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Mild mitochondrial stress could extend lifespan across species, yet the underlying mechanism remains unclear. Here, we show that inhibition of mitochondrial respiration induces a sustained transcriptional program that enhances lysosomal proteolysis during aging in Caenorhabditis elegans. Mechanistically, this response is primarily regulated by the intestinal GATA transcription factor ELT-2, which retains high expression and directly binds to GATA motifs in the promoters of lysosomal protease...

Resting-state electroencephalography (EEG) provides a sensitive measure of large-scale neural dynamics and has been widely used to characterize age-related changes in brain function. However, many prior studies have relied on relatively small samples or single-condition recordings, limiting the generalizability of findings. In this study, we investigated normative age-related trajectories of EEG spectral features across eyes-closed (EC) and eyes-open (EO) conditions in a large cohort of healthy...

CONCLUSION: This study delineates two IC profiles among Chinese older adults. The XGBoost-based model was explored for rapid IC profile classification. These findings highlight heterogeneity in IC and support the feasibility of a simplified digital approach, with external validation warranted.

CONCLUSION: This study shows that the presence of MASLD is significantly associated with an increased risk of a worse depression trajectory. In subgroup analysis, this relationship was particularly pronounced amongst females and among individuals with key cardiometabolic morbidities such as dyslipidaemia.

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Myeloid cells, including microglia and perivascular macrophages, are central to Alzheimer's disease (AD) neurobiology, yet their role remains incompletely understood. We profiled 832,505 human myeloid cells from the prefrontal cortex of 1,607 donors spanning the lifespan and showing varying degrees of AD neuropathology. We delineated six subclasses comprising 13 transcriptionally distinct subtypes and identified adaptive changes associated with aging and AD progression. Here we show that a...

Epidemiological links between cognition and body physiology in aging are well established, but their strength and drivers remain unclear. Which physiological systems - from body composition to cardiovascular, pulmonary, renal, hepatic, immune, metabolic, and musculoskeletal - best predict cognition, and to what extent are cognition-body associations linked to brain variation across aging? We examined 19 physiological phenotypes alongside three neuroimaging modalities in over 30,000 UK Biobank...

Myeloid cells, including microglia and perivascular macrophages, are central to Alzheimer's disease (AD) neurobiology, yet their role remains incompletely understood. We profiled 832,505 human myeloid cells from the prefrontal cortex of 1,607 donors spanning the lifespan and showing varying degrees of AD neuropathology. We delineated six subclasses comprising 13 transcriptionally distinct subtypes and identified adaptive changes associated with aging and AD progression. Here we show that a...