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INTRODUCTION: Primitive reflexes (PRs) are brainstem-mediated automatic responses that typically disappear in early life, but may reappear in older age, which may be associated with neurodegenerative processes. But the presence of PRs in cognitively healthy adults has not yet been sufficiently explored. The relationship between PRs and cognitive functioning (COG) may be influenced by modifiable factors such as physical activity (PA) and psychological resilience. This cross-sectional...

Systematic price monitoring sheds light on economics of online manipulation

Parkinson's disease (PD) is a neurodegenerative disease that manifests motor and non-motor symptoms due to the progressive loss of dopaminergic neurons in the substantia nigra. While its pathogenesis is multifactorial, with genetic as well as environmental components, more and more evidence suggests that nutrition and diet play an important role in regulating both the development and progression of the disease through crosstalk with genetics, a term known as nutrigenomics. This review discusses...

Cellular senescence contributes to age-related neurodegeneration, yet its manifestation varies across brain cell types and senescence-inducing stressors. Here, we investigated senescence hallmarks in five human brain cell lines - astrocytes, endothelial cells, microglia, oligodendrocytes, and dopaminergic-like neurons - using chronic 5-Bromodeoxyuridine treatment and validated our findings in primary cells and alternative toxin-induced models. Principal component analysis and transcriptional...

Transcriptome- and proteome-wide association studies (TWAS/PWAS) have proven successful in prioritizing genes and proteins whose genetically regulated expression modulates disease risk, but they ignore potential co-expression and interaction effects. To address this limitation, we introduce the co-expression-wide association study (COWAS) method, which can identify pairs of genes or proteins whose genetically regulated co-expression is associated with complex traits. COWAS first trains models to...

CONCLUSIONS: In this nationally representative sample of Chinese older adults, social isolation is associated with greater decline of intrinsic capacity, partially mediated through inadequate sleep duration and pain complaints. These findings suggest that interventions aimed at mitigating social isolation, along with integrated management of sleep and pain, may help preserve intrinsic capacity in aging populations.

The TP53 tumor suppressor gene is mutated in a large fraction of human tumors. Close to 11% of TP53 mutations are nonsense mutations, causing premature termination of protein synthesis and expression of truncated inactive p53 protein. The most common TP53 nonsense mutation in human cancer is R213X. To study the impact of TP53 nonsense mutations in vivo, we generated mice harboring the Trp53 nonsense mutation R210X that corresponds to human TP53-R213X. Initially, Trp53^(R210X) mice appear...

Cellular senescence contributes to age-related neurodegeneration, yet its manifestation varies across brain cell types and senescence-inducing stressors. Here, we investigated senescence hallmarks in five human brain cell lines - astrocytes, endothelial cells, microglia, oligodendrocytes, and dopaminergic-like neurons - using chronic 5-Bromodeoxyuridine treatment and validated our findings in primary cells and alternative toxin-induced models. Principal component analysis and transcriptional...

Insulin/insulin-like growth factor signaling inhibits FOXO transcription factors to control development, homeostasis, and aging. Here, we use proximity labeling to identify proteins interacting with the C. elegans FOXO DAF-16. We show that in well-fed, unstressed animals harboring active insulin signaling, DAF-16 forms a complex with the PAR-1/MARK serine/threonine kinase, a key regulator of cell polarity. PAR-1 inhibits DAF-16 accumulation and promotes DAF-16 phosphorylation at S249, at a...

Aberrant innate immune responses contribute significantly to cellular senescence, yet the precise interplay between innate immunity and senescence remains poorly characterized. Here, we elucidate the pivotal role of nuclear respiratory factor 1 (NRF1) in orchestrating innate immune responses that drive senescence and the senescence-associated secretory phenotype (SASP). NRF1 deficiency delayed cellular senescence and ameliorated age-related deterioration in multiple organs. Mechanistically, NRF1...

Organ-specific plasma protein signatures identified via proteomics profiling could be used to quantitatively track organ aging. However, the genetic determinants and molecular mechanisms underlying the organ-specific aging process remain poorly characterized. Here we integrated large-scale plasma proteomic and genomic data from 51,936 UK Biobank participants to uncover the genetic architectures underlying aging across 13 organs. We identified 119 genetic loci associated with organ aging,...

Caloric restriction prolongs lifespan and preserves health across species, with feeding times synchronized to day-night cycles further maximizing benefits. However, the mechanisms linking diet, diurnal rhythms, and lifespan remain unclear. In mice, the time point most strongly tied to dietary effects on lifespan coincides with the peak of glucocorticoid secretion (ZT12, lights-off). Caloric restriction raises circulating glucocorticoid hormone levels, implicating these signals as candidate...

During aging and cellular senescence, repetitive elements are frequently transcriptionally derepressed across species and cell types. Among these, the most abundant repeats by copy number in the human genome are Alu retrotransposons. Though Alu elements are often studied for their mutagenic potential, there is increasing appreciation for their contributions to other biological functions, including pro-inflammatory signaling and mitochondrial dysfunction. However, a comprehensive analysis of...

The cognitively-intact oldest-old (85 +) may be the most-resilient members of their birth cohort; due to survivorship effects (e.g., depletion of susceptibles), risk factors associated with brain aging biomarkers in younger samples may not generalize to the cognitively-intact oldest-old. We evaluated associations between established aging-related risk factors and brain-predicted age difference (brainPAD) in a cross-sectional cognitively-intact oldest-old sample. Additionally, we evaluated...

Local brain age (LBA) is a regional metric of brain aging that offers a spatially resolved alternative to global brain age, but whose genetic basis is unexplored. This study reports the first genome-wide association study of cortical LBA, as estimated by a deep neural network from the T(1)-weighted magnetic resonance images of 41,708 cognitively normal adults in the UK Biobank. We identified 1,212 single-nucleotide polymorphisms (SNPs) significantly associated with LBA in at least one brain...

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Transcription is regulated in part through histone proteins. Histones can be replaced with variant forms that are particularly critical in the brain and accumulate throughout the lifespan. Recent findings demonstrated that the histone variant H2BE regulates chromatin structure, neuronal transcription, and mouse behavior. However, the role of H2BE in other cell types and throughout the lifespan remains unknown. Here, we discovered that H2BE is enriched in astrocytes and accumulates with age in...

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Calcium carbonate precipitation in ageing ocean crust sequesters carbon dioxide dissolved in seawater through seafloor weathering reactions, influencing atmospheric CO(2) concentrations on million-year timescales. However, this crustal carbon sink, and the extent it balances CO(2) degassing during crustal formation at mid-ocean ridges, remain poorly quantified due to limited sampling of the vast ridge flanks where CO(2) uptake continues for millions of years. Here we quantify the carbon sink...