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The protein-level functionalities of the human gut microbiota in large populations, and their associations with host factors, remain unexplored. This study reports a metaproteomic study of 1,967 fecal samples from 1,399 middle-aged and elderly Chinese individuals, identifying microbial functions linked to 44 phenotypes. We uncover aging-associated functional shifts in carbon metabolism and energy production driven by species within the Bacillota, Bacteroidota, Actinomycetota, and Pseudomonadota....

Lactate, once viewed merely as a glycolytic byproduct, is now recognized as a key signaling molecule and epigenetic regulator through the recently identified post-translational modification known as lactylation. In diabetic microvascular complications, including diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic peripheral neuropathy (DPN), persistent hyperglycemia promotes metabolic reprogramming toward glycolysis and leads to excessive lactate production. This sustained...

Type 1 diabetes, particularly with childhood onset, is associated with altered neurocognitive traits, yet the underlying biological mechanisms are unclear. Here, we integrate genome-wide association results with single-cell epigenomic profiles and show that type 1 diabetes heritability is enriched in accessible chromatin of human brain-resident cells, most notably microglia, across neurodevelopment into adulthood. Bonferroni-corrected cross-trait genetic correlation analyses reveal negative...

Aging is the strongest risk factor for chronic diseases such as cardiovascular disease, Alzheimer's, and cancer. DNA methylation (DNAm) clocks offer a promising measure of biological age, but most rely on linear models that miss non-linear dynamics and CpG interactions. To address this, we developed a deep neural network (DNN)-based DNAm clock trained on 29,167 samples profiled on Illumina EPIC v1.0 and v2.0 arrays. Using 12,234 CpGs selected through sex- and age-stratified correlations, our...

Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD) but its neural mechanisms remain poorly understood. A mechanistic understanding requires precise characterization of functional responses to various stimulation conditions within the same individual. Here we use 3-T magnetic resonance imaging (MRI)-compatible DBS and precision imaging to collect extensive data from 14 patients with PD who received DBS. Across five timepoints spanning 1 year, each patient...

The connection between aging and immune dysfunction is uncovering how immunoaging processes contribute to disease. Recent data from Alzheimer’s disease, Parkinson’s disease, and adult and pediatric glioblastomas reveal a novel role for TIM3 in brain immune alteration. These findings highlight the role of TIM3 in promoting myeloid cell dysfunction toward an immunosuppressive profile. TIM3-blocking antibody treatments for central nervous system pathologies could be a new therapeutic window for...

Mitochondrial diseases progressively lead to multisystemic failure with treatment options remaining extremely limited. Here, to investigate strategies that alleviate mitochondrial dysfunction, we first generate a ubiquitous and tamoxifen-inducible knockout mouse model of mitochondrial transcription factor A (TFAM), a nuclear-encoded protein involved in mitochondrial DNA (mtDNA) maintenance - Tfam^(fl/fl)Ubc^(Cre-ERT2) (iTfamKO) mice. Systemic TFAM deficiency triggers mitochondrial decline in a...

Aging is the strongest risk factor for chronic diseases such as cardiovascular disease, Alzheimer's, and cancer. DNA methylation (DNAm) clocks offer a promising measure of biological age, but most rely on linear models that miss non-linear dynamics and CpG interactions. To address this, we developed a deep neural network (DNN)-based DNAm clock trained on 29,167 samples profiled on Illumina EPIC v1.0 and v2.0 arrays. Using 12,234 CpGs selected through sex- and age-stratified correlations, our...

Emerging evidence shows that inflammaging varies across populations, challenging universal immune-aging models. Urbanization in sub-Saharan Africa-characterized by reduced exposure to infectious diseases and rising rates of noncommunicable diseases-offers a natural experiment for assessing environmental effects on inflammaging. Lower inflammaging in indigenous groups may reflect adaptation to chronic infection, whereas heightened inflammation in industrialized populations suggests ecological...

Epigenetic clocks derived from DNA methylation patterns are among the most promising biomarkers of biological aging^(1-7), as they capture molecular signatures that predict morbidity and mortality beyond chronological age. Although cross-sectional assessments of epigenetic age have been linked consistently to health outcomes and lifespan, it remains unclear whether the rate of change in these clocks over time provides additional insight into aging trajectories. In this longitudinal study of 699...

CONCLUSIONS: The study highlighted the beneficial role of DASH diet adherence and sustainable nutritional practices in mitigating depressive symptoms and supporting cognitive function in older adults. These dietary patterns could represent crucial components of preventive strategies for healthy aging. Further longitudinal research using objective dietary assessments is needed to clarify causal relationships.

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Vascular stiffness and aging are critical contributors to cardiovascular diseases. Whether betulinic acid (BA), a natural triterpenoid, alleviates vascular aging remains unclear. Mouse aortic smooth muscle cells (MASMCs) with oleic acid (OA)-induced lipotoxic senescence were treated with BA (30 μM). Transcriptomic analysis and functional assays were conducted. In vivo, ApoE^(-/-) mice fed a high-fat diet received oral BA (25 mg/kg/day) for 14 weeks. OA-induced lipotoxic senescence was associated...

TrAEL-seq is a robust method for profiling DNA replication genome-wide that works in unsynchronized cells and does not require drugs or nucleotide analogues. Here, we provide an updated method for TrAEL-seq that improves sample quality and includes multiplexing of up to six samples which dramatically improves throughput, and we validate TrAEL-seq in multiple mammalian cell lines. The updated protocol is straightforward and robust yet provides excellent resolution comparable to OK-seq in...

DNA methylation is a key regulatory mechanism reflecting both short- and long-term biological stimuli. While it has been widely used to study aging through disease-associated methylation shifts, its potential for revealing tissue-specific shifts remains underexplored due to the lack of comprehensive reference atlases with correspondingly systematic analysis framework. To address this, we assemble the largest and most diverse atlas of healthy human tissue and cells profiled by 450K arrays,...

Population aging accelerates globally, increasing sleep-related complaints among older adults. These disorders substantially impact cognitive function, physical health, and quality of life. This narrative review examines age-related changes in sleep architecture, alterations in circadian rhythm, common sleep disorders, and modifiable behavioral factors in older populations. We searched PubMed, Web of Science, and Google Scholar through December 2025 for studies involving adults aged ≥ 65 years...

CONCLUSIONS AND IMPLICATIONS: Sarcopenia, regardless of severity, was associated with frailty progression in Chinese older adults, thereby identifying it as a key factor linked to frailty progression. These findings support early screening and targeted interventions to facilitate healthy aging.

CONCLUSIONS AND IMPLICATIONS: Higher preadmission LTCI CNL was associated with an increased risk of all-cause mortality after discharge in older patients hospitalized for stroke. LTCI CNL may serve as a practical indicator for identifying patients at high mortality risk. Understanding how pre-stroke functional status influences long-term survival may provide valuable information for early clinical decision making in stroke treatment.

Neurofibrillary tangles (NFTs) formed from the protein tau disrupt neuronal function in Alzheimer's disease and are strongly associated with cognitive decline. Early events in tau aggregation are increasingly linked to the formation of biomolecular condensates, which lower the energetic barriers to pathological aggregation by acting as intermediates that transition into insoluble assemblies, a mechanism also implicated in other neurodegenerative diseases, such as amyotrophic lateral sclerosis...