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A recent study by Bieri et al. shows that exercise elevates hepatic glycosylphosphatidylinositol-specific phospholipase D1 (GPLD1), which cleaves endothelial tissue-nonspecific alkaline phosphatase (TNAP) to rejuvenate cerebrovascular signaling, enhance cognition in aging, and attenuate Alzheimer's-related pathology. This liver-to-brain enzymatic axis positions hepatokines as potent mediators of exercise-induced neuroprotection, which redefines systemic metabolism as a driver of brain...

Blood biomarkers are rapidly becoming established for Alzheimer's Disease (AD) diagnosis. However, there is a need for more scalable tools to reach the 99% of individuals with early cognitive impairment who are not seen in specialist healthcare services. A recent study validated a capillary blood sampling technique to detect the p-tau217 and GFAP biomarkers. Here we used our PROTECT research study to show that these biomarkers, when collected using self-administered fingerprick tests, correlate...

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A recent study by Bieri et al. shows that exercise elevates hepatic glycosylphosphatidylinositol-specific phospholipase D1 (GPLD1), which cleaves endothelial tissue-nonspecific alkaline phosphatase (TNAP) to rejuvenate cerebrovascular signaling, enhance cognition in aging, and attenuate Alzheimer's-related pathology. This liver-to-brain enzymatic axis positions hepatokines as potent mediators of exercise-induced neuroprotection, which redefines systemic metabolism as a driver of brain...

The Six1 (SIX homeobox 1) gene is pivotal in renal and pulmonary development and differentiation. Its dysregulation is implicated in oncogenesis and tumor progression via enhancing cell proliferation and delaying senescence. However, whether or how it functions in the natural aging have not been investigated. To answer this question, we generated Six1 gene knockout mice using CRISPR-Cas9 technology. All Six1 biallelic knockout mice died at birth since the underdeveloped lungs. In Six1^(+/-)...

The aging process exhibits tissue-specific characteristics, yet its underlying mechanisms remain poorly understood. While it is widely accepted that a reduction in blood vessels in hard tissues contributes to aging, such as in osteoporosis, the vascular changes driving soft tissue aging and degeneration remain unclear. Here, by integrating single-cell transcriptomics and light-sheet imaging, we uncover a striking infiltration of type H-like blood vessels and an aging-specific Coch^(+) cell...

Developing sustainable adhesives with simultaneous high adhesive strength and excellent work of debonding remains challenging. Here, strong, ultra-tough, environmentally reliable, and recyclable polyurethane adhesives are reported, utilizing a multiscale engineering approach. The multiscale structure employs a top-down design philosophy to merge the advantages of both thermoplastic and thermosetting systems, integrating multi-level organizations including macroscale dual-length dynamic...

Incentives modulate voluntary movement, yet the circuitry channeling these signals into motor output remains unclear. Classical models emphasize a closed-loop circuit (CLC) linking dorsal putamen (PUTd) with the motor cortex, but this pathway is anatomically segregated from affective processing regions. Anatomical and clinical evidence point to an alternative: an open-loop circuit (OLC) from ventral putamen (PUTv) that may route affective signals to the motor cortex. Here, we conducted two...

Red pulp macrophages (RPMs) remove senescent erythrocytes from the circulation and recycle their iron for erythropoiesis. The development of RPMs is guided by signals from the microenvironment, which promote expansion and tissue adaptation through the induction of transcription factors, including Spi-C and PPARγ. Here, we show that infection with the nematode Nippostrongylus brasiliensis or treatment with IL-33 results in the accumulation of activated group 2 innate lymphocytes (ILC2s) in the...

Background Pain is highly prevalent in older adults and linked to hyperacusis, yet evidence on its relationship with self-reported hearing difficulty (HD) remains limited. The aim of this study was to investigate the associations of pain with incident HD. Methods Adults aged ≥50 from six nationally-representative aging cohorts were included: the Health and Retirement Study (HRS), the English Longitudinal Study of Ageing (ELSA), the Survey of Health, Ageing and Retirement in Europe (SHARE), the...

The extended stay-green trait is beneficial to increase photosynthetic efficiency, thereby enhancing crop yield. However, factors and mechanisms affecting this process remain largely unknown. Here, we cloned a leaf precocious senescence gene (lps1-1) and created additional null alleles. All lps1 mutants exhibited accelerated leaf senescence with reduced chlorophyll contents and photosynthetic efficiency. The 100-kernel weight and storage reserve content were decreased in lps1 kernels, while the...

Over the past decade, clonal hematopoiesis (CH) has gained substantial attention as a prevalent, age-associated phenomenon with major implications for hematologic malignancy, cardiovascular disease, and mortality. CH arises from the clonal expansion of hematopoietic stem cells and progenitor cells harboring somatic mutations, most commonly in genes implicated in leukemia. Beyond chronological aging, CH evolution is shaped by lifelong exposure to inflammatory, metabolic, and environmental...

From a cellular perspective, senescence has been considered a binary state, wherein cells are either senescent or not. This reductionist notion, often defined as irreversible growth arrest, has guided efforts to identify universal biomarkers and senolytics, but both have consistently eluded us. This outcome is not surprising, given that the biological nature of senescence may not be strictly irreversible; the accumulated evidence suggests that growth arrest can become unstable over time, with...

Aging is a complex biological process characterized by progressive functional decline and increased risk of chronic diseases. In recent years, DNA methylation-based epigenetic clocks have emerged as some of the most robust biomarkers for estimating biological age. Initial research clocks, such as those developed by Horvath and Hannum, provided highly accurate chronological age predictions. Subsequent models, including PhenoAge, GrimAge, and DunedinPACE, improved upon this by incorporating...

Ryanodine receptors (RYRs) are ER-resident Ca² ^(+) -release channels enriched in excitable cells, including neurons. RYR hyperactivity is implicated in early pathogenesis of disorders such as Alzheimer's disease (AD), which is associated with impaired autophagy. We recently uncovered a mechanism linking RYR activity to lysosome availability for autophagy. RYRs localize to ER - lysosome contact sites via direct binding to ATP6V0A1, a V-ATPase subunit that also suppresses RYR-mediated Ca² ^(+)...

CONCLUSION: Different physical activity intensities were not significantly associated with resting-state functional connectivity of various brain networks in a sample of healthy older adults. This finding contrasts with the results of previous cross-sectional studies.

Stroke remains the second leading cause of death globally, yet traditional risk factors explain only 50-60 percent of cases. Emerging evidence indicates that lipid dysregulation is a central mechanism linking environmental exposures to cerebrovascular vulnerability. Aging, chronic inflammation, infections, diet, inactivity, stress, sleep disorders, and toxins are associated with disruption of lipid homeostasis through oxidative stress-induced lipid peroxidation, cytokine-mediated metabolic...