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Fueling the Fire: Metabolic Dysfunction and Senescence as Drivers of Lung Aging and Disease - PubMed
2 months ago
- Cellular senescence is a key driver of chronic lung diseases like pulmonary fibrosis, COPD, and asthma.
- Mitochondrial dysfunction and the '4 Ms' (morphology, mitophagy, metabolism, metabolites) play a significant role in senescence pathways.
- The review discusses healthy lung aging, senescence-related pathomechanisms in chronic lung diseases, and current therapeutic targets.
- Emerging concepts and knowledge gaps are highlighted to improve therapeutic strategies and future research.
Calcific Aortopathy in Response to Aging and Injury - PubMed
2 months ago
- Calcific aortopathy is a common condition in aging populations, particularly in westernized societies.
- Calcification often starts in the abdominal aorta before affecting the thoracic aorta and aortic valves.
- Conditions like metabolic syndrome, chronic kidney disease, and irradiation can accelerate calcification.
- Calcification is linked to increased cardiovascular mortality and neurocognitive decline.
- Recent research highlights the role of innate immunity, senescence, and osteogenic mechanisms in calcific aortopathy.
- There is potential for new medical treatments to prevent or treat calcific aortopathy in the coming decade.
p38 MAPK orchestrates cross-tissue potassium homeostasis for survival - PubMed
2 months ago
- p38 MAPK-ATF-7 pathway regulates cross-tissue potassium homeostasis in C. elegans.
- CATP-3 P-type ATPase pump in the hypodermis is upregulated during potassium deficiency.
- This mechanism involves both cell-autonomous and ASI neuronal signals.
- The pathway is distinct from osmotic stress responses and is conserved across species.
- Findings link potassium regulation to lifespan, stress signaling, and innate immunity.
- Potential implications for aging and age-related diseases are suggested.
Methylmalonic Acid, an Aging-Associated Metabolite, Accelerates Intervertebral Disc Degeneration by Inducing Disc Vascularization via the CCL7/JAK2-STAT3/VEGF Signaling Axis - PubMed
2 months ago
- Methylmalonic acid (MMA) levels are significantly elevated in intervertebral discs (IVDs) of elderly individuals, suggesting its role in aging-induced intervertebral disc degeneration (IVDD).
- MMA treatment in nucleus pulposus cells (NPCs) leads to upregulation of catabolic markers and downregulation of anabolic markers, accelerating IVDD progression.
- MMA upregulates CCL7 expression in NPCs, enhancing JAK2/STAT3 signaling and increasing vascular endothelial growth factor (VEGF) expression, promoting disc vascularization.
- Disc vascularization is identified as a key factor in IVDD progression, with VEGF as a potential therapeutic target.
- Lenvatinib, a VEGF receptor inhibitor, was shown to delay IVDD progression in rescue experiments.
The STAT3 Paradox in Aging: Molecular Mechanisms and Targeted Therapeutic Strategies - PubMed
2 months ago
- STAT3 plays dual roles in aging, both promoting and inhibiting senescence.
- Key posttranslational modifications (PTMs) like phosphorylation (Y705, S727), acetylation, and methylation regulate STAT3 activity and localization.
- Y705 phosphorylation of STAT3 mainly promotes aging by driving inflammation, fibrosis, and mitochondrial dysfunction.
- S727 phosphorylation of STAT3 has potential anti-aging effects by maintaining stem cell properties and tissue regeneration.
- Other PTMs such as sulphenylation and O-GlcNAcylation also influence STAT3-mediated aging processes.
- The paradoxical roles of STAT3 are due to cellular/tissue specificity, signaling crosstalk, and temporal activation dynamics.
- Potential anti-aging strategies targeting STAT3 include small-molecule inhibitors, natural compounds, epigenetic modulators, and gene-based therapies.
- Understanding context-dependent STAT3 signaling and precise targeting of PTMs is crucial for developing effective anti-aging therapies.
A Multi-Organ Atlas Links Gut Microbial Metabolites to Systemic Redox Changes in Aging Mice - PubMed
2 months ago
- A multi-organ, multi-omics atlas was created to study gut microbial metabolites and systemic redox changes in aging mice.
- Aging was found to deplete protective circulating metabolites like lysophosphatidylcholines (LPCs) and increase pro-oxidative microbial catabolites such as TMAO and IAA.
- This microbial-metabolic shift disrupted lipid transport and redox balance, leading to organ-specific vulnerabilities in the liver, lungs, and cortex.
- A meta-analysis of 40 studies confirmed that microbial remodeling is linked to aging phenotypes, including intestinal barrier integrity, inflammation, and oxidative stress.
- The findings suggest gut-derived metabolic reprogramming as a modifiable driver of systemic aging, offering potential therapeutic targets.
Daily multivitamin use may slow biological aging: COSMOS trial results
2 months ago
- Daily multivitamin intake over two years slowed biological aging in older adults by about four months.
- Participants with accelerated biological aging at the start of the trial showed greater benefits.
- The study used epigenetic clocks to measure changes in DNA methylation, tracking biological aging.
- Results were derived from the COSMOS trial, involving 958 healthy participants averaging 70 years old.
- The multivitamin group showed significant slowing in two epigenetic clocks predictive of mortality.
- Future research will explore if benefits persist post-trial and extend to clinical outcomes like cognition and cancer reduction.
- The study highlights accessible interventions for healthier aging, supported by NIH and industry partnerships.
Collagen gene expression is linked to aging and lifespan extension in C. elegans - PubMed
2 months ago
- Collagen gene expression declines with age in C. elegans, with 16 collagen genes consistently downregulated, marking it as a genetic hallmark of aging.
- Collagen upregulation is observed in 84% of long-lived conditions, identifying it as a conserved signature of lifespan extension.
- K-means clustering using π-values revealed functional, tissue-associated subsets of collagens, with distinct clusters associated with aging, lifespan extension, and structural integrity.
- Aging-associated collagens are enriched in hypodermal collagens (Cluster 1), while lifespan-extension collagens overlap with intestine-enriched subsets (Cluster 2).
- Cluster 3 likely represents structural collagens contributing to cuticle and muscle integrity.
- Collagens are dynamic regulators of aging and longevity, suggesting potential as biomarkers and targets for promoting healthy aging across species.
The Dual Role of Extracellular Vesicles in Aging and Age-Related Diseases: Pathophysiology and Therapeutic Potential - PubMed
2 months ago
- Aging is a complex process leading to loss of physiological integrity and increased risk of chronic diseases.
- Extracellular vesicles (EVs) play a dual role in aging and age-related diseases, both contributing to pathology and offering therapeutic potential.
- EVs from senescent or diseased cells propagate inflammation, oxidative stress, and other harmful processes.
- EVs from stem cells or healthy tissues can restore balance, enhance function, and promote tissue repair.
- EVs hold promise as diagnostic biomarkers and treatments for aging-related conditions, despite challenges like rapid clearance.
Simultaneous spatial transcriptomics and morphology profiling as tools to explore how microglia change with age - PubMed
2 months ago
- Combined multiplexed error-robust fluorescence in situ hybridization with immunohistochemistry to study microglia in young and aged mouse brains.
- Revealed that mRNA spatial organization varies across microglial states, showing distinct localization patterns within their processes.
- Identified a subpopulation of disease-associated-like microglia with ramified morphology, challenging conventional assumptions about morphology and microglial states.
- Found that aging reshapes mRNA distributions and co-localization networks, shifting microglial programs towards migration and catabolic regulation.
- Highlights the role of subcellular transcript organization in shaping microglial morphology and function, offering new research avenues in health, disease, and aging.
What changes happen in the aging brain?
2 months ago
- Salk Institute scientists created a comprehensive single-cell atlas of epigenetic changes in the aging mouse brain.
- The atlas includes data from eight brain regions and 36 distinct brain cell types, profiling over 200,000 single cells.
- Key findings include age-related methylation changes, particularly in non-neuronal cells, and increased activity of transposable elements.
- The study utilized spatial transcriptomics to map gene expression, revealing regional differences in aging.
- The dataset is publicly available on AWS and GEO, facilitating global research collaboration.
- Deep-learning models were developed to predict age-related gene expression changes, aiding future research.
- The study highlights the importance of cell type-specific and region-specific understanding of brain aging.
Lifelong behavioral screen reveals an architecture of vertebrate aging - PubMed
2 months ago
- A platform was developed for high-resolution continuous behavioral tracking of African killifish across their natural lifespan.
- Distinct individual aging trajectories were observed, with behaviors of long-lived animals differing from short-lived ones early in life.
- Behavioral differences were linked to organ-specific transcriptomic shifts.
- Machine-learning models accurately inferred age and predicted future lifespan based on behavior at a young age.
- Animals progressed through adulthood in a sequence of stable, stereotyped behavioral stages with abrupt transitions, revealing a structured architecture of aging.
Chronic inflammation as a driving factor for sarcopenia: an update on pathophysiology and future therapeutic targets - PubMed
2 months ago
- Sarcopenia is an age-related decline in muscle mass, strength, and function, impacting older adults' quality of life.
- Chronic inflammation contributes to sarcopenia via cellular senescence, oxidative stress, mitochondrial dysfunction, and gut microbiota dysbiosis.
- Obesity exacerbates sarcopenia, leading to sarcopenic obesity, which worsens muscle loss and functional impairment.
- Interventions like exercise, nutritional supplementation, and combined approaches improve muscle mass and reduce inflammation.
- Anti-inflammatory agents and treatments targeting inflammatory pathways show promise in managing sarcopenia.
- Key inflammatory cytokines (CRP, IL-6, TNF-α) regulate muscle protein metabolism and may serve as biomarkers.
- Understanding inflammation's role in sarcopenia aids in developing early diagnostics and targeted therapies.
Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming - PubMed
2 months ago
- Cellular senescence is a key mechanism in aging and age-related diseases.
- Early senolytics like navitoclax and D+Q showed promise but had drawbacks like thrombocytopenia and variable efficacy.
- Next-gen strategies include immune-based senolysis, tissue-precision PROTACs, and microbiome-epigenetic approaches.
- Immune-based senolysis targets immune evasion of senescent cells using methods like CAR T cells and metabolic vulnerabilities.
- Tissue-precision PROTACs degrade anti-apoptotic proteins locally to reduce systemic toxicity.
- Microbiome-epigenetic strategies use SCFAs and dietary interventions to enhance senolytic efficacy and modulate the SASP.
- Challenges remain, including immunopathology, manufacturing complexity, and long-term safety concerns.
Histone modification clocks for robust cross-species biological age prediction and elucidating senescence regulation - PubMed
2 months ago
- Histone modifications offer a new method for biological age prediction, overcoming DNA methylation-based clock limitations.
- Developed 36 tissue-specific histone modification clocks using ChIP-seq data from six tissues and six histone marks.
- Clocks showed resilience to noise, comparable to DNA methylation clocks, and detected age acceleration in leukemia.
- Identified nonlinear aging trajectories with peak modification levels at midlife, revealing new epigenetic aging dynamics.
- Observed age-related fragmentation of super enhancer regions, indicating progressive chromatin disorganization.
- Validated a causal role of an H3K27ac peak near IGF2BP3 in cellular senescence via TRA2A expression regulation.
- Demonstrated histone-based clocks' applicability in Drosophila, highlighting evolutionary conservation and broader utility.
- Established histone modifications as robust, biologically meaningful aging biomarkers across species.
Cerebral collateral arteriogenesis and cerebrovascular reserve in aged and diet-induced obese mice after unilateral common carotid occlusion - PubMed
2 months ago
- The study investigated the effects of aging and diet-induced obesity on cerebral collateral arteriogenesis and cerebrovascular reserve after right common carotid artery occlusion (RCCAO) in mice.
- Young mice showed significant arteriogenesis in the circle of Willis (COW) and pial collaterals post-RCCAO, leading to full recovery of baseline cerebral blood flow (CBF).
- Aging progressively reduced arteriogenesis, resulting in partial or no CBF recovery in aging and aged mice, respectively.
- Cerebrovascular reserve was found to diminish with advancing age.
- Diet-induced obesity had milder effects on arteriogenesis compared to aging.
- The study highlights that cerebral collateral arteriogenesis is crucial for cerebrovascular reserve post-arterial occlusion and declines with age.
Grandparents are glued to their phones, families are worried [video]
2 months ago
- Charlie Warzel's essay in The Atlantic discusses older adults' increased screen time.
- Younger generations express concern over grandparents' phone usage, questioning if it's harmful or a projection of their own screen time anxieties.
- The conversation explores family dynamics, technology's role, and loneliness in older adults.
Mechanistic Modulation of Autophagy by Bioactive Natural Products: Implications for Human Aging and Longevity - PubMed
2 months ago
- Autophagy is a crucial intracellular process for maintaining cellular homeostasis, which becomes dysregulated with aging.
- Bioactive natural products from plants, foods, and marine organisms can modulate autophagy, offering potential anti-aging benefits.
- These compounds regulate autophagy via key pathways like AMPK, PI3K/AKT/mTOR, SIRT1, and FOXO, and mitigate oxidative stress and inflammation.
- Natural compounds such as polyphenols, flavonoids, alkaloids, terpenoids, and carotenoids can restore autophagic flux and prevent excessive autophagy-induced cell death.
- The review discusses both experimental and clinical evidence supporting the geroprotective effects of autophagy-modulating natural products.
- Challenges include bioavailability and dose-dependent effects, but these compounds hold promise for aging intervention strategies.
The Role of Ketogenic Diet and β-Hydroxybutyrate in the Prevention of Muscle Catabolism and Sarcopenia in Aging Populations: Mechanisms, Evidence, and Clinical Perspectives - PubMed
2 months ago
- Sarcopenia is a progressive loss of skeletal muscle mass, strength, and function, posing a public health challenge in aging populations.
- Ketogenic diets (KDs) and β-hydroxybutyrate (βOHB) may support muscle health in aging through energy provision and signaling pathways.
- βOHB acts as both an energy substrate and a signaling molecule, influencing histone deacetylase and inflammatory pathways.
- Nutritional ketosis in humans typically results in βOHB levels of 0.5-3.0 mM, potentially engaging beneficial signaling pathways.
- Preclinical studies show that long-term ketogenic diets preserve muscle mass, strength, and mitochondrial function in aging models.
- Clinical evidence suggests protein-adequate ketogenic diets, combined with exercise, may help preserve fat-free mass and improve function.
- Exogenous ketones may enhance post-exercise anabolic signaling, offering additional benefits for muscle health.
- Ketogenic diets show promise as an adjunctive strategy for sarcopenia prevention, but long-term clinical trials are needed to confirm efficacy and safety.
Sleep health in the older adults: Architecture, circadian changes, and common sleep disorders - PubMed
2 months ago
- Population aging increases sleep-related complaints among older adults, impacting cognitive function, physical health, and quality of life.
- Age-related changes include reduced slow-wave and REM sleep, decreased sleep efficiency, increased fragmentation, and circadian amplitude dampening.
- Common sleep disorders in older adults include insomnia (20-40%), obstructive sleep apnea (>30%), restless legs syndrome, and REM sleep behavior disorder.
- Chronic sleep disturbances are linked to cognitive decline, cardiovascular disease, falls, frailty, and mortality.
- Cognitive-behavioral therapy is a first-line treatment for insomnia, while dual orexin receptor antagonists show promise.
- Continuous positive airway pressure is standard for obstructive sleep apnea, though adherence is challenging.
- Future research priorities include longitudinal studies in the oldest-old, circadian mechanism investigations, behavioral interventions, and equity-focused research.

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#aging

Fueling the Fire: Metabolic Dysfunction and Senescence as Drivers of Lung Aging and Disease - PubMed

Calcific Aortopathy in Response to Aging and Injury - PubMed

p38 MAPK orchestrates cross-tissue potassium homeostasis for survival - PubMed

Methylmalonic Acid, an Aging-Associated Metabolite, Accelerates Intervertebral Disc Degeneration by Inducing Disc Vascularization via the CCL7/JAK2-STAT3/VEGF Signaling Axis - PubMed

The STAT3 Paradox in Aging: Molecular Mechanisms and Targeted Therapeutic Strategies - PubMed

A Multi-Organ Atlas Links Gut Microbial Metabolites to Systemic Redox Changes in Aging Mice - PubMed

Daily multivitamin use may slow biological aging: COSMOS trial results

Collagen gene expression is linked to aging and lifespan extension in C. elegans - PubMed

The Dual Role of Extracellular Vesicles in Aging and Age-Related Diseases: Pathophysiology and Therapeutic Potential - PubMed

Simultaneous spatial transcriptomics and morphology profiling as tools to explore how microglia change with age - PubMed

What changes happen in the aging brain?

Lifelong behavioral screen reveals an architecture of vertebrate aging - PubMed

Chronic inflammation as a driving factor for sarcopenia: an update on pathophysiology and future therapeutic targets - PubMed

Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming - PubMed

Histone modification clocks for robust cross-species biological age prediction and elucidating senescence regulation - PubMed

Cerebral collateral arteriogenesis and cerebrovascular reserve in aged and diet-induced obese mice after unilateral common carotid occlusion - PubMed

Grandparents are glued to their phones, families are worried [video]

Mechanistic Modulation of Autophagy by Bioactive Natural Products: Implications for Human Aging and Longevity - PubMed

The Role of Ketogenic Diet and β-Hydroxybutyrate in the Prevention of Muscle Catabolism and Sarcopenia in Aging Populations: Mechanisms, Evidence, and Clinical Perspectives - PubMed

Sleep health in the older adults: Architecture, circadian changes, and common sleep disorders - PubMed