Common mechanisms for calorie restriction and adenylyl cyclase type 5 knockout models of longevity

Adenylyl cyclase type 5 knockout mice (AC5 KO) live longer and are stress resistant, similar to calorie restriction (CR). AC5 KO mice eat more, but actually weigh less and accumulate less fat compared with WT mice. CR applied to AC5 KO results in rapid decrease in body weight, metabolic deterioration, and death. 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 determine shared molecular mechanisms, mRNA expression was examined genome-wide for brain, heart, skeletal muscle, and liver. Significantly more genes were regulated commonly rather than oppositely in all the tissues in both models, indicating commonality between AC5 KO and CR. Gene ontology analysis identified many significantly regulated, tissue-specific pathways shared by the two models, including sensory perception in heart and brain, muscle function in skeletal muscle, and lipid metabolism in liver. Moreover, when comparing gene expression changes in the heart under stress, the glutathione regulatory pathway was consistently upregulated in the longevity models but downregulated with stress. In addition, AC5 and CR shared changes in genes and proteins involved in the regulation of longevity and stress resistance, including Sirt1, ApoD, and olfactory receptors in both young- and intermediate-age mice. Thus, the similarly regulated genes and pathways in AC5 KO and CR mice, particularly related to the metabolic phenotype, suggest a unified theory for longevity and stress resistance.

Yan, Lin
Park, Ji Yeon
Dillinger, Jean-Guillaume
De Lorenzo, Mariana S.
Yuan, Chujun
Lai, Lo
Wang, Chunbo
Ho, David
Tian, Bin
Stanley, William C.
Auwerx, Johan
Vatner, Dorothy E.
Vatner, Stephen F.
Item Type: 
Journal Article
Publication Title: 
Aging Cell
Journal Abbreviation: 
Aging Cell
Publication Date: 
Publication Year: 
Library Catalog: 
NCBI Published Medical (?)
PMID: 23020244 PMCID: PMC3646327

Turabian/Chicago Citation

Lin Yan, Ji Yeon Park, Jean-Guillaume Dillinger, Mariana S. De Lorenzo, Chujun Yuan, Lo Lai, Chunbo Wang, David Ho, Bin Tian, William C. Stanley, Johan Auwerx, Dorothy E. Vatner and Stephen F. Vatner. 2012-12. "Common mechanisms for calorie restriction and adenylyl cyclase type 5 knockout models of longevity." Aging Cell 11: 6: 1110-1120. 10.1111/acel.12013.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1111/acel.12013 | issn = 1474-9726 | volume = 11 | pages = 1110-1120 | last = Yan | first = Lin | coauthors = Park, Ji Yeon, Dillinger, Jean-Guillaume, De Lorenzo, Mariana S., Yuan, Chujun, Lai, Lo, Wang, Chunbo, Ho, David, Tian, Bin, Stanley, William C., Auwerx, Johan, Vatner, Dorothy E., Vatner, Stephen F. | title = Common mechanisms for calorie restriction and adenylyl cyclase type 5 knockout models of longevity | journal = Aging Cell | date = 2012-12 | pmid = | pmc = }} </ref>