Abstract

A long-term vegetarian diet plays a role in the longevity and maintenance of the healthspan, but the underlying mechanisms for these observations are largely unknown. Particularly, it is not known whether a long-term vegetarian dietary pattern may affect the circulating miRNA expression in such a way as to modulate the healthspan. The Adventist Health Study-2 (AHS-2) cohort includes a large number of older adults who primarily follow vegetarian dietary patterns and reside in Loma Linda, California, one of five “Blue Zones” in the world in which a higher proportion of the population enjoys a longer than average lifespan. We performed miRNA-seq in 96 subjects selected from the AHS-2 cohort with different dietary patterns. We identified several differentially expressed miRNAs between vegetarians and non-vegetarians, which are involved in immune response and cytokine signaling, cell growth and proliferation as well as age-related diseases such as cardiovascular diseases and neurodegenerative diseases. Overall, our study showed that a vegetarian diet modulates aging-associated circulating miRNAs in a sex-dependent manner of differential expression for certain miRNAs, which may be related in a beneficial manner to the healthspan. Further investigation is needed to validate these miRNAs as potential biomarkers for diet-modulated longevity in humans.

Highlights

  • Aging is a complicated process that may be regulated by a combination of genetic factors, external environmental factors, and lifestyle factors such as diet and exercise, which modify epigenetic patterns including DNA methylation and chromatin remodeling.[1]

  • Our study showed that a vegetarian diet modulates aging-associated circulating miRNAs in a sex-dependent manner of differential expression for certain miRNAs, which may be related in a beneficial manner to the healthspan

  • In searching for potential biomarkers to monitor the effect of vegetarian diets on human healthspan and longevity and to investigate healthspan and lifestyle associations at a molecular level, we aimed to identify a range of circulating miRNAs that are differentially expressed among Adventist Health Study-2 (AHS-2) participants with different dietary patterns using deep miRNA sequencing

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Summary

Introduction

Aging is a complicated process that may be regulated by a combination of genetic factors, external environmental factors, and lifestyle factors such as diet and exercise, which modify epigenetic patterns including DNA methylation and chromatin remodeling.[1] With dietary and caloric restriction shown to be effective interventions to increase lifespan in animal models and humans, interest in the relationships between diet and aging has grown.[2,3] the molecular mechanisms underlying how diet affects lifespan and healthspan (commonly defined by the period of life spent in good health, free from chronic diseases and disabilities associated with aging) are not thoroughly understood, nutrient-sensing pathways are thought to play an important role.[4,5] Nutrientsensing pathways are used by organisms to respond to, and utilize, organic molecules such as glucose, lipids, and amino acids, in order to generate energy or cellular components.[6,7] Pathways such as the insulin/insulinlike growth factor (IGF-1) pathway, the mechanistic target of the rapamycin (mTOR) pathway, AMP kinase signaling, and sirtuin signaling pathways have been studied in animals and humans for their links between diet and aging processes.[8,9,10,11,12] Through coordination, this network of pathways is able to regulate cell inflammation, autophagy, senescence, and metabolism in response to nutrients, which in turn affects aging.[4,13]

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