Protective Effects of Transient Glucose Exposure in Adult C. elegans

Abstract

C. elegans are used to study molecular pathways, linking high glucose levels (HG) to diabetic complications. Persistent exposure of C. elegans to a HG environment induces the mitochondrial formation of reactive oxygen species (ROS) and advanced glycation endproducts (AGEs), leading to neuronal damage and decreased lifespan. Studies suggest that transient high glucose exposure (TGE) exerts different effects than persistent exposure. Thus, the effects of TGE on ROS, AGE-formation and life span were studied in C. elegans. Four-day TGE (400 mM) as compared to controls (0mM) showed a persistent increase of ROS (4-days 286 ± 40 RLUs vs. control 187 ± 23 RLUs) without increased formation of AGEs. TGE increased body motility (1-day 0.14 ± 0.02; 4-days 0.15 ± 0.01; 6-days 0.16 ± 0.02 vs. control 0.10 ± 0.02 in mm/s), and bending angle (1-day 17.7 ± 1.55; 3-days 18.7 ± 1.39; 6-days 20.3 ± 0.61 vs. control 15.3 ± 1.63 in degree/s) as signs of neuronal damage. Lifespan was increased by 27% (21 ± 2.4 days) after one-day TGE, 34% (22 ± 1.2 days) after four-days TGE, and 26% (21 ± 1.4 days) after six-days TGE vs. control (16 ± 1.3 days). These experiments suggest that TGE in C. elegans has positive effects on life span and neuronal function, associated with mildly increased ROS-formation. From the perspective of metabolic memory, hormetic effects outweighed the detrimental effects of a HG environment.

Naringin Alleviates Glucose-Induced Aging by Reducing Fat Accumulation and Promoting Autophagy in Caenorhabditis elegans

“…Thus, we speculated that Nar might inhibit the enzymes involved in glucose metabolism to interfere with the toxic effects of glucose. This mechanism, however, as the concentration of Nar increases, will lead to an increase in free glucose, enhancing the nonenzymatic reactions of glucose with proteins and nucleic acids to form advanced glycation-end products, ultimately shortening the lifespan of the nematode [ 61 ].…”

The unfolded protein response reverses the effects of glucose on lifespan in chemically-sterilized C. elegans

“…Our study points to a specific life stage from which it could be beneficial to promote artificial proteostasis and subsequently attenuate the consequences of ageing. Interestingly, animals subjected to HGD at the pre-reproductive stage or short HGD exposure in young adults have been reported to extend lifespan 72,73 . The timing and length for intervention might be critical, as it could exacerbate ageing if done unduly early and persistently.…”

Glucose-Induced Developmental Delay is Modulated by Insulin Signaling and Exacerbated in Subsequent Glucose-Fed Generations in Caenorhabditis elegans

“…Elevated glucose concentrations have notable consequences, including the diversion of excess glucose-6phosphate into the hexosamine pathway. This metabolic shift can lead to the production of methylglyoxal and advanced glycated end products (AGEs), which have been associated with shortening of lifespan (Schlotterer et al 2009;Seo et al 2018;Murillo et al 2022). These AGEs often form due to the glycation of proteins and lipids, particularly in oligosaccharides consisting of more than two but less than eleven monosaccharide units.…”

“…These AGEs often form due to the glycation of proteins and lipids, particularly in oligosaccharides consisting of more than two but less than eleven monosaccharide units. The accumulation of AGEs is a natural component of the aging process, and dietary glucose supplementation has been shown to increase their accumulation in C. elegans (Schlotterer et al 2009;Seo et al 2018;Murillo et al 2022).…”