Aging & Longevity

A phenotypic screening platform for identifying chemical modulators of astrocyte reactivity

1 month 3 weeks ago
Disease, injury and aging induce pathological reactive astrocyte states that contribute to neurodegeneration. Modulating reactive astrocytes therefore represent an attractive therapeutic strategy. Here we describe the development of an astrocyte phenotypic screening platform for identifying chemical modulators of astrocyte reactivity. Leveraging this platform for chemical screening, we identify histone deacetylase 3 (HDAC3) inhibitors as effective suppressors of pathological astrocyte...
Benjamin L L Clayton

Age-related changes in human skeletal muscle transcriptome and proteome are more affected by chronic inflammation and physical inactivity than primary aging

1 month 3 weeks ago
Evaluation of the influence of primary and secondary aging on the manifestation of molecular and cellular hallmarks of aging is a challenging and currently unresolved issue. Our study represents the first demonstration of the distinct role of primary aging and chronic inflammation/physical inactivity - the most important drivers of secondary aging, in the regulation of transcriptomic and proteomic profiles in human skeletal muscle. To achieve this purpose, young healthy people (n = 15), young (n...
Nadia S Kurochkina

Advanced age and female sex protect cerebral arteries from mitochondrial depolarization and apoptosis during acute oxidative stress

1 month 3 weeks ago
Aging increases reactive oxygen species (ROS) which can impair vascular function and contribute to brain injury. However, aging can also promote resilience to acute oxidative stress. Therefore, we tested the hypothesis that advanced age protects smooth muscle cells (SMCs) and endothelial cells (ECs) of posterior cerebral arteries (PCAs; diameter, ∼80 μm) during exposure to H(2) O(2) . PCAs from young (4-6 months) and old (20-26 months) male and female C57BL/6 mice were isolated and pressurized...
Charles E Norton

IgG is an aging factor that drives adipose tissue fibrosis and metabolic decline

1 month 3 weeks ago
Aging is underpinned by pronounced metabolic decline; however, the drivers remain obscure. Here, we report that IgG accumulates during aging, particularly in white adipose tissue (WAT), to impair adipose tissue function and metabolic health. Caloric restriction (CR) decreases IgG accumulation in WAT, whereas replenishing IgG counteracts CR's metabolic benefits. IgG activates macrophages via Ras signaling and consequently induces fibrosis in WAT through the TGF-β/SMAD pathway. Consistently, B...
Lexiang Yu

Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk

1 month 3 weeks ago
In mice, periodic cycles of a fasting mimicking diet (FMD) protect normal cells while killing damaged cells including cancer and autoimmune cells, reduce inflammation, promote multi-system regeneration, and extend longevity. Here, we performed secondary and exploratory analysis of blood samples from a randomized clinical trial (NCT02158897) and show that 3 FMD cycles in adult study participants are associated with reduced insulin resistance and other pre-diabetes markers, lower hepatic fat (as...
Sebastian Brandhorst

Deep learning models reveal replicable, generalizable, and behaviorally relevant sex differences in human functional brain organization

1 month 3 weeks ago
Sex plays a crucial role in human brain development, aging, and the manifestation of psychiatric and neurological disorders. However, our understanding of sex differences in human functional brain organization and their behavioral consequences has been hindered by inconsistent findings and a lack of replication. Here, we address these challenges using a spatiotemporal deep neural network (stDNN) model to uncover latent functional brain dynamics that distinguish male and female brains. Our stDNN...
Srikanth Ryali

HuR-positive stress granules: Potential targets for age-related osteoporosis

1 month 3 weeks ago
Aging impairs osteoblast function and bone turnover, resulting in age-related bone degeneration. Stress granules (SGs) are membrane-less organelles that assemble in response to stress via the recruitment of RNA-binding proteins (RBPs), and have emerged as a novel mechanism in age-related diseases. Here, we identified HuR as a bone-related RBP that aggregated into SGs and facilitated osteogenesis during aging. HuR-positive SG formation increased during osteoblast differentiation, and HuR...
Ying Huai

Genetic influences on circulating retinol and its relationship to human health

1 month 3 weeks ago
Retinol is a fat-soluble vitamin that plays an essential role in many biological processes throughout the human lifespan. Here, we perform the largest genome-wide association study (GWAS) of retinol to date in up to 22,274 participants. We identify eight common variant loci associated with retinol, as well as a rare-variant signal. An integrative gene prioritisation pipeline supports novel retinol-associated genes outside of the main retinol transport complex (RBP4:TTR) related to lipid biology,...
William R Reay

Leisure engagement in older age is related to objective and subjective experiences of aging

1 month 3 weeks ago
Leisure engagement has potential to slow health and functional decline in older age. However, the benefits of different leisure domains for different aspects of aging remains unclear. In 8771 older adults from the Health and Retirement Study (a longitudinal panel study), we measured engagement in physical, creative, cognitive, and community activities. Outcome-wide analyses used 23 aging experiences across seven domains eight years later (daily functioning, physical fitness, long-term physical...
Jessica K Bone

Spatially resolved transcriptome of the aging mouse brain

1 month 3 weeks ago
Brain aging is associated with cognitive decline, memory loss and many neurodegenerative disorders. The mammalian brain has distinct structural regions that perform specific functions. However, our understanding in gene expression and cell types within the context of the spatial organization of the mammalian aging brain is limited. Here we generated spatial transcriptomic maps of young and old mouse brains. We identified 27 distinguished brain spatial domains, including layer-specific subregions...
Cheng Wu

Opening avenues for treatment of neurodegenerative disease using post-biotics: Breakthroughs and bottlenecks in clinical translation

1 month 3 weeks ago
Recent studies have indicated the significant involvement of the gut microbiome in both human physiology and pathology. Additionally, therapeutic interventions based on microbiome approaches have been employed to enhance overall health and address various diseases including aging and neurodegenerative disease (ND). Researchers have explored potential links between these areas, investigating the potential pathogenic or therapeutic effects of intestinal microbiota in diseases. This article...
Bushra Bashir

Heart failure with preserved ejection fraction: everything the clinician needs to know

1 month 3 weeks ago
Heart failure with preserved ejection fraction (HFpEF) is increasingly recognised and diagnosed in clinical practice, a trend driven by an ageing population and a rise in contributing comorbidities, such as obesity and diabetes. Representing at least half of all heart failure cases, HFpEF is recognised as a complex clinical syndrome. Its diagnosis and management are challenging due to its diverse pathophysiology, varied epidemiological patterns, and evolving diagnostic and treatment approaches....
Patricia Campbell

The Role and Mechanism of RNA-binding Proteins in Bone Metabolism and Osteoporosis

1 month 3 weeks ago
Osteoporosis is a prevalent chronic metabolic bone disease that poses a significant risk of fractures or mortality in elderly individuals. Its pathophysiological basis is often attributed to postmenopausal estrogen deficiency and natural aging, making the progression of primary osteoporosis among elderly people, especially older women, seemingly inevitable. The treatment and prevention of osteoporosis progression have been extensively discussed. Recently, as researchers delve deeper into the...
Jiaqiang Wu

Epigenetic regulations of cellular senescence in osteoporosis

1 month 3 weeks ago
Osteoporosis (OP) is a prevalent age-related disease that is characterized by a decrease in bone mineral density (BMD) and systemic bone microarchitectural disorders. With age, senescent cells accumulate and exhibit the senescence-associated secretory phenotype (SASP) in bone tissue, leading to the imbalance of bone homeostasis, osteopenia, changes in trabecular bone structure, and increased bone fragility. Cellular senescence in the bone microenvironment involves osteoblasts, osteoclasts, and...
Shaochuan Huo

CALPHAD accelerated design of advanced full-Zintl thermoelectric device

1 month 3 weeks ago
Since thermoelectric materials have different physical and chemical properties, the design of contact layers requires dedicated efforts, and the welding temperatures are distinctly different. Therefore, a general interface design and connection technology can greatly facilitate the development of thermoelectric devices. Herein, we proposed a screening strategy for the contact materials based on the calculation of phase diagram method, and Mg(2)Ni has been identified as a matched contact layer...
Li Yin

Phospholipids with two polyunsaturated fatty acyl tails promote ferroptosis

1 month 3 weeks ago
Phospholipids containing a single polyunsaturated fatty acyl tail (PL-PUFA(1)s) are considered the driving force behind ferroptosis, whereas phospholipids with diacyl-PUFA tails (PL-PUFA(2)s) have been rarely characterized. Dietary lipids modulate ferroptosis, but the mechanisms governing lipid metabolism and ferroptosis sensitivity are not well understood. Our research revealed a significant accumulation of diacyl-PUFA phosphatidylcholines (PC-PUFA(2)s) following fatty acid or phospholipid...
Baiyu Qiu

Non-invasive modulation of meningeal lymphatics ameliorates ageing and Alzheimer's disease-associated pathology and cognition in mice

1 month 3 weeks ago
Meningeal lymphatic vessels (mLVs) have been shown to be involved in amyloid beta (Aβ) clearance, which is considered as a potential therapeutic target for Alzheimer's disease (AD). In this study, based on the superficial spatial distribution of mLVs, a near-infrared light is employed to modulate lymphatic drainage, significantly improving cognition of both aged and AD (5xFAD and APP/PS1) mice, and alleviating AD-associated pathology by reducing Aβ deposition, neuroinflammation and neuronal...
Miao Wang

Rejuvenation as the origin of planar defects in the CrCoNi medium entropy alloy

1 month 3 weeks ago
High or medium- entropy alloys (HEAs/MEAs) are multi-principal element alloys with equal atomic elemental composition, some of which have shown record-breaking mechanical performance. However, the link between short-range order (SRO) and the exceptional mechanical properties of these alloys has remained elusive. The local destruction of SRO by dislocation glide has been predicted to lead to a rejuvenated state with increased entropy and free energy, creating softer zones within the matrix and...
Yang Yang

Pro-ferroptotic signaling promotes arterial aging via vascular smooth muscle cell senescence

1 month 3 weeks ago
Senescence of vascular smooth muscle cells (VSMCs) contributes to aging-related cardiovascular diseases by promoting arterial remodelling and stiffness. Ferroptosis is a novel type of regulated cell death associated with lipid oxidation. Here, we show that pro-ferroptosis signaling drives VSMCs senescence to accelerate vascular NAD^(+) loss, remodelling and aging. Pro-ferroptotic signaling is triggered in senescent VSMCs and arteries of aged mice. Furthermore, the activation of pro-ferroptotic...
Di-Yang Sun
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