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.
Highlights
Developed countries face an enormous increase in the elderly population
The integration of information on lipidomics with proteomics and expression profiles can help to shape the understanding of metabolic pathways as potential targets for future therapeutic interventions [20]
Comparing transcriptomic patterns of prematurely aged and long-lived mice, Schumacher et al detected genes involved in lipid metabolism among genes differentially expressed during the aging process in various tissues including the kidney [24]
Summary
Developed countries face an enormous increase in the elderly population. Estimates predict an increase in life expectancy to 88 years for men and to 91 years for women aged 65 in 2030 [1]. On the molecular level an increase of oxidative damage and its products as well as an increase in cyclin-dependent kinase (CDK) inhibitors such as p16, has been reported [2], leading to senescence especially in the cortical tubular system [4,5]. This contributes to a chronic inflammatory response with accumulating macrophages and lymphocytes in the interstitium [1,2,3,4]. The exact underlying molecular mechanisms for these changes remain largely unknown
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