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Abstract
Aging is an inevitable time-dependent process involving degenerative physiological alterations in tissues and organs that increase the susceptibility to various chronic diseases and eventually lead to death. The aging studies focus on lifespan, but more recently research on healthspan to improve the quality of life during aging has emerged. Aging is a common process for all animal species; however, due to the limitation of time in aging study, Caenorhabditis elegans,a eukaryotic, multi-organ nematode, is considered the premier choice model system for the study of aging. Like humans, C. elegans expresses degenerative muscle functions due to aging. This study determined the lifespan regulation effect of natural compounds and pharmaceutical compound in C. elegans.
Coffee is one of the most widely consumed beverages and is known to have many health benefits. Our previous study reported that kahweol, a diterpene found in coffee, reduced fat accumulation by reducing food intake in Caenorhabditis elegans. Kahweol significantly extended the lifespan of wild-type C. elegans. However, kahweol increased the lifespan of the eat-2 null mutant that has a reduced food intake phenotype, suggesting that kahweol extends lifespan independent of reduced food intake. Therefore, we further determine the target of kahweol on lifespan extension. Kahweol had no effects on the lifespan of both daf-2 (the homolog of insulin/insulin-like growth factor-1 receptor) and daf-16 (the homolog of Forkhead box O transcription factor and a major downstream target of daf-2) null mutants, suggesting kahweol extended lifespan via insulin/insulin-like growth factor-1 signaling pathway. In addition, kahweol failed to extend lifespan in tub-1 (the homolog of TUB bipartite transcription factor) and aak-2 (the homolog of AMP-activated protein kinase) null mutants, suggesting these roles on kahweol’s effect on lifespan. However, the treatment of kahweol increased the lifespan in sir-2.1 (the homolog of NAD-dependent deacetylase sirtuin-1) and skn-1(the homolog of nuclear factor erythroid 2-related factor 2) null mutants over the control, suggesting independent functions of these genes on kahweol’s lifespan extension.
Cannabis, also known as marijuana, has been resurging its interest for its potential medical properties as well as recreational usages. Cannabinoid receptor type 1 and 2 (CB1R and CB2R, respectively) were discovered as the target of the main psychotropic effects of marijuana, which is a part of the endocannabinoid system, composed of endocannabinoids, cannabinoid receptors, and their metabolic enzymes. It has been reported that CB1R contributes to obesity and its metabolic consequences, and CB1R antagonism in mice reversed age-related insulin resistance and metabolic dysregulations. Treatment of ACEA (arachidonyl-2’-chloroethylamide, a highly selective agonist of cannabinoid receptor type 1) significantly reduced lifespan, 13% over the control, p=0.0032. Meanwhile, treatment ofrimonabant (a selective inverse agonist of cannabinoid receptor type 1) extended lifespan, 15% increase over the control, p=0.042. Treatment of either ACEA and rimonabant did not show significant effect in daf-2, daf-16, aak-1, sir-2.1, and skn-1 null mutants. However, only rimonabant did not show lifespan extension effect in aak-2 null mutant.
We further evaluated various markers of muscle functions and determined that bending or pharyngeal pumping rate can be used to represent the healthiness of nematodes. The quantified health-related metrics data were applied to set up a method to determine the healthiness of C. elegans.
Type
Dissertation (Campus Access - 5 Years)
Date
2024-05
Publisher
Degree
Advisors
License
Attribution 4.0 International
License
http://creativecommons.org/licenses/by/4.0/
Research Projects
Organizational Units
Journal Issue
Embargo Lift Date
2025-05-17