Aging & Longevity
Exosomal miR-302b rejuvenates aging mice by reversing the proliferative arrest of senescent cells
Cellular senescence, a hallmark of aging, involves a stable exit from the cell cycle. Senescent cells (SnCs) are closely associated with aging and aging-related disorders, making them potential targets for anti-aging interventions. In this study, we demonstrated that human embryonic stem cell-derived exosomes (hESC-Exos) reversed senescence by restoring the proliferative capacity of SnCs in vitro. In aging mice, hESC-Exos treatment remodeled the proliferative landscape of SnCs, leading to...
Exercise and exerkines: Mechanisms and roles in anti-aging and disease prevention
Aging is a complex biological process characterized by increased inflammation and susceptibility to various age-related diseases, including cognitive decline, osteoporosis, and type 2 diabetes. Exercise has been shown to modulate mitochondrial function, immune responses, and inflammatory pathways, thereby attenuating aging through the regulation of exerkines secreted by diverse tissues and organs. These bioactive molecules, which include hepatokines, myokines, adipokines, osteokines, and...
Age-Trajectories of Higher-Order Diffusion Properties of Major Brain Metabolites in Cerebral and Cerebellar Gray Matter Using In Vivo Diffusion-Weighted MR Spectroscopy at 3T
Healthy brain aging involves changes in both brain structure and function, including alterations in cellular composition and microstructure across brain regions. Unlike diffusion-weighted MRI (dMRI), diffusion-weighted MR spectroscopy (dMRS) can assess cell-type specific microstructural changes, providing indirect information on both cell composition and microstructure through the quantification and interpretation of metabolites' diffusion properties. This work investigates age-related changes...
V-ATPase Disassembly at the Yeast Lysosome-Like Vacuole Is a Phenotypic Driver of Lysosome Dysfunction in Replicative Aging
Declines in lysosomal acidification and function with aging are observed in organisms ranging from yeast to humans. V-ATPases play a central role in organelle acidification, and V-ATPase activity is regulated by reversible disassembly in many different settings. Using the yeast Saccharomyces cerevisiae as a replicative aging model, we demonstrate that V-ATPases disassemble into their V(1) and V(0) subcomplexes in aging cells, with release of V(1) subunit C (Vma5) from the lysosome-like vacuole...
Brain mechanical properties predict longitudinal cognitive change in aging and Alzheimer's disease
Age-related cognitive decline is a complex phenomenon that is influenced by various neurobiological processes at the molecular, cellular, and tissue levels. The extent of this decline varies between individuals and the underlying determinants of these differences are not fully understood. Two of the most prominent signs of cognitive decline in aging are the deterioration of episodic memory, which is a hallmark of Alzheimer's disease (AD), and the nearly always accompanying atrophy of the medial...
Housing Relocation and Residential Satisfaction After Relocation: Effects of Dwelling Condition Changes on Older Adults in the Community
BACKGROUND: This study seeks to analyze the trajectories of residential satisfaction among older adults before and after relocation and explore the variability in the relationship between relocation and residential satisfaction based on changes in housing conditions during the relocation process.
GD3 ganglioside checkpoints in immune surveillance of senescent cells
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Aging stem cells limit tumorigenesis
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Deep learning reveals diverging effects of altitude on aging
Aging is influenced by a complex interplay of multifarious factors, including an individual's genetics, environment, and lifestyle. Notably, high altitude may impact aging and age-related diseases through exposures such as hypoxia and ultraviolet (UV) radiation. To investigate this, we mined risk exposure data (summary exposure value), disease burden data (disability-adjusted life years (DALYs)), and death rates and life expectancy from the Global Health Data Exchange (GHDx) and National Data...
Lung endothelial cell senescence impairs barrier function and promotes neutrophil adhesion and migration
Cellular senescence contributes to inflammation and organ dysfunction during aging. While this process is generally characterized by irreversible cell cycle arrest, its morphological features and functional impacts vary in different cells from various organs. In this study, we examined the expression of multiple senescent markers in the lungs of young and aged humans and mice, as well as in mouse lung endothelial cells cultured with a senescence inducer, suberoylanilide hydroxamic acid (SAHA),...
Seeking optimal non-pharmacological interventions for sarcopenia: a systematic review and network meta-analysis
CONCLUSION: Resistance exercise (low-moderate load), exercise plus nutrition, and nutritional supplementation (fatty acids, etc.) may be protective against sarcopenia. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=474799 , ID: CRD4202347479.
Burden of caregivers of older people in Sri Lanka: an overlooked concern in the health care system
CONCLUSION: The Sinhala version of the BSFC-s demonstrated strong reliability and validity, making it a suitable tool for assessing caregiver burden in Sri Lanka. Most caregivers reported high levels of subjective burden, particularly those with lower socio-demographic status.
Gene therapy ameliorates bowel dysmotility and enteric neuron degeneration and extends survival in lysosomal storage disorder mouse models
Children with neurodegenerative disease often have debilitating gastrointestinal symptoms. We hypothesized that this may be due at least in part to underappreciated degeneration of neurons in the enteric nervous system (ENS), the master regulator of bowel function. To test this hypothesis, we evaluated mouse models of neuronal ceroid lipofuscinosis type 1 and 2 (CLN1 and CLN2 disease, respectively), neurodegenerative lysosomal storage disorders caused by deficiencies in palmitoyl protein...
Dimensional engineering of interlayer for efficient large-area perovskite solar cells with high stability under ISOS-L-3 aging test
The utilization of low-dimensional perovskites (LDPs) as interlayers on three-dimensional (3D) perovskites has been regarded as an efficient strategy to enhance the performance of perovskite solar cells. Yet, the formation mechanism of LDPs and their impacts on the device performance remain elusive. Herein, we use dimensional engineering to facilitate the controllable growth of 1D and 2D structures on 3D perovskites. The differences of isomeric ligands in electrostatic potential distribution and...
SMARCA4 regulates the NK-mediated killing of senescent cells
Induction of senescence by chemotherapeutic agents arrests cancer cells and activates immune surveillance responses to contribute to therapy outcomes. In this investigation, we searched for ways to enhance the NK-mediated elimination of senescent cells. We used a staggered screen approach, first identifying siRNAs potentiating the secretion of immunomodulatory cytokines to later test for their ability to enhance NK-mediated killing of senescent cells. We identified that genetic or...
Plasma Proteomic Signature as a Predictor of Age Advancement in People Living With HIV
Due to the increased burden of non-AIDS-related comorbidities in people living with HIV (PLHIV), identifying biomarkers and mechanisms underlying premature aging and the risk of developing age-related comorbidities is a priority. Evidence suggests that the plasma proteome is an accurate source for measuring biological age and predicting age-related clinical outcomes. To investigate whether PLHIV on antiretroviral therapy (ART) exhibit a premature aging phenotype, we profiled the plasma proteome...
Centromere inactivation during aging can be rescued in human cells
Aging involves a range of genetic, epigenetic, and physiological alterations. A key characteristic of aged cells is the loss of global heterochromatin, accompanied by a reduction in canonical histone levels. In this study, we track the fate of centromeres in aged human fibroblasts and tissues and in various cellular senescent models. Our findings reveal that the centromeric histone H3 variant CENP-A is downregulated in aged cells in a p53-dependent manner. We observe repression of centromeric...
Clonally expanded, targetable, natural killer-like NKG7 T cells seed the aged spinal cord to disrupt myeloid-dependent wound healing
Spinal cord injury (SCI) increasingly affects aged individuals, where functional impairment and mortality are highest. However, the aging-dependent mechanisms underpinning tissue damage remain elusive. Here, we find that natural killer-like T (NKLT) cells seed the intact aged human and murine spinal cord and multiply further after injury. NKLT cells accumulate in the spinal cord via C-X-C motif chemokine receptor 6 and ligand 16 signaling to clonally expand by engaging with major...
The TRPV1-PKM2-SREBP1 axis maintains microglial lipid homeostasis in Alzheimer's disease
Microglia are progressively activated by inflammation and exhibit phagocytic dysfunction in the pathogenesis of neurodegenerative diseases. Lipid-droplet-accumulating microglia were identified in the aging mouse and human brain; however, little is known about the formation and role of lipid droplets in microglial neuroinflammation of Alzheimer's disease (AD). Here, we report a striking buildup of lipid droplets accumulation in microglia in the 3xTg mouse brain. Moreover, we observed significant...
Analysis of sex-specific disease patterns associated with human lifespan
Disability and multimorbidity increase with aging and constitute a challenge for the health system. However, different individuals display different aging trajectories, and understanding the underlying relationships between lifespan and disease is fundamental for identifying the different patterns in human lifespan. A previous study explored associations between lifespan and age of onset of diseases of different organ systems, prevalence of escapers, and percentage of life free of disease...
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