Aging & Longevity

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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.

The Cambridge Centre for Ageing and Neuroscience (Cam-CAN, www.cam-can.org ) was established 15 years ago to investigate the cognitive and brain bases of healthy adult ageing. Demographic, health and lifestyle data, cognitive data and a wide range of brain imaging data, were shared with other researchers around the world, resulting in many scientific findings. Here we review these findings under the broad headings of 'neuroscience of ageing', 'methodological developments' and...

The mechanisms regulating transcriptional changes during brain aging remain poorly understood. Here, we use single-cell epigenomics to profile chromatin accessibility and gene expression across eight mouse brain regions at 2, 9, and 18 months of age. In addition to a marked decline in progenitor populations involved in neurogenesis and myelination, we observe widespread and concordant age-associated changes in transcription and chromatin accessibility across both neuronal and glial cell types....

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...

Astrocyte endfeet form a near-continuous sheath around the brain's vasculature, defining the perivascular spaces (PVS) that are crucial for brain fluid flow and solute transport. Yet, their precise physiological role remains poorly understood. Using 3D electron microscopy data, we created a high-fidelity poroelastic computational model of an arteriole segment with surrounding endfeet and parenchyma to investigate tissue displacement and fluid flow within the PVS, endfeet, and extracellular space...

Controlling the structure and function of colloidal gels requires a detailed understanding of how the various components govern network formation and aging. In particular, molecular additives like salts are widely used to tune interparticle interactions, yet their influence on gelation pathways in complex systems such as colloidal nanocrystal gels remains inadequately understood. Here, we investigate how noncoordinating salts modulate the evolution of gels formed using chemically linked...

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Biomarkers of ageing are defined as age-related changes in body function or composition that could serve as a measure of 'biological' age and predict the onset of age-related diseases and/or residual life expectancy. We conducted the MARK-AGE Study, a European population study (3300 subjects aged 35-74) to identify a powerful set of biomarkers of ageing. A total of 362 clinical-chemistry, genetic, cellular or molecular biomarkers were analysed for each subject. Using statistical models as well...