Complement C3 deficiency ameliorates aging related changes in the kidney
Xiaoting Wu1, Liyu Lin1, Jiong Cui1
1Department of Nephrology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Aims:
Complement C3 (C3) has been shown to be involved in the aging process. However, the role of C3 in kidney aging has not been fully elucidated. This study aimed to investigate the effect of C3 on senescence related kidney disorders in mice.
Materials And Methods:
Two-, 8-, and 16-month-old C3-deficient male mice (KO) (n = 6) and age-, gender-, and strain- matched wild type (WT) C57BL/6 mice (n = 6) were selected to represent young, middle-aged and aging mice. Renal, blood and urine samples were collected. Hematoxylin-eosin (HE), Masson, and immunohistochemistry (IHC) staining as well as ELISA and Western blotting were used to explore the mechanisms involved in renal aging.
Key Findings:
The level of C3 was upregulated during aging in WT mice. The glomerular sclerosis index and tubulointerstitial fibrosis index were increased significantly in WT mice during aging. Renal function was not significantly different between the young and aged groups. Compared with those in WT mice, the levels of inflammation and fibrosis were decreased, while the expression of CD31 was significantly increased in the KO group.
Significance:
Our data demonstrated that age-related changes in renal structure occur earlier than functional changes and that complement C3 is involved in aging-related kidney disorder.
Insights
Complement C3 (C3) contributes to kidney aging and age-related kidney disorders in mice. Reducing C3 levels in mice lessened inflammation and fibrosis, suggesting a therapeutic target for aging kidneys.
Area of Science:
- Nephrology
- Immunology
- Aging Research
Background:
- Complement C3 (C3) is implicated in aging processes.
- The specific role of C3 in kidney aging remains unclear.
Purpose of the Study:
- To investigate the impact of C3 on age-related kidney disorders in a mouse model.
- To elucidate the mechanisms underlying C3's involvement in renal aging.
Main Methods:
- Comparison of C3-deficient (KO) and wild-type (WT) mice at young, middle-aged, and aging stages (2, 8, 16 months).
- Analysis of renal, blood, and urine samples using histological staining (HE, Masson), immunohistochemistry (IHC), ELISA, and Western blotting.
Main Results:
- C3 levels increased with age in WT mice, correlating with elevated glomerular and tubulointerstitial fibrosis.
- Renal function showed no significant age-dependent decline.
- KO mice exhibited reduced inflammation and fibrosis, and increased CD31 expression compared to WT mice.
Conclusions:
- Age-related structural kidney changes precede functional decline.
- Complement C3 plays a significant role in the development of aging-related kidney disorders.
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