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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,...

Scientists at UC San Francisco have developed a way to create cancer-fighting CAR-T cells directly inside the body, potentially avoiding the slow and extremely expensive process of removing, engineering, and reinfusing a patient’s immune cells. Using a two-particle delivery system, the researchers sent CRISPR gene-editing tools and new cancer-targeting DNA specifically into T cells, where the DNA was inserted at a precise location in the genome.