Aging & Longevity

Histone modifications represent an untapped resource for biological age prediction that overcomes limitations of traditional DNA methylation-based epigenetic clocks. Here, we developed and validated histone modification-based epigenetic clocks by systematically analyzing publicly available ChIP-seq datasets spanning six tissue types and six histone marks. We identified age-associated loci and constructed 36 tissue-specific epigenetic clocks that demonstrated strong resilience to technical and...

Infraslow (<0.1 Hz) global brain activity, quantified by the global mean blood-oxygenation-level-dependent (gBOLD) signal in resting-state functional magnetic resonance imaging (fMRI), is elevated during sleep and coupled to cerebrospinal fluid (CSF) dynamics, a key pathway for the brain waste clearance implicated in neurodegenerative disorders such as Alzheimer's disease. However, the effect of sleep deprivation on gBOLD activity and its interaction with aging remain poorly understood. Using a...

Parental age and inbreeding have both been shown to have substantial fitness effects in laboratory experiments and in observations of wild animals. These demographic effects are likely to be strongly impacted by habitat fragmentation and warming temperatures, so understanding them is a priority. In insects and other ectotherms, some processes implicated in senescence are dependent on temperature. Anticipated changes in climate may therefore have direct effects on senescence in insects, or...

Pharmacological modulation of ageing is viewed as a viable route to extending lifespan and healthspan, yet the efficacy of putative geroprotectors may depend strongly on physiological and environmental context. Lithium chloride (LiCl) has been reported to extend lifespan in several model organisms, but evidence remains inconsistent and the role of reproductive investment-an energetically costly and often lifespan-correlated process-has rarely been examined. We tested the effects of dietary LiCl...

Neurodegenerative diseases are a set of devastating medical conditions in which neuronal loss associated with the aggregation of toxic proteins leads to progressive cognitive impairment. These diseases are usually modeled in animals by mimicking late disease stages through genetic modifications that aggressively accumulate proteins that damage the brain. However, these diseases typically unfold over decades, and disease-associated genes are known to have important, but understudied, biological...

No abstract

Senescent mesenchymal stem cells residing in an inflammatory, dysbiotic, and hypoxic microenvironment pose a barrier to periodontal regeneration. Here we introduce a hydrocaffeic acid (HCA)-mediated silk fibroin hydrogel incorporating Mn/HCA-modified calcium peroxide (Mn-hCaO₂) and HCA-modified zeolitic imidazolate framework-8 (hZIF8) to rejuvenate this environment. The strategy imbues the hydrogel with enhanced adhesion and adaptability in periodontal pockets. The Mn-HCA complex acts...

Cellular interactions between thymocytes and other immune and stromal thymic cells play a key role in T cell maturation and homeostasis. Previous efforts delineating the cellular interactomes that support T cell development have mostly relied on imaging techniques, genetic deletion of essential molecular factors and bone marrow chimeras. Here, using synthetic NOTCH receptors we took a direct and unbiased genetic approach to fluorescently label cells in physical contact with CD4^(+) and...

Rising life expectancy and an aging population highlight the importance of cancer control. DNA methylation (DNAm)-based biological age (BA) may provide insights into aging, carcinogenesis, and cancer prevention and care. We estimated five BA metrics among 1916 participants aged 50-75 years at baseline in the German ESTHER cohort, with repeat BA measurements available for 894 participants after 8 years. Multivariable linear regression was used to assess associations between prior cancer and...

We reconceptualize p21 as the master regulator of a "resilience network" that empowers cancer cells to defy therapy. Beyond cell cycle arrest, p21 orchestrates a multi-faceted defense, suppressing ferroptosis and cuproptosis by governing redox and metal ion homeostasis. This perspective demands a therapeutic paradigm shift: targeting the p21 network is essential to dismantle this evolved survival machinery and force durable tumor regression in resistant cancers.

Large-scale randomized trials have found that multivitamin-multimineral (MVM) supplements and cocoa flavanols may benefit several age-related chronic conditions among older adults, but it remains unclear whether these two supplements directly slow the biological aging process. This prespecified ancillary study evaluated the 2-year effect of a daily MVM (Centrum Silver) and cocoa extract (500 mg cocoa flavanols per day, including 80 mg (-)-epicatechin) on five DNA methylation measures of...

Aging is associated with reduced cerebrovascular reactivity and impaired neurovascular coupling, limiting the brain's ability to maintain adequate oxygen delivery during physiological stressors such as hypoxia. These vascular changes may heighten middle-aged adults' vulnerability to hypoxia-induced neural and cognitive impairments, yet dose-response data integrating cerebral oxygenation and cognition remain scarce. In a single-blind, randomized crossover trial, 16 participants completed four...

Aging is a major contributor to β-cell dysfunction in type 2 diabetes, with cellular senescence increasingly recognized as an important underlying mechanism. Here, we established a doxorubicin (DOX)-induced senescence model using MIN6 mouse insulinoma β-cell line to elucidate the mechanisms by which senescence remodels organelle homeostasis and insulin secretion. Senescence was validated by senescence-associated β-galactosidase positivity, p16^(INK4a)/p21/p53 upregulation, and cell cycle arrest....

No abstract

Skin aging is a multifactorial process influenced by intrinsic and extrinsic factors, including cellular senescence, photoaging, glycation, and impaired wound healing, all of which begin at birth. Recent epigenetic research has identified non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), as key regulators of gene networks governing skin homeostasis, regeneration, and aging. However, the literature remains fragmented, lacking...

Population aging has become a global challenge, with its molecular mechanisms incompletely understood. The signal transducer and activator of transcription 3 (STAT3), a pleiotropic cytoplasmic transcription factor, is extensively involved in almost all hallmarks of aging, exhibiting paradoxical dual roles in senescence progression. This review summarizes the structure of STAT3 and its key posttranslational modifications (PTMs), including phosphorylation (Y705, S727), acetylation, and...

Lumbar multifidus (MF) muscle plays a key role in spinal stability, yet its adaptations to aging and disuse, which become increasingly prevalent with advancing age, remain unclear. We conducted two studies to investigate age- and inactivity-induced changes in MF size. In Study 1, we assessed 32 young adults (50% females) and 75 older adults (67% females), categorized as non-sarcopenic (NS) or probable sarcopenic (PS) based on EWGSOP2 criteria. In Study 2, we examined early MF responses to 10-day...

Interventional therapy and surgery play important roles in the treatment of various diseases, but they cause varying degrees of vascular injury. Currently, the side effects are often overlooked. Here, we observed abnormal nuclear morphology (nuclear dysmorphism) and vascular aging in injured human and rodent arteries. Platelet-derived microvesicles (PMVs) adhere to injured blood vessels, leading to nuclear dysmorphism and cell senescence in vascular smooth muscle cells (VSMCs). This occurs...

Previous studies from our lab identified functional defects in antigen-specific peripheral T follicular helper cells (pTfh), characterized by low IL-21 and high IL-2 production, contributing to non-responsiveness to the influenza vaccine in both aging and HIV. This study investigated how IL-21-induced STAT3 and IL-2-induced STAT5 activation in pTfh cells affects vaccine responses in aging people with HIV (PWH) and those without HIV (PWoH). Ninety participants, including young (Y, ≤ 40 years) and...

Pregnancy functions as a "stress test" with implications for women's long-term health. We hypothesize that maternal biological aging, measured by epigenetic age acceleration (EAA), can be influenced by one-carbon nutritional status (folate, vitamin B₁₂, homocysteine), adherence to the Mediterranean diet, and prenatal multivitamin use. We analyzed data from 742 mothers enrolled in the Boston Birth Cohort (1998-2013). EAA was defined as the difference between the Levine epigenetic clock-DNA...