Studies On Locomotion Decline Of C.elegans And Its Intervention

With the rapid growth of aging population,how to delay aging,promote health and reduce aging-related diseases has become a hot topic.The model animal Caenorhabditis elegans has been recognized as an excellent model for aging and anti-aging studies because of its short life cycle,distinct aging phenotypes,genetic similarity to human beings and abundant models for age-related diseases.For example,its movement capacity,which is one of the most notable characteristics of aging,decreases with age.And movement capacity is also an important indicator that reflects its overall activity.Therefore,C.elegans was used here as a model to analyze age-related decline of movement capacity with a variety of locomotion parameters.Then a number of lifespan-extending substances,including α-ketoglutarate and abalone peptides,were investigated for their potential intervention on the decline of movement capacity,and abalone peptides were subjected to further studies on its effects against aging and aging-related diseases.1.Lifelong changes of movement capacity and movement capacity relationship with lifespan and reproduction in wild-type C.elegans.First,lifelong crawling and swimming behaviors of C.elegans were analyzed using Movement Tracker and wr MTrck,respectively,and the lifelong monitoring of these movements demonstrated their decline with age.Interestingly,the decline in movement capacity of short-lived C.elegans was found greater than that of long-lived ones.Then,after plotting against age with the movement indicators(crawling speed,swimming speed and thrashing),the area under the curve(AUC)was adopted as a relative measure of lifelong movement capacity.Through correlation analysis between lifelong movement and lifespan,the correlation between swimming ability and lifespan was found to be stronger than the other indicators and showed a linear relationship.However,there was no significant correlation between movement capacity and the number of progeny,or between the number of progeny and lifespan.2.Comparative analysis of movement capacity between wild-type and neurodegenerative disease models.Based on the above movement indicators,comparative analysis was performed between C.elegans proteostasis models,including polyglutamine(poly Q)Huntington’s disease(HD)model and β-amyloid(Aβ)Alzheimer’s disease(AD)model,and wild-type model.In the HD models,the movement capacity of AM141 and AM140 models that expressed poly Q in body wall muscle cells as well as that of HA759 model that expressed poly Q in neurons was adversely affected as compared to wild-type nematodes.The movement capacity of the AD model GMC101,the Aβ expression in which was induced by heat stress,was also decreased significantly.Fitting analysis between movement capacity and age revealed that the decay speed of each locomotion index of the poly Q models was increased,in line with the plateau followed by one phase decay function in the exponential decay function.Based on these results,the poly Q model AM140(at the 5th and10 th day of adult)and Aβ model GMC101(at the 3rd and 5th days after induction)were selected for subsequent activity identification.3.Effects of potential anti-aging substances on the movement capacity of wild-type C.elegans.A number of potential lifespan-extending substances,including α-ketoglutarate,EGCG,abalone peptides,Astragalus polysaccharides,were used to test their effects on the locomotion indicators of wild-type C.elegans.It was found that α-ketoglutarate(4 m M)significantly increased the crawling speed of the nematodes,EGCG(100 μM)significantly increased the swimming speed,and abalone peptides(1 m M and 2 m M)significantly increased the swimming speed on the 10 th day of adulthood.4.Effect of abalone peptides on the movement capacity of wild-type and disease models of C.elegans.Based on the above results,abalone peptides were subjected to further bioactivity tests.It was found that the swimming ability of wild-type C.elegans was significantly increased on the 10 th day of adulthood by abalone peptides at both 1 m M and 2 m M but was only slightly increased on the 15 th day at 2 m M,suggesting that abalone peptides may have better effect to delay the movement decline at an earlier stage of aging.The abalone peptides were also shown to increase the movement capacity of AM140 but had no effect on its lifespan.Furthermore,the abalone peptides were also able to significantly increase the movement capacity of GMC101 on the 5th day after heat stress induction.Together,these results indicate the beneficial effects of abalone peptides on movement disorder caused by aging and protein aggregation.In summary,C.elegans-based movement analysis has a number of advantages such as fast data collection,high experimental efficiency and data objectivity.It can be used to analyze the movement capacity of wildtype nematodes as well as HD,AD or other motor deficit disease models.It can also be used for screening of active substances to improve movement and related conditions,e.g.the beneficial effects of abalone peptides on movement capacity as shown in this study.