Effects of High Dietary Carbohydrate and Lipid Intake on the Lifespan of C. elegans

Abstract

Health and lifespan are influenced by dietary nutrients, whose balance is dependent on the supply or demand of each organism. Many studies have shown that an increased carbohydrate-lipid intake plays a critical role in metabolic dysregulation, which impacts longevity. Caenorhabditis elegans has been successfully used as an in vivo model to study the effects of several factors, such as genetic, environmental, diet, and lifestyle factors, on the molecular mechanisms that have been linked to healthspan, lifespan, and the aging process. There is evidence showing the causative effects of high glucose on lifespan in different diabetic models; however, the precise biological mechanisms affected by dietary nutrients, specifically carbohydrates and lipids, as well as their links with lifespan and longevity, remain unknown. Here, we provide an overview of the deleterious effects caused by high-carbohydrate and high-lipid diets, as well as the molecular signals that affect the lifespan of C. elegans; thus, understanding the detailed molecular mechanisms of high-glucose- and lipid-induced changes in whole organisms would allow the targeting of key regulatory factors to ameliorate metabolic disorders and age-related diseases.

Keywords: C. elegans; carbohydrate; lifespan; lipids; transcription factors and metabolism.

Figure 1

Caenorhabditis elegans as a model organism to study the effects of high-carbohydrate and high-fat diets on the lifespan. C. elegans offers many technical and biological advantages, since it has been shown that develops many of the cellular and molecular alterations reported in humans caused by overconsumption of sugars and lipids.

Figure 2

Effects of high glucose in C. elegans. Under standard feeding conditions, genetic inhibition of several glycolytic enzymes increases lifespan (left). Exposure to high dietary glucose reduces the lifespan; however, genetic blocks of GPI and ALDO glycolytic genes protect against high-glucose-induced shortened lifespan. GPI, glucose phosphate isomerase; PFK, phosphofructokinase; ALDO, fructose-1,6-bisphosphate aldolase; PGAM, phosphoglycerate mutase; PYK, pyruvate kinase; FGT-1, facilitated glucose transporter -1).

Figure 3

Dietary glucose decreases lifespan by altering cellular localization of several transcriptional factors. High glucose, probably through activation of the IIS pathway, diminishes the nuclear localization and transcriptional activity of DAF-16/FOXO and SKN-1, which consequently decreases the worms’ lifespan. Interestingly, high glucose augments the nuclear localization of HLH-30 and SBP-1/MDT-15, although with opposite consequences, because HLH-30 decreases the lifespan whereas SBP-1/MDT-15 prevents the life-shortening effects of high glucose.

Figure 4

Effects of different dietary lipids on the lifespan of C. elegans. Exogenous MUFAs and PUFAs contribute to lifespan extension via activation of several transcriptional factors that promote gene transcription of enzymes for fatty acid desaturation, which might play an important role in the positive regulation of the lifespan.

Figure 5

The schematic represents a simplified overview of the signaling pathways regulating organismal lifespan under the influence of drugs.