Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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A novel micronutrient blend mimics calorie restriction transcriptomics in multiple tissues of mice and increases life and healthspan in C. Elegans

ABSTRACT: Calorie restriction is a major intervention consistently demonstrated to retard aging and delay age-associated diseases. A novel micronutrient blend, a putative calorie restriction mimetic, was developed based on a screening tool we previously described. Whole transcriptomic analysis was examined in brain cortex, skeletal muscle and heart in three groups of mice: old controls (30 months), old + calorie restriction and old + novel micronutrient blend. The micronutrient blend elicited transcriptomic changes in a manner similar to those in the calorie-restricted group and unique from those in the control group. Subgroup analysis revealed that nuclear hormone receptor, proteasome complex and angiotensinogen genes, all of which are known to be directly related to the aging process, were the most affected by the micronutrient blend and by calorie restriction. Thus, these three genes may be considered master regulators of the favorable effects of calorie restriction and of the micronutrient blend. Based on the calorie restriction mimetic effects on transcriptomics, it was hypothesized that the micronutrient blend would promotes longevity and vitality. To test this hypothesis, a functional analysis in C. Elegans was used to examine the effects of the micronutrient blend on longevity and biomarkers of vitality. Results indicate that feeding C. Elegans the micronutrient blend increased longevity as well as vitality. Further studies are required to confirm that the calorie restriction mimicking benefits described here are elicited by the micronutrient blend in humans.

ORGANISM(S): Mus musculus

SUBMITTER: Eva Serna

PROVIDER: E-MTAB-8506 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Cultivation methods used to investigate microbial calorie restriction often result in carbon and energy starvation. This study aims to dissect cellular responses to calorie restriction and starvation in Saccharomyces cerevisiae by using retentostat cultivation. In retentostats, cells are continuously supplied with a small, constant carbon and energy supply, sufficient for maintenance of cellular viability and integrity but insufficient for growth. When glucose-limited retentostats cultivated under extreme calorie restriction were subjected to glucose starvation, calorie-restricted and glucose-starved cells were found to share characteristics such as increased heat-shock tolerance and expression of quiescence-related genes. However, they also displayed strikingly different features. While calorie-restricted yeast cultures remained metabolically active and viable for prolonged periods of time, glucose starvation resulted in rapid consumption of reserve carbohydrates, population heterogeneity due to appearance of senescent cells and, ultimately, loss of viability. Moreover, during starvation, calculated rates of ATP synthesis from storage carbohydrates were 2-3 orders of magnitude lower than steady-state ATP-turnover rates calculated under extreme calorie restriction in retentostats. Stringent reduction of ATP turnover during glucose starvation was accompanied by a strong down-regulation of genes involved in protein synthesis. These results demonstrate that extreme calorie restriction and carbon starvation represent different physiological states in S. cerevisiae. The yeast was first grown for 14 days under extreme calorie restriction in anaerobic, glucose-limited retentostats (Boender et al., 2009, Appl.Environ.Microbiol., 75: 5607-5614.). Subsequently, starvation was started by terminating the glucose feed. Yeast transcriptional reprogramming in response to calorie restriction and starvation was monitored by microarray analysis. Independent duplicate retentostat cultures, and subsequently starvation, were sampled for transcriptome analysis using Affymetrix microarrays. One time-point was sampled during calorie restriction (T0) and four time points were sampled during the starvation phase 10, 30, 60 and 120 minutes after switching of the feed, resulting in a dataset of 10 arrays.

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A novel micronutrient blend mimics calorie restriction transcriptomics in multiple tissues of mice and increases life and healthspan in C. Elegans

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