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Increasing evidence suggests that red and processed meat consumption may elevate the risk of colorectal cancer (CRC), yet the magnitude and consistency of this association remain debated. This meta-analysis aims to quantify the relationship between red and processed meat intake and the risk of CRC, colon cancer, and rectal cancer using the most comprehensive set of prospective studies to date. We conducted a comprehensive search in PubMed, Web of Science, Cochrane Library, Embase, and Google...

Aging and COVID- 19 are known to influence DNA methylation, potentially affecting the rate of aging and the risk of disease. The physiological functions of 54 volunteers-including maximal oxygen uptake (VO₂ max), grip strength, and vertical jump-were assessed just before the COVID- 19 pandemic and again 3 years later. Of these volunteers, 27 had contracted COVID- 19. Eight epigenetic clocks were used to assess the rate of aging during the 3-year period: DNAmAge showed accelerated aging, and five...

The clinical and pathological outcomes differ between early-onset (diagnosed in men ≤55 years of age) and late-onset prostate cancer, potentially attributed to the changes in hormone levels and immune activities associated with aging. Exploring the heterogeneity therein holds potential for developing age-specific precision interventions. Here, through single-cell and spatial transcriptomic analyses of prostate cancer tissues, we identified that an androgen response-related transcriptional...

Three-dimensional (3D) genome organization becomes altered during development, aging and disease, but the factors regulating chromatin topology are incompletely understood and currently no technology can efficiently screen for new regulators of multi-scale chromatin organization. Here, we developed an image-based high-content screening platform (Perturb-tracing) that combines pooled CRISPR screens, a cellular barcode readout method (BARC-FISH) and chromatin tracing. We performed a...

Variants in GBA1 resulting in decreased lysosomal glucocerebrosidase (GCase) activity are a common risk factor for Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Incomplete penetrance of GBA1 variants suggests that additional genes contribute to PD and DLB manifestation. By using a pooled genome-wide CRISPR interference screen, we identified copper metabolism MURR1 domain-containing 3 (COMMD3) protein, a component of the COMMD/coiled-coil domain-containing protein 22...

The Atg8-family proteins, including LC3B (microtubule-associated protein 1 light chain 3 beta), are pivotal for key steps in the autophagy process. Proper regulation of LC3B homeostasis is essential for its function. Although LC3B is modulated by various posttranslational modifications (PTMs), the impact of these modifications on LC3B protein homeostasis remains unclear. Neddylation, a recently identified ubiquitin-like modification, plays diverse biological roles. Here, we identify LC3B as a...

Genetic effects on complex traits may depend on context, such as age, sex, environmental exposures, or social settings. However, it remains often unclear if the extent of context dependency, or gene-by-environment interaction (GxE), merits more involved models than the additive model typically used to analyze data from genome-wide association studies (GWAS). Here, we suggest considering the utility of GxE models in GWAS as a trade-off between bias and variance parameters. In particular, we...

The present paper provides the first integrated assessment of the capacity of the flavonol, fisetin, to induce hormetic dose responses. Fisetin was shown to induce hormetic dose responses in cellular and in vivo animal model systems affecting a broad range of endpoints of potential therapeutic and public health significance across the entire lifespan. Fisetin was effective in slowing aging processes, acting as a senolytic agent in multiple organ systems, in an hormetic fashion. In addition,...

Spermidine is a naturally occurring polyamine present in all cells and is necessary for viability in eukaryotic cells. The cellular levels of spermidine decline as an organism ages, and its supplementation has been found to extend lifespan in yeast, worms, flies, mice, and human cultured cells. The lifespan extending effect of spermidine is thought to be due to its ability to induce autophagy, a turnover of cellular components. Mitochondrial dysfunction is believed to be a major driver of the...

Chaperone-mediated autophagy (CMA) is a selective autophagic pathway that targets specific proteins for lysosomal degradation, playing a crucial role in maintaining cellular homeostasis. Recent research has highlighted the involvement of CMA in aging and age-related diseases, yet its regulation remains complex. The study by Khawaja et al. provides novel insights into the sex-specific and cell-type-specific regulation of CMA during aging. This commentary discusses the key findings of this study,...

ObjectiveWe compared pain prevalence and intensity between caregivers and non-caregivers, as well as between different types of caregivers.MethodUsing two rounds of data from the National Social Life, Health, and Aging Project, we used regression models to analyze differences in pain prevalence and intensity between caregivers and non-caregivers at baseline (2010-2011) and follow-up (2015-2016). The sample consisted of 2332 participants aged 62 and older (352 caregivers and 1980...