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Comparative Study
. 2012 Apr;34(2):329-39.
doi: 10.1007/s11357-011-9237-1. Epub 2011 Apr 1.

Age-related changes in the function of autophagy in rat kidneys

Jing Cui  1 , Xue-Yuan Bai, Suozhu Shi, Shaoyuan Cui, Quan Hong, Guangyan Cai, Xiangmei Chen
Affiliations
Comparative Study

Age-related changes in the function of autophagy in rat kidneys

Jing Cui et al. Age (Dordr). 2012 Apr.

Abstract

Autophagy is a highly regulated intracellular process for the degradation of cytoplasmic components, especially protein aggregates and damaged organelles. It is essential for maintaining healthy cells. Impaired or deficient autophagy is believed to cause or contribute to aging and age-related disease. In this study, we investigated the effects of age on autophagy in the kidneys of 3-, 12-, and 24-month-old Fischer 344 rats. The results revealed that autophagy-related gene (Atg)7 was significantly downregulated in kidneys of increasing age. The protein expression level of the autophagy marker light chain 3/Atg8 exhibited a marked decline in aged kidneys. The levels of p62/SQSTM1 and polyubiquitin aggregates, representing the function of autophagy and proteasomal degradation, increased in older kidneys. The level of 8-hydroxydeoxyguanosine, a marker of mitochondrial DNA oxidative damage, was also increased in older kidneys. Analysis by transmission electron microscope demonstrated swelling and disintegration of cristae in the mitochondria of aged kidneys. These results suggest that autophagic function decreases with age in the kidneys of Fischer 344 rats, and autophagy may mediate the process of kidney aging, leading to the accumulation of damaged mitochondria.

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Figures

Fig. 1
Fig. 1
Expression of senescent biomarker p16 in the kidneys of 3-, 12-, and 24-month-old Fischer 344 rats. a Western blot results for p16 protein. b Quantitative analysis of band density for p16. Protein expression data are presented as mean ± SD (n = 10). *p < 0.05 vs young; #p < 0.05 vs adult
Fig. 2
Fig. 2
Senescence-associated β-galactosidase staining results for renal tissues from 3-, 12-, and 24-month-old Fischer 344 rats. Magnification, ×400. Blue precipitation in the cytoplasm was observed in the senescent cells
Fig. 3
Fig. 3
Dual immunofluorescence staining results for LC3 proteins (red), 8-OHdG (green), and the colocalization (yellow) of LC3 and 8-OHdG in the kidneys of 3-, 12-, and 24-month-old Fischer 344 rats were scanned by a laser confocal microscope. Magnification, ×600. Central glomeruli are indicated by an arrow. Peripheral tubules are indicated by an arrowhead
Fig. 4
Fig. 4
a Expression of LC3-I and LC3-II proteins in the renal tissues of 3-, 12-, and 24-month-old Fischer 344 rats was quantified by Western blot analysis. b Ratio of LC3-II band and LC3-I band was analyzed. c, d Quantitative analysis of band density for LC3-I and LC3-II. Protein expression data are presented as mean ± SD (n = 10). *p < 0.05 vs young; #p < 0.05 vs adult
Fig. 5
Fig. 5
Expression of Atg7 (a) and Atg5 (b) mRNA in tissue extracts of kidneys of 3-, 12-, and 24-month-old Fischer 344 rats was measured by quantitative PCR. Data are presented as mean ± SD (n = 10). *p < 0.05 vs young
Fig. 6
Fig. 6
a, c Expression of p62/SQSTM1 and polyubiquitin aggregates in tissue extracts of kidneys of 3-, 12-, and 24-month-old Fischer 344 rats was quantified by Western blot. b Quantitative analysis of band density for p62/SQSTM1. Protein expression data are presented as mean ± SD (n = 10). *p < 0.05 vs young; #p < 0.05 vs adult
Fig. 7
Fig. 7
Detection of 8-OHdG level by immunohistochemistry staining
Fig. 8
Fig. 8
Analysis of mitochondrial structures by transmission electron microscopy in the renal tissues of 3-, 12-, and 24-month-old Fischer 344 rats. Arrowheads indicate regular mitochondria; arrows indicate damaged mitochondria. a Three-, b 12-, and c 24-month-old Fischer 344 rats
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