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Defining Microbiota-Derived Metabolite Butyrate as a Senomorphic: Therapeutic Potential in the Age-Related T Cell Senescence

2 weeks ago
Advancing age is accompanied by an accumulation of senescent T cells that secrete pro-inflammatory senescence-associated secretory phenotype (SASP) molecules. Gut-microbiota-derived signals are increasingly recognised as immunomodulators. In the current study, we demonstrated that ageing and the accumulation of senescent T cells are accompanied by a reduction in microbial-derived short-chain fatty acids (SCFAs). Culturing aged T cells in the presence of butyrate suppresses the induction of a...
Nia Paddison Rees

Angiotensin II induces sex-specific ventricular remodeling in aging C57Bl/6 mice

2 weeks ago
Renin-angiotensin system (RAS) activation in heart failure (HF) increases circulating angiotensin II (AII). This increases blood pressure (BP) and promotes adverse ventricular remodeling that makes HF worse. Although human HF increases with age and differs between the sexes, preclinical studies have used young, mostly male animals. We investigated sex differences in AII-induced cardiac remodeling in aging C57BL/6 mice. Mice (≈16 months) were infused with AII (3 mg/kg/day; 6 weeks; osmotic...
Ninh Khuong

Association of muscle mass and strength with blood-based epigenetic aging among middle-aged and older adults in the United States

2 weeks ago
Muscle mass and strength influence various age-related health outcomes, however their individual and joint associations with biological aging remain understudied. This study investigated the associations of muscle health with epigenetic aging based on DNA methylation in blood samples, among middle-aged and older adults. We analyzed data from 1,121 individuals from the 1999-2002 cycles of the National Health and Nutrition Examination Survey. Muscle mass was assessed using the appendicular...
Hye-Ji Seo

Stressors-induced cognitive dysfunction during aging: mechanisms and future challenges

2 weeks ago
Stressful events can lead to transient impairments in learning and memory, a phenomenon more pronounced in the elderly. As global life expectancy rises, the shift toward an aging society underscores the urgent need for effective preventive strategies against stress-induced cognitive dysfunction. Elucidating its pathogenesis is essential for developing neuroprotective interventions and mitigating medical and societal impacts. In this study, male C57BL/6 mice aged 2 and 18 months were subjected to...
Yizhe Zhang

From variants to mechanisms: Neurogenomics in the post-GWAS era

2 weeks 1 day ago
Genome-wide association studies (GWASs) have identified thousands of variants associated with neuropsychiatric disorders (NPDs), including autism spectrum disorder (ASD), schizophrenia (SCZ), and Alzheimer's disease (AD). However, deciphering the "causal" biological mechanisms and pathways through which these variants act remains a major obstacle that hinders translational understanding of NPD pathogenesis. NPDs are highly polygenic with contributions from pleiotropic variants across the allelic...
Michael P Margolis

Age-(in)dependent altered molecular mechanisms in Parkinson's disease through extracellular vesicle proteome and lipidome

2 weeks 1 day ago
Parkinson's disease (PD) remains insidious and clinically elusive at early stages due to the lack of precise, non-invasive biomarkers. Given their ability to cross the blood-brain barrier, extracellular vesicles (EVs) offer a promising platform for biomarker discovery in neurodegeneration. Using an affinity-based EV isolation method, we profile EV proteomes and lipidomes from plasma across life stages, followed by targeted validation via parallel reaction monitoring (PRM). We identify both...
Yu-Ting Zhang

Molecular profiling of brain endothelial cell to astrocyte endfoot communication in mouse and human

2 weeks 1 day ago
Our understanding of how the body communicates with the brain to coordinate their functions is remarkably limited. At the blood-brain barrier (BBB), brain endothelial cells (BECs) are ideally positioned to mediate signaling between blood and brain parenchyma via direct communication with astrocyte perivascular processes (endfeet). We develop a method to define the mouse in vivo astrocyte endfoot proteome, which in combination with BEC-specific RNA-seq, reveal BEC to astrocyte endfoot...
Steven A Hill

Microglia modulate Abeta-dependent astrocyte reactivity in Alzheimer's disease

2 weeks 1 day ago
Experimental evidence suggests that activated microglia induce astrocyte reactivity in neurodegenerative disorders, such as Alzheimer's disease (AD). In this study, we investigated the association between microglial activation and amyloid-β (Aβ) with reactive astrogliosis in individuals across the AD spectrum. We examined 101 individuals using positron emission tomography radiotracers to assess Aβ deposition ([^(18)F]AZD4694), tau aggregation ([^(18)F]MK-6240) and microglial activation...
João Pedro Ferrari-Souza

Age-related auditory nerve deficits propagate central gain throughout the auditory system: Associations with cortical microstructure and speech recognition

2 weeks 1 day ago
There is growing evidence that perceptual difficulties associated with age-related hearing loss are not solely due to cochlear damage and are exacerbated by central nervous system changes. We examined electrophysiological (EEG) responses to clicks and diffusion kurtosis imaging in 49 older (29 female) and 26 younger (20 female) adults to determine the extent to which auditory nerve (AN) deficits in older adults contributed to functional and structural changes throughout the auditory system....
Emily M Fabrizio-Stover