Study of Lipofuscin Accumulation and Removal in Caenorhabditis elegans for Age-Related Degeneration

Abstract

The accumulation of misfolded or aggregated proteins in aging animals has been considered one of the causes of neurodegenerative diseases When the damaged proteins further aggregate with other waste materials such as lipid and metals they will form a complex which is well known as Lipofuscin (LF) LF is usually considered a cytotoxic material due to highly oxidative stress However it remains difficulty to observe the LF granules in live animals to date due to the limitation of the current technology As a result Caenorhabditis (C ) elegans is used as a model animal in this thesis C elegans has been widely used as a model organism for fundamental biological research due to its potential in developmental biology genetics and neuroscience It is known that HSPs can function as molecular chaperones as well as “dustmen” in cells In this research we developed a novel addressable heating technique based on an optoelectric device to induce heat shock proteins (HSPs) to scavenge the LF granules Heat shock response is a protective mechanism typically induced by heat that helps animals to survive in harsh environments In the thesis the wild-type worms (N2) and the transgenic worms SJ4005 (HSP-4::GFP) and CL2070 (HSP-16 2::GFP) were investigated The experimental conditions included induction of HSPs LF accumulation of feeding olanzapine which is an antipsychotic drug but has a side effect on lipid-increasing suppressing the expression of HSPs by RNAi technique and oxidative stress measurement The results showed that induction of HSPs decreased LF accumulation and the number of progeny but extended lifespan of worms Meanwhile exploring the effects of LF on aging feeding olanzapine caused the increase of LF accumulation yet the decreases of lifespan and progeny Furthermore suppressing the expression of HSPs by RNAi technique proves the importance of the LF removal Applying to optoelectric or olanzapine treatment compares the results of LF accumulation lifespan and numbers of progeny The results showed that inhibiting HSPs makes LF accumulation increase lifespan decrease and progeny decline Besides the hypothesis of increasing LF is oxidative stress raised The result shows that there is a positive correlation between the LF accumulation and ROS In the future optoelectric treatment will be applied for Alzheimer’s worms We hope that inducing HSPs could decrease LF accumulation extend lifespan and improve the swimming gait As last the success of the results may provide a potential impact to the active treatments in age-related diseases

Date of Award	2014 Aug 29
Original language	English
Supervisor	Han-Sheng Chuang (Supervisor)