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The relationship between epigenetic age acceleration (EAA) and midlife cognitive function remains unclear, with limited causal evidence. We investigated this association in 1252 Black and White middle-aged adults from the Bogalusa Heart Study (BHS) and conducted a two-sample Mendelian randomization (MR) analysis using GWAS summary statistics for EAA (N = 34,710) and cognition (N ≤ 106,162). In BHS, higher Hannum age acceleration, PhenoAge acceleration, and GrimAge acceleration (GrimAA) were each...

Cartilaginous fishes (e.g., sharks, rays, and skates) cannot see blue or violet light, potentially because they lack the shortwave-sensitive cone opsin gene (sws). Widespread gene loss can occur during evolution, but the evolutionary mechanisms underlying sws loss remains unclear. Here, we construct whole-genome assemblies of Okamejei kenojei (skate) and Prionace glauca (blue shark). We then analyze the distribution characteristics and intragroup differences of opsin-related genes in...

Acute kidney injury (AKI) can lead to chronic kidney disease (CKD), a transition driven by cellular senescence, a state of irreversible cell-cycle arrest. However, the molecular mechanisms promoting this pathological process remain unclear. Here we show that the channel protein Pannexin1 (Panx1) promotes this detrimental senescence and subsequent kidney fibrosis. We found that Panx1 functions in a noncanonical role as a calcium (Ca^(2+)) leak channel within the endoplasmic reticulum (ER), a key...

We present direct sequencing methodologies, scTAPS for 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) and scCAPS + specifically for 5hmC, enabling quantitative detection of 5mC and 5hmC at single-base resolution and single-cell level. Achieving approximately 90% mapping efficiency, our plate-based methods accurately recover 5mC and 5hmC profiles in CD8 + T and mouse embryonic stem cells. Notably, scCAPS + reveals a global increase in 5hmC across neuronal and non-neuronal cells in the...

The concept of cognitive reserve explains how the brain maintains function despite age-related changes or neuropathological damage. Factors such as education, cognitive stimulation, and physical activity contribute to strengthening this reserve. While research has highlighted the benefits of structured exercise, less attention has been given to the impact of incidental physical activity (IPA) everyday, unplanned movements like walking or household chores. This study examined the relationship...

CONCLUSION: Our results reveal less activation of the task-relevant areas in participants from Okinawa as compared to Dutch participants. It could be hypothesized, with caution, that Okinawan older adults may need less executive processing resources to perform the task. Other differences in activation may be related to different strategy use, which may be studied in more detail in future investigations.

Patterns of brain aging are generally conserved among primates; however, there is marked variation in the observed rate among individuals, species, and brain regions. The hippocampus is a region particularly susceptible to the aging process. To better understand how the hippocampus changes over the lifespan, we measured gene expression in 96 banked hippocampus samples from adult male and female rhesus macaques aged 3-35 years old. Importantly, our dataset included representation across adulthood...

Sodium chloride (NaCl) is an essential nutrient, but it is toxic in excess. In humans, excessive dietary NaCl can cause high blood pressure, which contributes to age-related diseases, including stroke and heart disease. We used Caenorhabditis elegans to elucidate how NaCl levels influence animal aging. Most experiments on this animal are conducted in standard culture conditions: Nematode Growth Medium (NGM) agar with a lawn of E. coli. Here, we report that the supplemental NaCl in standard NGM,...

Beyond their classical roles in hemostasis and coagulation, accumulating evidence highlights platelets as multifaceted regulators within the nervous system. Research has revealed that platelet-derived factors promote blood-brain barrier (BBB) maturation and angiogenesis via neurochemical pathways. At the same time, platelet-rich plasma (PRP) facilitates neural regeneration by mitigating the neurotoxicity of amyloid-beta (Aβ) and activating the PI3k/Akt signaling pathway. Platelets also modulate...

Normal aging is associated with decline in dopamine function. Factors associated with individual differences in dopamine decline rates remain unclear but are important to map to spare dopamine-related functions, such as cognition. Here we focused on manifestations of cerebral small-vessel disease from magnetic resonance imaging (white-matter lesions, lacunes, and perivascular space dilation) and vascular risk factors (e.g., hypertension, body mass index (BMI), and hyperlipidemia). We assessed...

Sarcopenia is characterized by aging-related progressive loss of muscle mass and function; however, the specific and sensitive biomarkers are still limited. Biometals and trace elements provide a potential connection linking the environment and lifestyle to pathological processes of sarcopenia. The aim of the present study was to investigate the relationship between urinary trace elements levels and the presence of sarcopenia. A total of 100 older adults aged ≥65 years consisting of 50 patients...

CONCLUSION: ABLE demonstrated the feasibility of recruiting biologically older yet generally healthy middle-aged adults for gerotherapeutic interventions.