Altered lipid metabolism in the aging kidney identified by three layered omic analysis
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Altered lipid metabolism in the aging kidney identified by three layered omic analysis. / Braun, Fabian; Rinschen, Markus M; Bartels, Valerie; Frommolt, Peter; Habermann, Bianca; Hoeijmakers, Jan H J; Schumacher, Björn; Dollé, Martijn E T; Müller, Roman-Ulrich; Benzing, Thomas; Schermer, Bernhard; Kurschat, Christine E.
In: AGING-US, Vol. 8, No. 3, 03.2016, p. 441-57.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Altered lipid metabolism in the aging kidney identified by three layered omic analysis
AU - Braun, Fabian
AU - Rinschen, Markus M
AU - Bartels, Valerie
AU - Frommolt, Peter
AU - Habermann, Bianca
AU - Hoeijmakers, Jan H J
AU - Schumacher, Björn
AU - Dollé, Martijn E T
AU - Müller, Roman-Ulrich
AU - Benzing, Thomas
AU - Schermer, Bernhard
AU - Kurschat, Christine E
PY - 2016/3
Y1 - 2016/3
N2 - 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.
AB - 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.
KW - Acid Ceramidase
KW - Aging
KW - Animals
KW - Ceramides
KW - Kidney
KW - Lipid Metabolism
KW - Mass Spectrometry
KW - Mice, Inbred C57BL
KW - Phenotype
KW - Phospholipids
KW - Proteomics
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, Non-U.S. Gov't
U2 - 10.18632/aging.100900
DO - 10.18632/aging.100900
M3 - SCORING: Journal article
C2 - 26886165
VL - 8
SP - 441
EP - 457
JO - AGING-US
JF - AGING-US
SN - 1945-4589
IS - 3
ER -