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Altered lipid metabolism in the aging kidney identified by three layered omic analysis
Fabian Braun1,2, Markus M Rinschen1,2, Valerie Bartels1,3
1Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
Abstract:
Aging-associated diseases and their comorbidities affect the life of a constantly growing proportion of the population in developed countries. At the center of these comorbidities are changes of kidney structure and function as age-related chronic kidney disease predisposes to the development of cardiovascular diseases such as stroke, myocardial infarction or heart failure. To detect molecular mechanisms involved in kidney aging, we analyzed gene expression profiles of kidneys from adult and aged wild-type mice by transcriptomic, proteomic and targeted lipidomic methodologies. Interestingly, transcriptome and proteome analyses revealed differential expression of genes primarily involved in lipid metabolism and immune response. Additional lipidomic analyses uncovered significant age-related differences in the total amount of phosphatidylethanolamines, phosphatidylcholines and sphingomyelins as well as in subspecies of phosphatidylserines and ceramides with age. By integration of these datasets we identified Aldh1a1, a key enzyme in vitamin A metabolism specifically expressed in the medullary ascending limb, as one of the most prominent upregulated proteins in old kidneys. Moreover, ceramidase Asah1 was highly expressed in aged kidneys, consistent with a decrease in ceramide C16. In summary, our data suggest that changes in lipid metabolism are involved in the process of kidney aging and in the development of chronic kidney disease.
Insights
Changes in lipid metabolism are central to kidney aging and chronic kidney disease development. This study identified key enzymes and lipid alterations in aged mouse kidneys, revealing molecular mechanisms underlying age-related kidney dysfunction.
Area of Science:
- Gerontology
- Nephrology
- Biochemistry
Background:
- Aging-associated diseases and comorbidities, particularly chronic kidney disease (CKD), are increasing in developed countries.
- CKD is a major risk factor for cardiovascular diseases, including stroke, myocardial infarction, and heart failure.
- Understanding the molecular mechanisms of kidney aging is crucial for developing effective interventions.
Purpose of the Study:
- To investigate the molecular mechanisms involved in kidney aging.
- To identify age-related changes in gene expression, protein levels, and lipid profiles in mouse kidneys.
- To explore the role of lipid metabolism in kidney aging and CKD pathogenesis.
Main Methods:
- Transcriptomic, proteomic, and targeted lipidomic analyses were performed on kidneys from adult and aged wild-type mice.
- Differential gene expression and protein abundance were analyzed.
- Specific lipid subspecies, including phosphatidylethanolamines, phosphatidylcholines, sphingomyelins, phosphatidylserines, and ceramides, were quantified.
Main Results:
- Transcriptome and proteome analyses revealed significant alterations in genes and proteins related to lipid metabolism and immune response.
- Lipidomic analyses showed age-related differences in various lipid classes, notably phosphatidylethanolamines, phosphatidylcholines, sphingomyelins, phosphatidylserines, and ceramides.
- Aldh1a1 (a vitamin A metabolism enzyme) and Asah1 (a ceramidase) were identified as upregulated proteins in aged kidneys, correlating with changes in specific ceramide subspecies.
Conclusions:
- Changes in lipid metabolism are significantly involved in the process of kidney aging.
- Age-related alterations in lipid profiles and key metabolic enzymes contribute to kidney dysfunction and the development of chronic kidney disease.
- This study provides molecular insights into the interplay between aging, lipid metabolism, and kidney health.
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