Calorie Restriction Modulates Gene Expression of Il19 and Il24 during Renal Aging
Sang Gyun Noh1, Hyun Woo Kim1, Seungwoo Kim2
1Research Institute for Drug Development, Pusan National University, Busan, Korea.
Background:
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.
Methods:
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).
Results:
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 interleukin 20 (IL-20) family, particularly Il19 and Il24. Furthermore, experimental induction of cellular senescence using H2O2 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.
Conclusion:
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.
Insights
Aging kidneys show increased inflammation and senescence markers. Short-term calorie restriction (CR) reversed these changes, particularly affecting IL-20 family genes (Il19, Il24), suggesting potential therapeutic targets for age-related renal decline.
Area of Science:
- Gerontology and Nephrology
- Molecular Biology and Genetics
- Bioinformatics and Systems Biology
Background:
- Kidney function declines with age due to increased inflammation and cellular senescence.
- Cellular senescence is characterized by the senescence-associated secretory phenotype (SASP).
- Calorie restriction (CR) is a known intervention with anti-aging properties.
Purpose of the Study:
- To investigate gene expression changes associated with renal aging.
- To determine if short-term CR can reverse age-related gene expression alterations in the kidney.
- To explore the role of IL-20 family genes in renal aging and senescence.
Main Methods:
- RNA sequencing (RNA-seq) to identify differentially expressed genes.
- Bioinformatics and systems biology analyses for gene ontology and pathway analysis.
- Quantitative analysis of renal tissue and experimental induction of senescence.
Main Results:
- Aging kidneys exhibited altered expression of SASP genes (e.g., Il1b, Ccl3, Ccl5, Il19, Il24, Timp1, Mmp12).
- CR suppressed age-associated upregulation of cell cycle arrest markers (Cdkn2b, Cdkn2a, Cdkn1a).
- Il19 and Il24 expression increased with aging and senescence induction, and were modulated by CR.
Conclusions:
- Aging and CR impact the expression of IL-20 family genes, influencing cellular senescence.
- Il19 and Il24 are associated with age-related renal decline.
- These genes represent potential targets for future research into kidney aging and therapeutic interventions.
