Aging & Longevity

Aging is associated with profound alterations in gut microbiota composition and function, including reduced production of short-chain fatty acids (SCFAs), yet it remains unclear whether these age-related microbial changes directly contribute to impaired antiviral defense during influenza A virus (IAV) infection. To address this question, we first characterized age-associated alterations of the gut microbiome and SCFA-related metabolic potential in a murine model of IAV infection. We then used a...

Aging is the predominant risk factor for cardiac dysfunction, driven primarily through a decline in cardiomyocyte and overall myocardial performance. Cellular senescence is becoming increasingly linked to its development, as senescent cardiomyocytes and interstitial cells accumulate with age and exhibit persistent DNA damage, mitochondrial dysfunction, and inflammation that collectively impair ventricular relaxation and contractility. Senolytics, which selectively eliminate senescent cells,...

Age-associated loss of skeletal muscle mass and function, also known as sarcopenia, is closely linked to mitochondrial dysfunction. In this study, we report that senescent skeletal muscle myoblasts exhibit elevated activity and expression of the enzyme glutaminase (GLS1), which is mediated by p38 MAPK signaling and leads to intracellular urea accumulation that impairs mitochondrial function. Pharmacological inhibition of GLS1 with CB-839 reduced urea levels, restored the expression of electron...

Community context is an important determinant of health for older and aging adults. However, much of the research examining these associations has focused on Western contexts. Features and attributes of communities in low- and middle-income countries that might also shape health outcomes among older adults are less understood. This cross-sectional study examines community-level toilet coverage in India as a possible determinant of depression among adults over 45. We applied a multilevel modeling...

Dietary patterns are modifiable determinants of dementia risk, but the interactions between individual dietary preference profiles, biological aging, and dementia risk remain unclear. We aimed to investigate associations of dietary preference profiles with biological aging and incident dementia, as well as the potential modifying effect of genetic susceptibility. Dietary preference profiles were identified using latent profile analysis on food preferences questionnaire data. Cox models estimated...

AgingHallmarksDB is an interactive web platform designed to facilitate systems-level aging research centered on 11 aging hallmarks. It comprises 3111 aging hallmark-associated genes integrated from seven established databases, including a high-confidence consensus set comprising 1089 genes. It further incorporates tissue, cell-type class, exosomes, protein-protein and regulatory interactions to facilitate deeper biological insights. AgingHallmarksDB enables over representation analysis (ORA) and...

CONCLUSION: Our findings underscore the relevance of wealth as an important socioeconomic resource for cognitive health beyond income and education, particularly in old age, when income is typically reduced. Overall, the results support modest concurrent associations between personality, SES, and episodic memory levels, but provide hardly any evidence for longitudinal effects. More frequent and longer-term longitudinal assessments are needed to clarify potential effects on cognitive aging.

Aldabra giant tortoises (Aldabrachelys gigantea) are exceptionally long-lived. We sequenced the genome and methylome of Jonathan, a 194-year-old Aldabra, to explore the molecular basis of his longevity. Relative to other giant tortoises (A. gigantea and Chelonoidis abingdonii), Jonathan has unique gene variants in most aging pathways. Moreover, Jonathan has substantial DNA methylation and methylation entropy changes compared to four other Aldabras ranging in age from a 5-year-old juvenile to...

The cis-regulatory potential of human endogenous retroviruses (HERVs) that have accumulated in our genome affects diverse host processes, including embryonic development and malignancy, where HERV epigenetic control is reduced. Non-small cell lung cancer optimal growth requires cancer cell-intrinsic expression of the calcium-binding protein calbindin under the control of a HERVH integrant on chromosome 8q21.3. Chimeric transcription of HERVH and CALB1, encoding calbindin, is also observed in...

In vitro models of vascular disease have focused primarily on the pathophysiology of smooth muscle cell (SMC) or endothelial cell (EC). Adventitial fibroblasts can contribute to disease progression, but their specific influence is not well understood in different disease contexts. To elucidate fibroblast's impact on vascular pathology, we developed trilayer tissue-engineered blood vessels (TEBVs) with SMCs, ECs, and fibroblasts. We modeled atherosclerosis in the accelerated aging disease,...

CONCLUSION: In this cross-sectional analysis, higher AIP, reflecting atherogenic dyslipidemia, was associated with a modestly higher DBS-derived p-tau217 concentration in older adults. The biological and clinical significance of this association remains to be established in longitudinal and multimodal studies.

Prior work in older adults has developed a brief functional fine motor test, which involves repeated timed trials of an upper-limb task. Performance has been associated with global and domain-specific neuropsychological tests as well as putative markers of Alzheimer's disease when scored using variability in trial time; however, the extent to which task performance depends on motor ability has not been established nor quantified. This retrospective study examined whether mean trial time and...

Alzheimer's disease (AD) pathology is amplified by a self-reinforcing metal-Aβ-ROS axis, in which redox-active Cu and Fe bound to Aβ N-terminal histidines catalyze Fenton-like ROS generation and accelerate aggregation. Existing single-target interventions - anti-amyloid antibodies, antioxidants, metal-protein attenuating compounds, aggregation inhibitors, and photooxygenation catalysts - each address only one node of this loop. We used a computational-first framework to evaluate a dual-function...

Age-related impairment of brain solute clearance has been implicated in Alzheimer's disease (AD), yet procedures described as deep cervical lymphovenous reconstruction do not necessarily target the same lymphatic structure. This review examines glymphatic exchange, meningeal lymphatic drainage, cervical outflow, human lymphatic imaging, lymphatic surgery, early clinical studies, registered trials, and reported harms. Three interfaces can be distinguished: lymphatic flap-vein, lymph node-vein,...

Understanding how genetic influences on complex traits change with age is a fundamental question in genetic epidemiology. Both cross-sectional (between-subject) and longitudinal (within-subject) approaches can contribute to answering this question but come with distinct strengths and limitations. Here we show that age-varying genetic effects obtained from the two designs were highly concordant in direction (84.21% of the 57 identified variants) but showed only moderate agreement in effect-size...

Aging drives molecular changes that impair cellular and tissue function. Lipids are central to membrane structure, signaling and energy storage, yet their remodeling during aging remains unclear. Here, using cross-species, multi-tissue lipidomics, we identify elongation of lipid acyl chains as a conserved hallmark of aging across mice, Caenorhabditis elegans, Drosophila and humans. Similar lengthening occurs during the progression of human heart disease, whereas dietary restriction shortens...

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Higher-order chromatin structure is linked to cell differentiation and aging, but its native distribution in tissues and role in organismal development remain unclear. Here, we introduce SpaceA, a spatial omics approach for in situ chromatin architecture profiling. Compared with high-throughput chromosome conformation Capture (Hi-C), SpaceA captures substantially more contacts over distances beyond 10 Mb, thereby enhancing detection of higher-order chromatin dynamics. Applied to nine mouse...