- Calorie restriction reprograms single-cell transcriptional landscape of aging in mouse kidneys
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Su Woong Jung,Sang-Ho Lee,Jihwan Park
2022 ; 2022(1):
- 논문분류 :
- 춘계학술대회 초록집
Objectives: Kidney undergoes structural and functional deterioration with age whose progression may slow down by calorie restriction. However, cellular profiles of renal aging and its modulation by calorie restriction have not been investigated in detail.
Methods: Using single-cell RNA sequencing, we constructed a total of 75,750 single-cell atlas integrated the following C57BL/6 mouse kidneys after isolation of glomerular cells: young ad libitum (Y-AL) aged 8 weeks, old ad libitum (O-AL) aged 21 months, and old calorie restriction (O-CR) aged 21 moths whose dietary intake was reduced by half starting at 15-month-old. We explored the effect of aging and calorie restriction by comparing Y-AL vs. O-AL and O-CR vs. O-AL, respectively.
Results: All major cell types of the kidney were identified in the final dataset. On the basis of gene expression patterns, molecular characteristics of aging in podocytes, mesangial cells, and proximal tubular cells were characterized by upregulation in inflammation and downregulation in nephron development, which were partially restored by calorie restriction. In the context of metabolism and autophagy, aged podocyte had decreases in oxidative phosphorylation, citric acid cycle, N-glycan biosynthesis and autophagy, the last two of which were significantly recovered by calorie restriction. In addition, aged proximal tubular cells had increased gluconeogenesis, fatty acid degradation, and autophagy, the first two of which was further increased by calorie restriction in aged kidneys, representing boosting effects of dietary intervention on key metabolic activities in proximal tubular cells. Consistent with these alterations, gene regulatory networks underlying aging reverted by calorie restriction, such as Mafb downregulation by aging and upregulation of Mafb, Foxc1, and Nr3c1 by calorie restriction in podocytes.
Conclusions: Our data provides single-cell transcriptional landscapes driven by aging and calorie restriction in kidneys and new line of evidence supporting geroprotective effect of calorie restriction.