Aging & Longevity

Restricting bioenergetic efficiency enhances longevity and mitochondrial redox capacity in Drosophila melanogaster

2 months ago
Mitochondria are essential for survival and as such, impairments in organelle homeostasis significantly accelerate age-related morbidity and mortality. Here, we determined the contribution of bioenergetic efficiency to life span and health span in Drosophila melanogaster utilizing the mitochondrial uncoupler BAM15. Life span was determined in flies fed a normal diet (ND) or high fat diet (HFD) supplemented with vehicle or BAM15. Locomotor function was determined by negative geotaxis assay in...
Analisa L Taylor

Clonally heritable gene expression imparts a layer of diversity within cell types

2 months ago
Cell types can be classified according to shared patterns of transcription. Non-genetic variability among individual cells of the same type has been ascribed to stochastic transcriptional bursting and transient cell states. Using high-coverage single-cell RNA profiling, we asked whether long-term, heritable differences in gene expression can impart diversity within cells of the same type. Studying clonal human lymphocytes and mouse brain cells, we uncovered a vast diversity of heritable gene...
Jeff E Mold

Nutrient-dependent regulation of a stable intron modulates germline mitochondrial quality control

2 months ago
Mitochondria are inherited exclusively from the mothers and are required for the proper development of embryos. Hence, germline mitochondrial quality is highly regulated during oogenesis to ensure oocyte viability. How nutrient availability influences germline mitochondrial quality control is unclear. Here we find that fasting leads to the accumulation of mitochondrial clumps and oogenesis arrest in Drosophila. Fasting induces the downregulation of the DIP1-Clueless pathway, leading to an...
Annabel Qi En Ng

Aging clock based on nucleosome reorganisation derived from cell-free DNA

2 months ago
Aging induces systematic changes in the distribution of nucleosomes, which affect gene expression programs. Here we reconstructed nucleosome maps based on cell-free DNA (cfDNA) extracted from blood plasma using four cohorts of people of different ages. We show that nucleosomes tend to be separated by larger genomic distances in older people, and age correlates with the nucleosome repeat length (NRL). Furthermore, we developed the first aging clock based on cfDNA nucleosomics. Machine learning...
Mariya Shtumpf

Children born after assisted reproduction more commonly carry a mitochondrial genotype associating with low birthweight

2 months ago
Children conceived through assisted reproductive technologies (ART) have an elevated risk of lower birthweight, yet the underlying cause remains unclear. Our study explores mitochondrial DNA (mtDNA) variants as contributors to birthweight differences by impacting mitochondrial function during prenatal development. We deep-sequenced the mtDNA of 451 ART and spontaneously conceived (SC) individuals, 157 mother-child pairs and 113 individual oocytes from either natural menstrual cycles or after...
Joke Mertens

New insights into the ontogeny, diversity, maturation and survival of long-lived plasma cells

2 months ago
Plasma cells are unique immune effectors, capable of producing large amounts of high-affinity antibodies that protect against pathogenic infections. Although most plasma cells have short lifespans, certain conditions or vaccinations can give rise to long-lived plasma cells (LLPCs) that provide individuals with lifelong protection against pathogen exposure. The nature of these LLPCs is poorly understood; however, recent studies have shed new light on the ontogeny, diversity, maturation and...
David R Fooksman

Signatures of cysteine oxidation on muscle structural and contractile proteins are associated with physical performance and muscle function in older adults: Study of Muscle, Mobility and Aging (SOMMA)

2 months ago
Oxidative stress is considered a contributor to declining muscle function and mobility during aging; however, the underlying molecular mechanisms remain poorly described. We hypothesized that greater levels of cysteine (Cys) oxidation on muscle proteins are associated with decreased measures of mobility. Herein, we applied a novel redox proteomics approach to measure reversible protein Cys oxidation in vastus lateralis muscle biopsies collected from 56 subjects in the Study of Muscle, Mobility...
Nicholas J Day

Restoration of norepinephrine release, cognitive performance, and dendritic spines by amphetamine in aged rat brain

2 months ago
Age-related dysfunctions in specific neurotransmitter systems likely play an important role in cognitive decline even in its most subtle forms. Therefore, preservation or improvement of cognition via augmentation of neurotransmission is a potential therapeutic strategy to prevent further cognitive deficits. Here we identified a particular neuronal vulnerability in the aged Fischer 344 rat brain, an animal model of neurocognitive aging. Specifically, we demonstrated a marked impairment in...
Serena Scognamiglio

Zn<sup>2+</sup>-dependent functional switching of ERp18, an ER-resident thioredoxin-like protein

2 months ago
ERp18 is an endoplasmic reticulum (ER)-resident thioredoxin (Trx) family protein, similar to cytosolic Trx1. The Trx-like domain occupies a major portion of the whole ERp18 structure, which is postulated to be an ER paralog of cytosolic Trx1. Here, we elucidate that zinc ion (Zn^(2+)) binds ERp18 through its catalytic motif, triggering oligomerization of ERp18 from a monomer to a trimer. While the monomeric ERp18 has disulfide oxidoreductase activity, the trimeric ERp18 acquires scavenger...
Chika Tsutsumi

Enhancing osteoporosis treatment with engineered mesenchymal stem cell-derived extracellular vesicles: mechanisms and advances

2 months ago
As societal aging intensifies, the incidence of osteoporosis (OP) continually rises. OP is a skeletal disorder characterized by reduced bone mass, deteriorated bone tissue microstructure, and consequently increased bone fragility and fracture susceptibility, typically evaluated using bone mineral density (BMD) and T-score. Not only does OP diminish patients' quality of life, but it also imposes a substantial economic burden on society. Conventional pharmacological treatments yield limited...
Yiman Chen

Corpora cavernosa fibroblasts mediate penile erection

2 months ago
Penile erection is mediated by the corpora cavernosa, a trabecular-like vascular bed that enlarges upon vasodilation, but its regulation is not completely understood. Here, we show that perivascular fibroblasts in the corpora cavernosa support vasodilation by reducing norepinephrine availability. The effect on penile blood flow depends on the number of fibroblasts, which is regulated by erectile activity. Erection dynamically alters the positional arrangement of fibroblasts, temporarily...
Eduardo Linck Guimaraes

Age-associated CD4<sup>+</sup> T cells with B cell-promoting functions are regulated by ZEB2 in autoimmunity

2 months ago
Aging is a significant risk factor for autoimmunity, and many autoimmune diseases tend to onset during adulthood. We conducted an extensive analysis of CD4^(+) T cell subsets from 354 autoimmune disease patients and healthy controls via flow cytometry and bulk RNA sequencing. As a result, we identified a distinct CXCR3^(mid)CD4^(+) effector memory T cell subset that expands with age, which we designated "age-associated helper T (ThA) cells". ThA cells exhibited both a cytotoxic phenotype and B...
Manaka Goto

Preventing metabolic disease: Part I

2 months 1 week ago
While the successes of modern medicine have significantly extended the human lifespan, the burden of chronic metabolic disease increasingly impacts the quality of life of almost two billion people worldwide. It is now imperative that we recognize metabolic disease as a pandemic and urgently prioritize preventive measures to halt its expansion.
Cell Metabolism editorial team

The cycling and aging mouse female reproductive tract at single-cell resolution

2 months 1 week ago
The female reproductive tract (FRT) undergoes extensive remodeling during reproductive cycling. This recurrent remodeling and how it shapes organ-specific aging remains poorly explored. Using single-cell and spatial transcriptomics, we systematically characterized morphological and gene expression changes occurring in ovary, oviduct, uterus, cervix, and vagina at each phase of the mouse estrous cycle, during decidualization, and into aging. These analyses reveal that fibroblasts play central-and...
Ivana Winkler

Unveiling the role of astrocytes in postoperative cognitive dysfunction

2 months 1 week ago
Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized by progressive cognitive decline and the accumulation of amyloid-beta plaques, tau tangles, and neuroinflammation in the brain. Postoperative cognitive dysfunction (POCD) is a prevalent and debilitating condition characterized by cognitive decline following neuroinflammation and oxidative stress induced by procedures. POCD and AD are two conditions that share similarities in the underlying mechanisms and...
Liang He

Heterotopic mineralization (ossification or calcification) in aged musculoskeletal soft tissues: A new candidate marker for aging

2 months 1 week ago
Aging can lead to various disorders in organisms and with the escalating impact of population aging, the incidence of age-related diseases is steadily increasing. As a major risk factor for chronic illnesses in humans, the prevention and postponement of aging have become focal points of research among numerous scientists. Aging biomarkers, which mirror molecular alterations at diverse levels in organs, tissues, and cells, can be used to monitor and evaluate biological changes associated with...
Guang-Chun Dai

Mitochondrial function in peripheral blood cells across the human lifespan

2 months 1 week ago
Mitochondrial dysfunction is considered a hallmark of aging. Up to now, a gradual decline of mitochondrial respiration with advancing age has mainly been demonstrated in human muscle tissue. A handful of studies have examined age-related mitochondrial dysfunction in human blood cells, and only with small sample sizes and mainly in platelets. In this study, we analyzed mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) and platelets from 308 individuals across the human...
Johannes K Ehinger

Recovery of isolated lithium through discharged state calendar ageing

2 months 1 week ago
Rechargeable Li-metal batteries have the potential to more than double the specific energy of the state-of-the-art rechargeable Li-ion batteries, making Li-metal batteries a prime candidate for next-generation high-energy battery technology^(1-3). However, current Li-metal batteries suffer from fast cycle degradation compared with their Li-ion battery counterparts^(2,3), preventing their practical adoption. A main contributor to capacity degradation is the disconnection of Li from the...
Wenbo Zhang
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