Open AccessIdentification of tissue‐specific transcriptional markers of caloric restriction in the mouse and their use to evaluate caloric restriction mimetics
Author(s) -
Barger Jamie L.,
Vann James M.,
Cray Nicole L.,
Pugh Thomas D.,
Mastaloudis Angela,
Hester Shelly N.,
Wood Steven M.,
Newton Michael A.,
Weindruch Richard,
Prolla Tomas A.
Publication year - 2017
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12608
Subject(s) - biology , carnitine , lipid metabolism , adipocyte , adipose tissue , endocrinology
Summary Caloric restriction ( CR ) without malnutrition has been shown to retard several aspects of the aging process and to extend lifespan in different species. There is strong interest in the identification of CR mimetics ( CRM s), compounds that mimic the beneficial effects of CR on lifespan and healthspan without restriction of energy intake. Identification of CRM s in mammals is currently inefficient due to the lack of screening tools. We have performed whole‐genome transcriptional profiling of CR in seven mouse strains (C3H/HeJ, CBA /J, DBA /2J, B6C3F1/J, 129S1/SvImJ, C57 BL /6J, and BALB / cJ ) in white adipose tissue ( WAT ), gastrocnemius muscle, heart, and brain neocortex. This analysis has identified tissue‐specific panels of genes that change in expression in multiple mouse strains with CR . We validated a subset of genes with qPCR and used these to evaluate the potential CRM s bezafibrate, pioglitazone, metformin, resveratrol, quercetin, 2,4‐dinitrophenol, and L‐carnitine when fed to C57 BL /6J 2‐month‐old mice for 3 months. Compounds were also evaluated for their ability to modulate previously characterized biomarkers of CR , including mitochondrial enzymes citrate synthase and SIRT 3, plasma inflammatory cytokines TNF ‐α and IFN ‐γ, glycated hemoglobin (HbA1c) levels and adipocyte size. Pioglitazone, a PPAR ‐γ agonist, and L‐carnitine, an amino acid involved in lipid metabolism, displayed the strongest effects on both the novel transcriptional markers of CR and the additional CR biomarkers tested. Our findings provide panels of tissue‐specific transcriptional markers of CR that can be used to identify novel CRM s, and also represent the first comparative molecular analysis of several potential CRM s in multiple tissues in mammals.