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A surprising gut-heart connection may help explain why sleep apnea increases the risk of cardiovascular disease. In mice, disabling a bile acid receptor called FXR sharply reduced plaque buildup, opening the door to potential new treatments based on gut microbes and their chemical signals.

DNA from ground squirrel coprolites offers an unusually detailed record of ice age ecosystems

Tea may help protect against heart disease, diabetes, cancer, cognitive decline, and age related muscle loss, according to a major review. But the way you drink it matters, since bottled and bubble teas often contain ingredients that can diminish tea's health benefits.

Altered astrocyte-microglia interactions have been implicated in the pathogenesis of Alzheimer's disease, but the underpinning mechanisms remain unclear. Zhang and colleagues show that astrocytic PAD2-mediated citrullination of vimentin activates microglia, worsens Aβ accumulation, and exacerbates cognitive deficits. These findings highlight astrocyte-microglia crosstalk as a potential therapeutic target for Alzheimer's disease.

Mitochondrial DNA (mtDNA)-driven innate immune signaling sustains chronic neuroinflammation in neurological diseases such as Alzheimer's disease (AD), yet how this pathway is regulated in microglia remains poorly understood. Here, we identify the histone acetyltransferase KAT7 (HBO1) as a central epigenetic regulator that links chromatin remodeling to mitochondrial immune activation. KAT7 and its histone mark H3K14ac are elevated in microglia from 5×FAD mice and human AD brains. Integrative...

The perivascular glymphatic system promotes cerebrospinal fluid-interstitial fluid (CSF-ISF) interaction and macromolecular waste clearance and is an important determinant of brain homeostasis, the performance of which deteriorates with age. Astrocyte biology, vascular integrity, and age-associated cerebrovascular dynamic alterations interfere with the polarization of aquaporin-4 (AQP4) water channels on astrocytic endfeet, decreasing the clearance of aggregation-prone proteins, such as...

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promise in preclinical models of neurodegeneration, with emerging evidence suggesting these effects may be driven by modulation of neuroinflammation. However, the cellular mechanisms underlying GLP-1RA effects on neuroinflammation remain poorly understood. Here we show, using a mouse model of lipopolysaccharide-induced neuroinflammation, how semaglutide coordinates cellular responses to resolve neuroinflammation. We find that...

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Alzheimer's disease (AD) is a devastating neurodegenerative disorder marked by progressive cognitive decline. Metabolic disruptions are widely observed, yet their involvement in the molecular aetiology of AD remains underexplored. Here we identify hyperglycosylation as a driver of AD. Integrating spatial metabolomics, lipidomics and glycomics in transgenic AD mouse models and post-mortem human AD samples, along with advanced spatial isotopic tracing pulse-chase analysis of N-linked glycans, we...

Preservation of host fitness is a common feature of longevity and immunity to infection. In this issue of Immunity, Triana-Martinez et al. reveal that p16^(High) senescence-associated immune cells promote disease tolerance and healthy aging. Mechanistically, this is dependent on Toll-like receptor 7 (TLR7) and stimulator of interferon genes (STING) innate immune signaling controlling adenosine concentrations.

All immune cells engage in cholesterol metabolism, which generates a spectrum of bioactive metabolites that mainly include cholesterol itself, its biosynthetic intermediates, and oxidized or sulfated derivatives. These metabolites regulate not only cellular metabolism but also immune signaling. In addition, several functional proteins within cholesterol metabolic pathways exert non-canonical signaling functions that shape immune cell responses. Distinct immune cell types adopt specialized...

The perivascular glymphatic system promotes cerebrospinal fluid-interstitial fluid (CSF-ISF) interaction and macromolecular waste clearance and is an important determinant of brain homeostasis, the performance of which deteriorates with age. Astrocyte biology, vascular integrity, and age-associated cerebrovascular dynamic alterations interfere with the polarization of aquaporin-4 (AQP4) water channels on astrocytic endfeet, decreasing the clearance of aggregation-prone proteins, such as...

Brain aging is associated mainly with a decline in cognitive function and is a major risk factor for various neurodegenerative disorders (NDDs). Major hallmarks of aging include oxidative stress, chronic neuroinflammation, mitochondrial dysfunction, and impaired proteostasis. Although caloric restriction (CR) has consistently demonstrated neuroprotective effects, its long-term effects in humans remain challenging. Consequently, CRMs such as metformin, spermidine, and curcumin have been widely...

Cancer is increasingly relevant to ageing societies, yet progress in cancer control is difficult to assess when population years of life lost (YLL) to cancer appear stable. Using Danish registers, we followed 4.26 million residents aged ≥50 years (1980-2019) and estimated YLL under observed and counterfactual scenarios, separating demography and incidence from post-diagnosis outcomes. From the 1980s to the 2010s, YLL per individual changed little (men 2.3 to 2.1; women 2.5 to 2.2), while YLL per...

Aging is a complex multifactorial process that affects cellular function and tissue homeostasis over time. Despite substantial research, the molecular mechanisms driving cellular aging remain poorly understood. Many studies focused on changes in DNA methylation as an indicator of aging. In particular, methylation at polycomb CpG islands was shown to be predictive of phenotypic changes associated with aging. Since many age-related pathological processes are thought to originate from single cells,...

Aging is accompanied by progressive physiological decline and an increased risk of chronic disease, motivating the search for interventions that promote healthy longevity. We found that mid-life administration of Corylin, a flavonoid derived from Psoralea corylifolia, improves metabolic function, muscle integrity, and physical performance in mice maintained on a standard diet. Corylin significantly extends median lifespan in female mice, with an 11.9% increase and a 33% higher survival rate at...

Chronic inflammation drives vascular aging and stroke risk, yet circulating proteins linking immune activation to cerebrovascular events remain elusive. People with HIV (PWH) face elevated stroke risk beyond traditional vascular risk factors, even under antiretroviral therapy. We aimed to identify circulating proteomic signatures of HIV-associated stroke, characterize underlying biological pathways, and assess their longitudinal stability. We conducted a nested case-control study of 135 PWH with...

Different species age in similar ways but their lifespans differ by orders of magnitude. It is not clear how these similarities and differences arise from the accumulation of damage that underlies aging. Does long lifespan arise from reduced damage production, increased removal or enhanced robustness to damage? Here we apply the saturating removal model-a stochastic model of damage accumulation and removal-and fit it to survival data from well-studied species. Several parameters have...

How the small intestine ages at the cellular and molecular level has been unclear. Here we profile single nuclei from young and aged primate small intestine and find that aging brings barrier dysfunction, chronic inflammation and a shift in stem cell differentiation away from absorptive cells toward secretory cells. Through integrative multimodal analysis, we identify the transcriptional corepressor NCoR1 as a key player whose decline is conserved in the aging human gut. In human intestinal...

Nucleotides-essential substrates for DNA repair, energy metabolism, and redox regulation-are emerging as nutritional modulators of biological aging. Yet, individual responses to exogenous nucleotide (NTs) supplementation remain poorly understood. Given that urate metabolism governs systemic oxidative balance, this study investigated whether genetic variability in urate regulation modifies the anti-aging effects of NTs. In this secondary analysis of the TALENTs randomized controlled trial (121...