Aging & Longevity
Vorinostat, a potential hormetin, extends lifespan and enhances stress resistance via the SKN-1 pathway in Caenorhabditis elegans
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...
Clonal hematopoiesis-associated motoric deficits caused by monocyte-derived microglia accumulating in aging mice
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...
Dietary Restriction Mitigates Vascular Aging, Modulates the cGAS-STING Pathway and Reverses Macrophage-Like VSMC Phenotypes in Progeroid DNA-Repair-Deficient Ercc1(delta) (/-) Mice
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/-)...
Single-cell morphology encodes functional subtypes of senescence in aging human dermal fibroblasts
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...
Identification of Senomorphic miRNAs in Embryonic Progenitor and Adult Stem Cell-Derived Extracellular Vesicles
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...
Age-Dependent Regulation of Hippocampal Inflammation by the Mitochondrial Translocator Protein in Mice
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...
Self-report and actigraphy measures of sleep and domain-specific cognitive performance in older adults
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...
Photoactuating artificial muscle from supramolecular assembly of an overcrowded alkene-derived molecular switch
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...
Healthy diets for healthy aging
No abstract
Age-related changes in factors associated with self-rated health in Swedish older adults- findings from the Gothenburg H70 study cohort born 1930
CONCLUSION: The proportion of poor SRH decreases with age despite a higher frequency of somatic health conditions. Associated factors varied across ages, indicating that physical factors more strongly influence SRH in younger-old adults, while psychosocial factors have a greater impact on SRH in older-old adults.
Corrigendum: Boosting antioxidant self-defenses by grafting astrocytes rejuvenates the aged microenvironment and mitigates nigrostriatal toxicity in parkinsonian brain via an Nrf2-driven Wnt/β-catenin prosurvival axis
[This corrects the article DOI: 10.3389/fnagi.2020.00024.].
Identification of functional near-infrared spectroscopy for older adults with mild cognitive impairment: a systematic review
CONCLUSION: Research on fNIRS in elderly patients with MCI aims to provide an objective marker for MCI diagnosis. The current findings are mixed. However, these differences can be partly explained with the theoretical support from the interaction of cognitive load theory and scaffolding theory of aging and cognition, taking into account factors such as unspecified MCI subtypes, task difficulty, task design, monitoring duration, and population characteristics. Therefore, future studies should...
Longitudinal changes in blood-borne geroscience biomarkers: results from a population-based study
Multi-marker approaches are well suited for untangling the intrinsic complexity of aging and related conditions. Herein, we quantified (1) baseline concentrations of a panel of geroscience biomarkers pertaining to four biological domains (i.e., metabolism, inflammation, vascular/organ dysfunction and cellular senescence, and neurodegeneration) in individuals aged ≥60 years; (2) investigated linear and non-linear changes in biomarker levels over a 6-year period according to age and sex; and (3)...
Microbial metabolite drives ageing-related clonal haematopoiesis via ALPK1
Clonal haematopoiesis of indeterminate potential (CHIP) involves the gradual expansion of mutant pre-leukaemic haematopoietic cells, which increases with age and confers a risk for multiple diseases, including leukaemia and immune-related conditions¹. Although the absolute risk of leukaemic transformation in individuals with CHIP is very low, the strongest predictor of progression is the accumulation of mutant haematopoietic cells². Despite the known associations between CHIP and increased...
Relationships of social isolation and loneliness with healthy aging among older adults
CONCLUSIONS: A coexistence of social isolation and loneliness was associated with a substantially lower likelihood of healthy aging among women. Our findings highlight the importance of social support in extending women's healthspan beyond the management of traditional risk factors.
Intrinsic capacity trajectories and cardiovascular disease incidence among Chinese older adults: a population-based prospective cohort study
CONCLUSION: IC trajectory among Chinese older adults is heterogeneous. Low IC with slow declining is associated with an increased risk of CVD incidence.
LinAge2: providing actionable insights and benchmarking with epigenetic clocks
Biological aging is marked by a decline in resilience at the cellular and systemic levels, driving an exponential increase in mortality risk. Here, we evaluate several clinical and epigenetic clocks for their ability to predict mortality, demonstrating that clocks trained on survival and functional aging outperform those trained on chronological age. We present an enhanced clinical clock that predicts mortality more accurately and provides actionable insights for guiding personalized...
Genetics- and age-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated behaviors in SM/J mice
There are no appropriate mouse models to study the pathophysiology of spontaneous disc herniations in a wild-type setting. SM/J mice, a poor healer inbred strain, presented a high incidence of age-associated lumbar disc herniations with neurovascular innervations. Transcriptomic comparisons of the SM/J annulus fibrosus with human tissues showed shared pathways related to immune cell activation and inflammation. Notably, aged SM/J mice showed increased pain sensitization and neuroinflammation...
Tumor-Infiltrating Clonal Hematopoiesis
CONCLUSIONS: TI-CH increased the risk of disease recurrence or death among patients with NSCLC and the risk of death from any cause among patients with solid tumors. TI-CH remodeled the tumor immune microenvironment and accelerated tumor organoid growth, findings that support a role for an aging-related hematologic clonal proliferation in cancer evolution. (Funded by the Royal Society and others.).
TMBIM-2 links neuronal mitochondrial stress to systemic adaptation via calcium signaling
Mitochondrial function is critical for neuronal activity and systemic metabolic adaptation. In this issue, Li et al. (https://doi.org/10.1083/jcb.202408050) identify TMBIM-2 as a key regulator of calcium dynamics, coordinating the neuronal-to-intestinal mitochondrial unfolded protein response (UPRmt), pathogen-induced aversive learning, and aging.
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