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Lipid Droplet-Driven Ribosome Collisions Trigger ZAKalpha-p38 Signaling to Accelerate Testicular Aging
Testicular aging, a key feature of late-onset hypogonadism (LOH), is closely associated with Sertoli cells dysfunction. Emerging evidence implicates lipid droplet (LD) accumulation as a hallmark of aging in Sertoli cells, but its role in Sertoli cells senescence and the associated molecular mechanisms are unknown. We found that aging and obesity drove progressive LD accumulation in Sertoli cells, accompanied by mitochondrial dysfunction and ROS overproduction. Palmitic Acid (PA)-induced LD...
Investigations on the effects of SH2B2 on Parkinson's disease based on its in vivo and in vitro neurotoxic model
Parkinson's disease (PD) is characterized by dopaminergic neuron loss, motor dysfunction, and Lewy body formation. Src homology 2B adaptor protein 2 (SH2B2), a member of the SH2B family with known roles in neuroregulation, has not been fully explored in PD. This study aimed to investigate the neuroprotective effects and mechanisms of SH2B2 in PD. MPTP-induced mouse model and MPP^(+)-treated SH-SY5Y cell model were established to simulate PD in vivo and in vitro. Mice were randomly divided into...
Complex relationships among various domains of intrinsic capacity and their associated factors in community-dwelling older adults: A network analysis
CONCLUSIONS: IC, particularly in the domains of cognition and mobility, was prevalently impaired among older adults. We identified both common and domain-specific factors associated with IC, offering insights for developing targeted interventions to enhance IC.
The social microbiome of older people
The human gut microbiome (GM) is increasingly recognized as one of the main systems influencing the aging trajectory. Age-related dysbiosis, with imbalance between symbionts and pathobionts, can in fact fuel chronic inflammation (inflammaging) and promote frailty. In older individuals, GM composition is characterized by marked inter-individual variability and consistently influenced by environmental exposures. Studies conducted in animals and closed human communities suggest that social contacts...
Rejuvenating the aging gut by targeting senescence
No abstract
Shear stress governs hematopoietic stem cell fate to promote inflammation-induced aging
Hematopoietic stem cells (HSCs) reside in the bone marrow in a quiescent state, but can be mobilized into the blood in response to inflammation, cytokine stimulation, nervous activity or hypoxia. Chronic inflammation, a hallmark of aging, accelerates HSC aging by promoting myeloid-biased differentiation and reducing self-renewal capacity, yet the role of mechanical stimulation in regulating these processes remains poorly understood. Here, we found that PIEZO1 senses shear stress in blood flow to...
Shared and specific blood biomarkers for multimorbidity
Aging is accompanied by the progressive accumulation of biological deficits, which increases susceptibility to developing multiple chronic diseases (that is, multimorbidity). The biological underpinnings of multimorbidity remain poorly understood. Here we analyzed 54 blood biomarkers reflecting inflammatory, vascular, metabolic and neurodegenerative processes in 2,247 individuals aged 60 and over from the Swedish National Study on Aging and Care in Kungsholmen. Multimorbidity was assessed using...
TGFβ signaling mediates microglial resilience to spatiotemporally restricted myelin degeneration
Microglia survey and regulate central nervous system myelination during embryonic development and adult homeostasis. However, whether microglia-myelin interactions are spatiotemporally regulated remains unexplored. Here, by examining spinal cord white matter tracts in mice, we determined that myelin degeneration was particularly prominent in the dorsal column (DC) during normal aging. This was accompanied by molecular and functional changes in DC microglia as well as an upregulation of...
Age-independent and targetable transcription factor networks regulating CD8(+) T cell senescence in aging humans
The age-related decline in immunity is accompanied by the accumulation of senescent CD8^(+) T cells. Using senescent cell isolation coupled with multi-omics profiling, we reveal the transition to senescence to be controlled by chromatin state-specific transcription factor (TF) networks in younger and older donors independent of age. These TF networks mediate widespread enhancer remodeling, repressing cell identity genes while upregulating inflammatory and secretory pathways. Inhibition or...
Cerebellar Purkinje cell firing reduction contributes to aging-related declining motor coordination in mice
Aging is associated with the decline of many bodily functions including motor coordination. Aging-related impairment in motor coordination can result in falls, which reduce independence, health span, and quality of life in the elderly. To study the neural mechanisms that underlie this decline, we studied aged mice and observed a progressive decline in motor coordination on multiple motor coordination assays. The cerebellum is critically involved in motor coordination and balance, and cerebellar...
Identifying direct risk factors in UK Biobank via simultaneous Bayesian-frequentist model-averaged hypothesis testing using Doublethink
Big data approaches to discovering nongenetic risk factors have lagged behind genome-wide association studies that routinely uncover novel genetic risk factors for diverse diseases. Instead, epidemiology typically focuses on candidate risk factors. Since modern biobanks contain thousands of potential risk factors, candidate approaches may introduce bias, inadequately control for multiple testing, and overlook important signals. Doublethink, a model-averaged hypothesis testing approach, offers a...
DMTF1 up-regulation rescues proliferation defect of telomere dysfunctional neural stem cells via the SWI/SNF-E2F axis
Impaired neural stem cell (NSC) proliferation/activation is associated with brain aging, but the underlying mechanisms remain poorly understood. Here, we unexpectedly find that DMTF1, a transcription factor that regulates the Arf/p53 axis in cancer, is down-regulated in the NSCs of a premature aging model driven by telomerase deficiency. DMTF1 up-regulation was able to rescue the impaired proliferation of telomere dysfunctional NSCs. Mechanistically, DMTF1 regulates the transcription of Arid2...
Perturbation of NAD(P)H metabolism with the LbNOX xenotopic tool extends lifespan and mitigates age-related changes
Aging involves widespread metabolic dysregulation, including a decline in total nicotinamide adenine dinucleotide (NAD) levels. While NAD precursor supplementation elevates total NAD levels, it does not reveal tissue-specific effects of an altered NADH [reduced form of NAD^(+) (oxidized NAD)]/NAD^(+) balance. To address this, we generated transgenic Drosophila expressing the genetically encoded xenotopic enzyme LbNOX, which converts NADH to NAD^(+). LbNOX expression modulated both NAD(H) and...
Primary Care Trainees Learn to Support Aging in Place Through a Virtual Area Agency on Aging Practicum
No abstract
Systemic LINE-1 RNA in Plasma Extracellular Vesicles Drives Neuroinflammation and Cognitive Dysfunction via cGAS-STING Pathway in Aging
Aging is characterized by systemic inflammation and progressive cognitive decline, yet the molecular pathways linking peripheral aging signals to central nervous system dysfunction remain elusive. Here, we identify plasma extracellular vesicle (EV)-derived long interspersed nuclear element-1 (LINE-1) RNA as a potent systemic aging factor mediating neuroinflammation and cognitive impairment in humans and mice. Plasma EV LINE-1 RNA levels markedly increase with age and strongly correlate with...
Shear stress governs hematopoietic stem cell fate to promote inflammation-induced aging
Linking single-cell multiomics with GWAS to reveal key regulators of disease risk
Squishing, squeezing and stretching age hematopoietic stem cells
Rejuvenating the aging gut by targeting senescence
As deep-sea mining race ramps up, mission will assess whether ecosystems recover afterward
A new series of research cruises will study rare abyssal species in areas slated for mining