Calorie Restriction Modulates Gene Expression of Il19 and Il24 of during Renal Aging

Renal function declines with age as the kidneys become more vulnerable to inflammation and cellular senescence. This study examined gene expression changes linked to renal aging and assessed whether short-term calorie restriction (CR), a known anti-aging intervention, could reverse these alterations. Using RNA-seq data, we applied bioinformatics, systems biology, and molecular biology approaches to identify differentially expressed genes during aging and under CR. Gene Ontology and pathway analyses revealed that both aging and CR altered the expression of key senescence-associated secretory phenotype (SASP) genes, including cytokines and chemokines (Il1b, Ccl3, Ccl5, Il19, and Il24) and growth factors (Timp1 and Mmp12). Renal aging is also associated with an increased expression of cell cycle arrest markers (P15INK4B (Cdkn2b), P16INK4A (Cdkn2a), and P21 (Cdkn1a)), which are suppressed by CR, suggesting a link to cellular senescence. Quantitative analysis of renal tissue samples confirmed the age-associated upregulation of these genes at the transcriptional level, and CR effectively attenuated these changes. Among these genes, we focused on the members of the IL-20 family, particularly Il19 and Il24. Furthermore, experimental induction of cellular senescence using H₂O resulted in elevated Il19 and Il24 expression alongside other senescence markers. These findings suggest that aging and short-term CR regulate the IL-20 family expression, potentially influencing cellular senescence. Our study suggests that Il19 and Il24 are associated with age-related renal decline and may represent hypothesis-generating candidates, highlighting potential molecular targets for future mechanistic and therapeutic investigations.