A novel nutrient blend mimics calorie restriction transcriptomics in multiple tissues of mice and increases vitality and lifespan in C. elegans

Identification of caloric restriction mimetics (CRMs), compounds that mimic the beneficial effects of caloric restriction (CR) without limiting energy intake would be a scientific advancement. This study investigated transcriptomics elicited by a putative CRM nutrient blend compared to CR in diverse tissues following long-term feeding in 4 groups of B6C3F1 mice: Young Controls (YC; 5 months) and 3 groups treated from 14–30 months: Old Controls (OC), Old CR (OCR; 25% CR) and Old Supplemented (OS). Gene expression profiling in cerebral cortex (CC), skeletal muscle (SKL), heart (HRT), white adipose (WAT)and liver (LVR) was performed with Affymetrix Mouse 2.0ST arrays. This was followed by a dose-response study in C. elegans investigating longevity and mobility. Principal component analysis revealed that gene expression profiles of YC and OC were distinct from one another in all tissues except WAT at 30 months. The OS mimicked OCR transcriptomics most dramatically in tissues most relevant to aging and age-associated diseases, CCT, HRT and SKL. In C. elegans , the blend mimicked the known benefits of CR, increasing lifespan and vitality in a dose-dependent manner. These CRM effects may have positive implications for healthy human aging or ‘youthspan’ and warrant further investigation.