Lacayo, P. | bioRxiv Science

bioRxiv2025

Red-wine gene networks associated with exceptional longevity in humans

Moderate consumption of red wine has been associated with healthy aging and longevity, defined as one drink per day for women and two drinks per day for men (approximately 142 ml or 5 oz per drink). Previous research has revealed the health benefits of red wine, particularly in relation to cardiovascular disease. However, the influence of genetic factors on these benefits remains to be elucidated. In this study, we explored genes linked to red wine and created a curated gene set that intersects with those related to centenarians, who are markers of exceptional longevity. Utilizing over 190 databases, we identified and validated a curated list of genes, and conducted gene set enrichment analysis as well as enrichment analysis of annotations and diseases. Our findings highlighted 43 genes connected to centenarians, suggesting that these genes play a crucial role in stress response and apoptosis, which are essential for cell survival and renewal. Additionally, we noted that these genes were enriched in pathways associated with smooth muscle cell proliferation, neuroinflammation, nucleotide excision repair, and lipoprotein metabolism (false discovery rate, FDR < 3 x 10-07). Gene set enrichment analysis indicated significant tissue expression in the gastrointestinal, cardiovascular, and respiratory systems. Furthermore, the disease-gene enrichment analysis pointed to associations with the diseases related to the tissues, including cardiovascular disease (heart disease and stroke), type 2 diabetes, gastrointestinal diseases and metabolic diseases, immune diseases, and cancer (FDR < 9.37 x 10-6); notably, cardiovascular diseases, diabetes, and cancer are leading causes of death, suggesting that the genes may be protective against those diseases. Although further research is necessary to uncover additional genes, this study provides the first genetic overview of the health benefits of red wine, emphasizing its potential in supporting healthy aging and longevity.

genomics↗

bioRxiv2024

Biology of healthy aging: Biological hallmarks of stress resistance-related and unrelated to longevity in humans

Stress resistance is tightly associated with longer and healthier lifespans in various model organisms, including nematodes, fruit flies, and mice. However, we lack a complete understanding of stress resistance in humans, and therefore, we investigated how stress resistance and longevity are interlinked in humans. Using more than 180 databases, we identified 541 human genes associated with stress resistance. The curated gene set is highly enriched with genes involved in cellular response to stress. The Reactome analysis identified 398 biological pathways, narrowed down to 172 pathways, using a medium threshold (p-value < 1 x 10-04). We further summarized into 14 pathway categories, e.g., cellular response to stimuli/stress, DNA repair, gene expression, and immune system. There were overlapping categories between stress resistance and longevity, including gene expression, signal transduction, immune system, and cellular responses to stimuli/stress. The categories include the PIP3-AKT-FOXO and mTOR pathways, known to specify lifespans in the model systems. They also include the accelerated aging syndrome genes (WRN and HGPS/LMNA), while the genes were also involved in non-overlapped categories. Notably, nuclear pore proteins are enriched among the stress resistance pathways and overlap with diverse metabolic pathways. This study suggests that stress resistance is closely linked with longevity pathways, but not entirely identical. While most longevity categories intersect with stress-resistance categories, some do not, particularly those related to cell proliferation and beta-cell development. We also note inconsistencies in pathway terminologies with aging hallmarks reported previously and propose them to be more unified and integral.

genomics↗