Gene-diet interactions and aging in C. elegans

Abstract

Diet is the most variable aspect of life history, as most individuals have a large diversity of food choices, varying in the type and amount that they ingest. In the short-term, diet can affect metabolism and energy levels. However, in the long run, the net deficiency or excess of calories from diet can influence the progression and severity of age-related diseases. An old and yet still debated question is: how do specific dietary choices impact health- and lifespan? It is clear that genetics can play a critical role — perhaps just as important as diet choices. For example, poor diet in combination with genetic susceptibility can lead to metabolic disorders, such as obesity and type 2 diabetes. Recent work in Caenorhabditis elegans has identified the existence of diet-gene pairs, where the consequence of mutating a specific gene is only realized on specific diets. Many core metabolic pathways are conserved from worm to human. Although only a handful of these diet-gene pairs has been characterized, there are potentially hundreds, if not thousands, of such interactions, which may explain the variability in the rates of aging in humans and the incidence and severity of age-related diseases.

Gene-by-environmental modulation of longevity and weight gain in the murine BXD family

“…For example, studies exploiting Mendelian randomization have not shown a compelling causal link between triglyceride levels on longevity in humans (Liu et al, 2017). In general, a diet high in fat leads to obesity and reduced lifespan in diverse species including Drosophila, C. elegans and mice (Otabe et al, 2007), (Yen and Curran, 2016), (Gáliková and Klepsatel, 2018). However, consumption of high levels of corn oil rich in poly-and monounsaturated fats (58.6% fat-derived calories) in C57BL/6 male mice has been shown to improve health and longevity, provided that total calorie consumption stays within normal bounds (Si et al, 2014).…”

Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease

“…Additionally, the discrepancies between sex, or strain variations in sensing and handling of substrates, may convolute the interpretation of data derived from animal model systems ( 304 ). Differences in experimental approaches and the techniques used to measure metabolic flexibility may influence outcomes ( 305 ). Methodological differences can severely impact interpretation of study data ( 106 ), advocating for a gold-standard application of available methods and technology.…”

Treatment of Caenorhabditis elegans with Small Selenium Species Enhances Antioxidant Defense Systems

“…In recent years, a growing body of research on dietary restriction, food choice, nutrient intake, and gene‐diet interactions has been conducted in C. elegans , demonstrating among other things how diet can have long‐lasting effects on animal physiology and even influence future generations (reviewed in ref. ). In this context, the current study aimed to address the question if supplementation with Se species in an early life stage has long‐term protective effects after supplementation is ceased.…”

“…The alternative and complementary in vivo model C. elegans is commonly used in mechanistic studies in toxicological, biomedical, and aging research, due to its rapid life cycle, genetic manipulability, and high degree of evolutionary conserved genes and pathways . Many core metabolic pathways are conserved between humans and C. elegans , including the insulin/IGF‐1, AMPK, and TOR pathways, as well as transcription factors and nuclear hormone receptors involved in lipid and energy homeostasis . In addition to being a well‐established model for neurodegenerative diseases, C. elegans applications to study metabolic disorders, such as diabetes or obesity are available as well (summarized in refs.…”