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Shared Mechanisms in Adenylyl Cyclase Type 5 Knockout and Caloric Restriction
Author(s) -
Yan Lin,
Park Ji Yeon,
De Lorenzo Mariana S.,
Ge Hui,
Lai Lo,
Tian Bin,
Sadoshima Junichi,
Vatner Dorothy E.,
Vatner Stephen F.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.528.9
Adenylyl cyclase type 5 knocked out mice (AC5KO) exhibit a ~30% increase in lifespan compared with wild‐type (WT) littermates, similar to caloric restriction (CR). AC5 KO eat more, but actually weigh less and accumulate less fat compared to WT mice. These data suggest that despite restricted food intake in CR, but augmented food intake in AC5 KO, the two models affect longevity and metabolism similarly. To identify shared mechanisms between CR WT and normal diet AC5 KO, RNA samples of liver, heart, skeletal muscle and brain were subjected to microarray analysis. Significantly regulated genes (greater than 1x standard deviation of all genes) were selected. Despite that some genes are regulated in a model‐specific manner, significantly more genes are commonly regulated than oppositely regulated in the two models (P < 0.01 for all 4 tissues): 3.4 fold difference in liver, 4.3 fold in brain, 15 fold in heart, and 19 fold in skeletal muscle. This result was further supported by Gene Ontology (GO) analysis, which identified many significantly regulated, tissue‐specific pathways shared by the two models, e.g. lipid metabolism in liver, sensory perception in heart and brain, and muscle function in skeletal muscle. These similarly regulated genes and pathways in AC5 KO and CR could lead to a unified theory for longevity.