

Locus coeruleus integrity is related to an exploitation-based decision-making bias in older adulthood

3 days 13 hours ago
Optimal decision-making balances exploration for new information against exploitation of known rewards, a process mediated by the locus coeruleus and its norepinephrine projections. We predicted that an exploitation-bias that emerges in older adulthood would be associated with lower microstructural integrity of the locus coeruleus. Leveraging in vivo histological methods from quantitative MRI-magnetic transfer saturation-we provide evidence that older age is associated with lower locus coeruleus...
Gary R Turner

Increased ANKRD1 Levels in Early Senescence Mediated by RBMS1-Elicited ANKRD1 mRNA Stabilization

3 days 13 hours ago
Cellular senescence is a dynamic biological process triggered by sublethal cell damage and driven by specific changes in gene expression programs. We recently identified ANKRD1 (ankyrin repeat domain 1) as a protein strongly elevated after triggering senescence in fibroblasts. Here, we set out to investigate the mechanisms driving the elevated production of ANKRD1 in the early stages of senescence. Our results indicated that the rise in ANKRD1 levels after triggering senescence using etoposide...
Chang Hoon Shin

Tho2-mediated escort of Nrd1 regulates the expression of aging-related genes

3 days 13 hours ago
The relationship between aging and RNA biogenesis and trafficking is attracting growing interest, yet the precise mechanisms are unknown. The THO complex is crucial for mRNA cotranscriptional maturation and export. Herein, we report that the THO complex is closely linked to the regulation of lifespan. Deficiencies in Hpr1 and Tho2, components of the THO complex, reduced replicative lifespan (RLS) and are linked to a novel Sir2-independent RLS control pathway. Although transcript sequestration in...
Yan Liu

Centenarian hippocampus displays high levels of astrocytic metallothioneins

3 days 13 hours ago
The hippocampus is a brain area linked to cognition. The mechanisms that maintain cognitive activity in humans are poorly understood. Centenarians display extreme longevity which is generally accompanied by better quality of life, lower cognitive impairment, and reduced incidence of pathologies including neurodegenerative diseases. We performed transcriptomic studies in hippocampus samples from individuals of different ages (centenarians [≥97 years], old, and young) and identified a differential...
Ander Saenz-Antoñanzas

Accumulation of senescent cells in the adrenal gland induces hypersecretion of corticosterone via IL1beta secretion

3 days 13 hours ago
Aging progresses through the interaction of metabolic processes, including changes in the immune and endocrine systems. Glucocorticoids (GCs), which are regulated by the hypothalamic-pituitary-adrenal (HPA) axis, play an important role in regulating metabolism and immune responses. However, the age-related changes in the secretion mechanisms of GCs remain elusive. Here, we found that corticosterone (CORT) secretion follows a circadian rhythm in young mice, whereas it oversecreted throughout the...
Noriyuki Okudaira

Hypertension in an ageing population: Diagnosis, mechanisms, collateral health risks, treatments, and clinical challenges

4 days 13 hours ago
Ageing population is considerably increasing worldwide, which is considered to reflect an improved quality of life. However, longevity in the human lifespan has increased the burden of late-life illnesses including cancer, neurodegeneration, and cardiovascular dysfunction. Of these, hypertension is the most common condition with huge health risks, with an increased prevalence among the elderly. In this review, we outline the current guidelines for defining hypertension and examine the detailed...
Jin Hee Kim
3 hours 49 minutes ago
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