Collagen Gene Expression and Aging in Nematode Worms
Collagen molecules of various sorts are a vital component of the extracellular matrix, a complex supporting structure in tissues that is maintained by the cells that reside within it. Aging produces changes in this maintenance, in addition to a growing burden of alterations and damage to the molecules making up the extracellular matrix. Extracellular matrix aging is not as well studied as the aging of cells; this research exists at the intersection of the two, assessing age-related changes in the production of collagens needed for extracellular matrix maintenance in a short-lived laboratory species.
Collagens, long regarded as structural molecules, also regulate stress responses and longevity. In this study, we analyzed our RNA sequencing data and publicly available gene expression data to define their role in Caenorhabditis elegans aging. Collagen expression broadly declined with age, with 16 collagen genes consistently downregulated across independent studies, establishing collagen downregulation as a genetic hallmark of aging. In contrast, meta-analysis of 66 datasets (128 comparisons between normal and long-lived animals) showed collagen upregulation in 84% of long-lived conditions, identifying collagen induction as a conserved signature of lifespan extension.
Using collagen gene expression data, we applied K-means clustering and identified clusters that captured functional, tissue-associated subsets of collagens. Notably, aging-associated collagens were strongly enriched in Cluster 1, which overlapped with hypodermal collagens, while Cluster 2 significantly intersects with lifespan-extension and intestine-enriched subsets, and Cluster 3 likely represents structural collagens contributing to cuticle and muscle integrity. These results indicate that collagen genes grouped by expression-based clustering are not randomly distributed but instead reflect tissue-specific patterns and functionality.Together, our findings suggest that collagens are dynamic regulators of aging and longevity in C. elegans. Given the conservation of extracellular matrix biology across species, collagens represent candidate biomarkers and targets for promoting healthy aging in both C. elegans and higher animals.