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Updated: May 15, 2026
Quantitative Real-Time Polymerase Chain Reaction Evaluation of MicroRNA Expression in Kidney and Serum of Mice with Age-Dependent Renal Impairment
Published on: April 29, 2022
Age-associated molecular changes in the kidney in aged mice
Ji Hee Lim1, Eun Nim Kim, Min Young Kim
1Division of Nephrology, Department of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul 137-040, Republic of Korea.
Background:
Aging is a multifactorial process characterized by a progressive decline in physiological function. Decreased kidney function is associated with cardiovascular disease and mortality. Therefore, increasing our insight into kidney aging by understanding the anatomic, physiologic, and pathologic changes of aging in the kidney is important to prevent disastrous outcomes in elderly people.
Methods:
Male two-, 12-, and 24-month-old C57/BL6 mice were used in this study. We measured histological change, oxidative stress, and aging-related protein expression in the kidneys.
Results:
Twenty-four-month-old mice displayed increased albuminuria. Creatinine clearance decreased with aging, although this was not statistically significant. There were increases in mesangial volume and tubulointerstitial fibrosis in 24-month-old mice. There were also increases in F4/80 expression and in apoptosis detected by TUNEL assay. Urine isoprostane excretion increased with aging and SOD1 and SOD2 were decreased in 24-month-old mice. Oxidative stress may be mediated by a decrease in Sirt1, PGC-1α, ERR-1α, and PPARα expression. Klotho expression also decreased.
Conclusions:
Our results demonstrate that Sirt1 was decreased with aging and may relate to changed target molecules including PGC-1α/ERR-1α signaling and PPARα. Klotho can also induce oxidative stress. Pharmacologically targeting these signaling molecules may reduce the pathologic changes of aging in the kidney.
Insights
Kidney aging in mice shows increased albuminuria and fibrosis. Declines in Sirt1 and Klotho expression correlate with oxidative stress, suggesting potential therapeutic targets for age-related kidney decline.
Area of Science:
- Gerontology
- Nephrology
- Molecular Biology
Background:
- Aging is a complex process leading to physiological decline, with reduced kidney function linked to cardiovascular disease and mortality.
- Understanding kidney aging is crucial for preventing adverse outcomes in older populations.
Purpose of the Study:
- To investigate the anatomic, physiologic, and pathologic changes associated with kidney aging in a mouse model.
- To explore the role of oxidative stress and specific protein expression in kidney aging.
Main Methods:
- Utilized male C57/BL6 mice at 2, 12, and 24 months of age.
- Assessed kidney histology, oxidative stress markers (isoprostane), apoptosis (TUNEL assay), and expression of aging-related proteins (Sirt1, PGC-1α, Klotho, SOD1, SOD2, ERR-1α, PPARα).
Main Results:
- Older mice (24 months) exhibited increased albuminuria, mesangial volume, tubulointerstitial fibrosis, and apoptosis.
- Aging correlated with increased urine isoprostane excretion and decreased expression of SOD1, SOD2, Sirt1, PGC-1α, ERR-1α, PPARα, and Klotho.
- Creatinine clearance showed a non-significant decrease with age.
Conclusions:
- Aging kidneys show increased oxidative stress, potentially mediated by decreased Sirt1, PGC-1α/ERR-1α, and PPARα signaling.
- Reduced Klotho expression is associated with kidney aging and oxidative stress.
- Targeting these molecular pathways may offer therapeutic strategies to mitigate age-related kidney pathology.
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