Aging & Longevity

3D Mitochondrial Structure in Aging Human Skeletal Muscle: Insights Into MFN-2-Mediated Changes

6 months 1 week ago
Age-related skeletal muscle atrophy, known as sarcopenia, is characterized by loss of muscle mass, strength, endurance, and oxidative capacity. Although exercise has been shown to mitigate sarcopenia, the underlying governing mechanisms are poorly understood. Mitochondrial dysfunction is implicated in aging and sarcopenia; however, few studies explore how mitochondrial structure contributes to this dysfunction. In this study, we sought to understand how aging impacts mitochondrial...
Estevão Scudese

Deciphering Immunosenescence From Child to Frailty: Transcriptional Changes, Inflammation Dynamics, and Adaptive Immune Alterations

6 months 1 week ago
Aging induces significant alterations in the immune system, with immunosenescence contributing to age-related diseases. Peripheral blood mononuclear cells (PBMCs) offer a convenient and comprehensive snapshot of the body's immune status. In this study, we performed an integrated analysis of PBMCs using both bulk-cell and single-cell RNA-seq data, spanning from children to frail elderlies, to investigate age-related changes. We observed dynamic changes in the PBMC transcriptome during healthy...
Wenpu Lai

Altering metabolism programs cell identity via NAD<sup>+</sup>-dependent deacetylation

6 months 1 week ago
Cells change their metabolic profiles in response to underlying gene regulatory networks, but how can alterations in metabolism encode specific transcriptional instructions? Here, we show that forcing a metabolic change in embryonic stem cells (ESCs) promotes a developmental identity that better approximates the inner cell mass (ICM) of the early mammalian blastocyst in cultures. This shift in cellular identity depends on the inhibition of glycolysis and stimulation of oxidative phosphorylation...
Robert A Bone

Stromal lipid species dictate melanoma metastasis and tropism

6 months 1 week ago
Cancer cells adapt to signals in the tumor microenvironment (TME), but the TME cues that impact metastasis and tropism are still incompletely understood. We show that abundant stromal lipids from young subcutaneous adipocytes, including phosphatidylcholines, are taken up by melanoma cells, where they upregulate melanoma PI3K-AKT signaling, fatty acid oxidation, oxidative phosphorylation (OXPHOS) leading to oxidative stress, resulting in decreased metastatic burden. High OXPHOS melanoma cells...
Shilpa Gurung

Cognitive frailty: a useful concept or a source of confusion? Insights from a survey of European geriatricians

6 months 1 week ago
CONCLUSIONS: There is no clear consensus opinion among geriatricians in Europe on the definition of 'cognitive frailty'. While there is some core support for the IANA-IAGG definition, it is not intuitive to those not already familiar with the term. The variance in the current understanding of cognitive frailty among geriatricians suggests the time is right for a meaningful debate on this issue. While there is ongoing, growing research on a shared pathophysiology between physical frailty and...
Suzanne Timmons

Inactivity is isolation: insights from a sedentary time intervention in assisted living

6 months 1 week ago
CONCLUSIONS: The natural communal setting of assisted living, along with supportive staff, presents a valuable opportunity to promote active aging, which is a complex interplay of social and movement behaviour. Our preliminary findings suggest that in addition to supporting individual behaviour change, a comprehensive approach that addresses the environment, social engagement, and staff engagement is needed in this setting. Future interventions should consider addressing each of these components...
Irmina Klicnik

Proactive end-of-life conversations in residential care homes: a qualitative interview study exploring residents' and family members' experiences

6 months 1 week ago
CONCLUSIONS: Proactive end-of-life conversations generated several beneficial outcomes for residents and family members, including those with cognitive decline. The study demonstrated that the conversations may strengthen person-centered care and family support in this context. Based on these findings, proactive end-of-life conversations have the potential for use by residential care home staff.
Åsa Mikaelsson

Vorinostat, a potential hormetin, extends lifespan and enhances stress resistance via the SKN-1 pathway in Caenorhabditis elegans

6 months 1 week ago
Vorinostat, a pan histone deacetylases (HDACs) inhibitor clinically approved for cutaneous T-cell lymphoma, exerts therapeutic effects by inducing tumor cell death and cycle arrest. Intriguingly, a previously unrecognized hormetic role of low-dose vorinostat in Caenorhabditis elegans. Subtoxic concentrations of vorinostat (1 μM) significantly extended lifespan, enhanced healthspan, and improved resistance to oxidative and heat stress, while ameliorating Aβ-induced paralysis. qPCR analysis...
Shuai Huang

Clonal hematopoiesis-associated motoric deficits caused by monocyte-derived microglia accumulating in aging mice

6 months 1 week ago
Microglia are parenchymal brain macrophages that are established during embryogenesis and form a self-containing cellular compartment that resists seeding with cells derived from adult definitive hematopoiesis. We report that monocyte-derived macrophages (MoMΦs) accumulate in the brain of aging mice with distinct topologies, including the nigrostriatum and medulla but not the frontal cortex. Parenchymal MoMΦs adopt bona fide microglia morphology and expression profiles. Due to their...
Jung-Seok Kim

Dietary Restriction Mitigates Vascular Aging, Modulates the cGAS-STING Pathway and Reverses Macrophage-Like VSMC Phenotypes in Progeroid DNA-Repair-Deficient Ercc1(delta) (/-) Mice

6 months 1 week ago
Aging is a major risk factor for cardiovascular diseases, and the accumulation of DNA damage significantly contributes to the aging process. This study aimed to identify the underlying molecular mechanisms of vascular aging in DNA-repair-deficient progeroid Ercc1^(Δ/-) mice and to explore the therapeutic effect of dietary restriction (DR). RNA sequencing analysis revealed that DR reversed gene expression of vascular aging processes, including extracellular matrix remodeling, in the Ercc1^(Δ/-)...
S J M Stefens

Single-cell morphology encodes functional subtypes of senescence in aging human dermal fibroblasts

6 months 1 week ago
Cellular senescence, a hallmark of aging, reveals context-dependent phenotypes across multiple biological length scales. Despite its mechanistic importance, identifying and characterizing senescence across cell populations is challenging. Using primary dermal fibroblasts, we combined single-cell imaging, machine learning, several induced senescence conditions, and multiple protein biomarkers to define functional senescence subtypes. Single-cell morphology analysis revealed 11 distinct morphology...
Pratik Kamat

Identification of Senomorphic miRNAs in Embryonic Progenitor and Adult Stem Cell-Derived Extracellular Vesicles

6 months 1 week ago
Extracellular vesicles (EVs) are secreted by most cell types, transmitting crucial signaling molecules like proteins, small RNAs, and DNA. We previously demonstrated that EVs from murine and human mesenchymal stem cells (MSCs) functioned as senomorphics to suppress markers of senescence and the inflammatory senescence-associated secretory phenotype (SASP) in cell culture and in aged mice. Here we demonstrate that EVs from additional types of human adult stem cells and embryonic progenitor cells...
Tianpeng Zhang

Age-Dependent Regulation of Hippocampal Inflammation by the Mitochondrial Translocator Protein in Mice

6 months 1 week ago
The mitochondrial translocator protein (TSPO) is a biomarker of inflammation associated with neurodegenerative diseases, widely regarded to be upregulated in the aging brain. Here we investigated the interaction between aging and TSPO immunomodulatory function in the mouse hippocampus, a region severely affected in Alzheimer's Disease (AD). Surprisingly, we found that TSPO levels were decreased in brain innate immune populations in aging. Aging resulted in a reversal of TSPO knockout...
Kei Onn Lai

Self-report and actigraphy measures of sleep and domain-specific cognitive performance in older adults

6 months 2 weeks ago
Poor sleep is associated with worse cognitive function in older adults. However, nuanced associations between sleep and cognition might be masked by the multidimensional nature of sleep which requires multiple approaches (e.g., self-report and actigraphy) to gain meaningful insight. We investigated associations of sleep with cognition and hypothesized that the most consistent association would be between self-reported sleep duration and actigraphy-measured wake after sleep onset (WASO). We...
Kelsey R Sewell

Photoactuating artificial muscle from supramolecular assembly of an overcrowded alkene-derived molecular switch

6 months 2 weeks ago
The amplification of molecular motion along length scales for macroscopic muscle-like functions, based on supramolecular polymers, provides attractive opportunities ranging from soft actuators to responsive biomedical materials. Taking the challenge to reveal dynamic assembly parameters governing muscle functions, we present the design of a photoswitch amphiphile based on an overcrowded alkene-derived core, and developed supramolecular artificial muscles. Going from molecular motor amphiphile...
Adrien Combe
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