Aging & Longevity

MENDER: fast and scalable tissue structure identification in spatial omics data

1 month 3 weeks ago
Tissue structure identification is a crucial task in spatial omics data analysis, for which increasingly complex models, such as Graph Neural Networks and Bayesian networks, are employed. However, whether increased model complexity can effectively lead to improved performance is a notable question in the field. Inspired by the consistent observation of cellular neighborhood structures across various spatial technologies, we propose Multi-range cEll coNtext DEciphereR (MENDER), for tissue...
Zhiyuan Yuan

Human trials exploring anti-aging medicines

1 month 3 weeks ago
Here, we summarize the current knowledge on eight promising drugs and natural compounds that have been tested in the clinic: metformin, NAD^(+) precursors, glucagon-like peptide-1 receptor agonists, TORC1 inhibitors, spermidine, senolytics, probiotics, and anti-inflammatories. Multiple clinical trials have commenced to evaluate the efficacy of such agents against age-associated diseases including diabetes, cardiovascular disease, cancer, and neurodegenerative diseases. There are reasonable...
Leonard Guarente

Association of exercise with pan-cancer incidence and overall survival

1 month 3 weeks ago
Lavery et al. show that the association between exercise and risk of cancer varied as a function of organ site and amount of exercise. Exercise was also associated with a longevity benefit regardless of a cancer diagnosis or not. This study further highlights the importance of exercise as an effective cancer preventive strategy.
Jessica A Lavery

Hormesis determines lifespan

1 month 3 weeks ago
This paper addresses how long lifespan can be extended via multiple interventions, such as dietary supplements [e.g., curcumin, resveratrol, sulforaphane, complex phytochemical mixtures (e.g., Moringa, Rhodiola)], pharmaceutical agents (e.g., metformin), caloric restriction, intermittent fasting, exercise and other activities. This evaluation was framed within the context of hormesis, a biphasic dose response with specific quantitative features describing the limits of biological/phenotypic...
Edward J Calabrese

Microphysiological systems for human aging research

1 month 3 weeks ago
Recent advances in microphysiological systems (MPS), also known as organs-on-a-chip (OoC), enable the recapitulation of more complex organ and tissue functions on a smaller scale in vitro. MPS therefore provide the potential to better understand human diseases and physiology. To date, numerous MPS platforms have been developed for various tissues and organs, including the heart, liver, kidney, blood vessels, muscle, and adipose tissue. However, only a few studies have explored using MPS...
Seungman Park

Fission-independent compartmentalization of mitochondria during budding yeast cell division

1 month 3 weeks ago
Lateral diffusion barriers compartmentalize membranes to generate polarity or asymmetrically partition membrane-associated macromolecules. Budding yeasts assemble such barriers in the endoplasmic reticulum (ER) and the outer nuclear envelope at the bud neck to retain aging factors in the mother cell and generate naïve and rejuvenated daughter cells. However, little is known about whether other organelles are similarly compartmentalized. Here, we show that the membranes of mitochondria are...
Saori R Yoshii

Screens in aging-relevant human ALS-motor neurons identify MAP4Ks as therapeutic targets for the disease

1 month 3 weeks ago
Effective therapeutics is much needed for amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease mainly affecting motor neurons. By screening chemical compounds in human patient-derived and aging-relevant motor neurons, we identify a neuroprotective compound and show that MAP4Ks may serve as therapeutic targets for treating ALS. The lead compound broadly improves survival and function of motor neurons directly converted from human ALS patients. Mechanistically, it works as...
Meng-Lu Liu

Longevity interventions modulate mechanotransduction and extracellular matrix homeostasis in C. elegans

1 month 3 weeks ago
Dysfunctional extracellular matrices (ECM) contribute to aging and disease. Repairing dysfunctional ECM could potentially prevent age-related pathologies. Interventions promoting longevity also impact ECM gene expression. However, the role of ECM composition changes in healthy aging remains unclear. Here we perform proteomics and in-vivo monitoring to systematically investigate ECM composition (matreotype) during aging in C. elegans revealing three distinct collagen dynamics. Longevity...
Alina C Teuscher

FOXO1-mediated lipid metabolism maintains mammalian embryos in dormancy

1 month 3 weeks ago
Mammalian developmental timing is adjustable in vivo by preserving pre-implantation embryos in a dormant state called diapause. Inhibition of the growth regulator mTOR (mTORi) pauses mouse development in vitro, yet how embryonic dormancy is maintained is not known. Here we show that mouse embryos in diapause are sustained by using lipids as primary energy source. In vitro, supplementation of embryos with the metabolite L-carnitine balances lipid consumption, puts the embryos in deeper dormancy...
Vera A van der Weijden

YTHDC1 delays cellular senescence and pulmonary fibrosis by activating ATR in an m6A-independent manner

1 month 3 weeks ago
Accumulation of DNA damage in the lung induces cellular senescence and promotes age-related diseases such as idiopathic pulmonary fibrosis (IPF). Hence, understanding the mechanistic regulation of DNA damage repair is important for anti-aging therapies and disease control. Here, we identified an m6A-independent role of the RNA-binding protein YTHDC1 in counteracting stress-induced pulmonary senescence and fibrosis. YTHDC1 is primarily expressed in pulmonary alveolar epithelial type 2 (AECII)...
Canfeng Zhang

Transcriptional and epigenetic dysregulation impairs generation of proliferative neural stem and progenitor cells during brain aging

1 month 3 weeks ago
The decline in stem cell function during aging may affect the regenerative capacity of mammalian organisms; however, the gene regulatory mechanism underlying this decline remains unclear. Here we show that the aging of neural stem and progenitor cells (NSPCs) in the male mouse brain is characterized by a decrease in the generation efficacy of proliferative NSPCs rather than the changes in lineage specificity of NSPCs. We reveal that the downregulation of age-dependent genes in NSPCs drives cell...
Meiyang Li

Autophagy protein ATG-16.2 and its WD40 domain mediate the beneficial effects of inhibiting early-acting autophagy genes in C. elegans neurons

1 month 3 weeks ago
While autophagy genes are required for lifespan of long-lived animals, their tissue-specific roles in aging remain unclear. Here, we inhibited autophagy genes in Caenorhabditis elegans neurons, and found that knockdown of early-acting autophagy genes, except atg-16.2, increased lifespan, and decreased neuronal PolyQ aggregates, independently of autophagosomal degradation. Neurons can secrete protein aggregates via vesicles called exophers. Inhibiting neuronal early-acting autophagy genes, except...
Yongzhi Yang

Auto-suppression of Tet dioxygenases protects the mouse oocyte genome from oxidative demethylation

1 month 3 weeks ago
DNA cytosine methylation plays a vital role in repressing retrotransposons, and such derepression is linked with developmental failure, tumorigenesis and aging. DNA methylation patterns are formed by precisely regulated actions of DNA methylation writers (DNA methyltransferases) and erasers (TET, ten-eleven translocation dioxygenases). However, the mechanisms underlying target-specific oxidation of 5mC by TET dioxygenases remain largely unexplored. Here we show that a large low-complexity domain...
Xiao-Jie Zhang

Reduction of DHHC5-mediated beclin 1 S-palmitoylation underlies autophagy decline in aging

1 month 3 weeks ago
Autophagy is a lysosome-dependent degradation pathway essential for cellular homeostasis, which decreases with age. However, it is unclear how aging induces autophagy decline. Here we show the role of protein S-palmitoylation in autophagy. We identify the palmitoyl acyltransferase DHHC5 as a regulator of autophagy by mediating the palmitoylation of beclin 1, which in turn promotes the formation of ATG14L-containing class III phosphatidylinositol-3-kinase complex I and its lipid kinase activity...
Rui Guo

Longevity, demographic characteristics, and socio-economic status are linked to triiodothyronine levels in the general population

1 month 3 weeks ago
The hypothalamic-pituitary-thyroid (HPT) axis is fundamental to human biology, exerting central control over energy expenditure and body temperature. However, the consequences of normal physiologic HPT-axis variation in populations without diagnosed thyroid disease are poorly understood. Using nationally representative data from the 2007 to 2012 National Health and Nutrition Examination Survey, we explore relationships with demographic characteristics, longevity, and socio-economic factors. We...
Ralph I Lawton

Mitochondrial-derived vesicles in metabolism, disease, and aging

1 month 3 weeks ago
Mitochondria are central hubs of cellular metabolism and are tightly connected to signaling pathways. The dynamic plasticity of mitochondria to fuse, divide, and contact other organelles to flux metabolites is central to their function. To ensure bona fide functionality and signaling interconnectivity, diverse molecular mechanisms evolved. An ancient and long-overlooked mechanism is the generation of mitochondrial-derived vesicles (MDVs) that shuttle selected mitochondrial cargoes to target...
Tim König

What we talk about when we talk about spinal cord aging

1 month 3 weeks ago
Spinal cord-associated disorders are common in the elderly population; however, the mechanisms underlying spinal aging remain elusive. In a recent Nature paper, Sun et al. systemically analyzed aged spines in nonhuman primates and identified a new cluster of CHIT1-positive microglia that drives motor neuron senescence and subsequent spine aging.
Xianhong Ji

Elevated CSF GAP-43 is associated with accelerated tau accumulation and spread in Alzheimer's disease

1 month 3 weeks ago
In Alzheimer's disease, amyloid-beta (Aβ) triggers the trans-synaptic spread of tau pathology, and aberrant synaptic activity has been shown to promote tau spreading. Aβ induces aberrant synaptic activity, manifesting in increases in the presynaptic growth-associated protein 43 (GAP-43), which is closely involved in synaptic activity and plasticity. We therefore tested whether Aβ-related GAP-43 increases, as a marker of synaptic changes, drive tau spreading in 93 patients across the aging and...
Nicolai Franzmeier
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