Better Characterizing Calorie Restriction to Better Evaluate Calorie Restriction Mimetics

In this study, we utilized a gene expression profiling approach to identify robust tissue-specific transcriptional markers of CR that were significantly altered in expression in the majority of mouse strains tested. We focused on heart, gastrocnemius, white adipose tissue (WAT), and brain neocortex. Using quantitative PCR, we then screened seven candidate CRMs for their ability to influence the expression of some of the novel CR transcriptional markers in vivo. We also measured the effects of the candidate CRMs on previously characterized, nontranscriptional CR biomarkers. Importantly, we have shown that a drug that has strong activity in modulating CR transcriptional markers (pioglitazone) also modulates physiological measures of CR, such as reduced adipocyte size and mitochondrial mass. However, pioglitazone increased the levels of the inflammatory marker TNF-α, a finding suggestive of drug side effects. The putative CR mimetic L-carnitine, an amino acid involved in lipid metabolism, exhibited even stronger effects on CR transcriptional markers while modulating adipocyte size in a manner consistent with CR mimicry. These findings support the use of tissue-specific, robust transcriptional markers of CR as an effective approach to screen and identify compounds that have the potential to mimic the beneficial effects of CR on lifespan and healthspan. We also note that based on the finding that different compounds display tissue-specific CRM activity, it appears likely t...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs