Thomas E. Johnson, Ph.D.
“The plasticity of ageing suggests that longevity may be controlled epigenetically by specific alterations in chromatin state” (Greer and Brunet, 2010). Epigenetics, in a broad sense, is a bridge between genotype and phenotype—a phenomenon that changes the final effect of a locus or chromosome without changing the underlying DNA sequence. This project reviews research performed by Greer and Brunet, (2010), Hamilton et al., (2013), and Lee et al., (2008), that involved the use of RNAi to modify an epigenetic effect on the lifespan of the soil nematode C. elegans. RNA interference (RNAi) was used to regulate lifespan in C. elegans by causing deficiencies in methylation of histone H3 at lysine 4 (H3K4). While the previously mentioned authors observed extended lifespan in C. elegans treated with RNAi, neither study considered the quality of health of the animals with extended lifespan. Herein, methods used in previous studies were replicated to produce long-lived C. elegans, but the focus was quantifying the healthspan of the animals. Healthspan is a novel term in research that describes the length of a healthy life. When considering lifespan-extending treatments we must consider “healthspan”- the healthy adult period of unimpaired life that precedes functional decline (Herndon et al., 2002). A key question is whether the increasing proportion of the population surviving to advanced ages will display continued quality of existence, which can be defined as delayed onset of chronic illness and physical/mental decline. Experimental animals were classified into four categories that reflect health based on frequency of movement. Upon analysis of the data, it appears that mutations for genes wdr-5.1 and set-4, and RNAi-mediated knock down of set-2 produced an improved heatlhspan:lifespan ratio. However RNAi-mediated knock down of genes wdr-5.1, set-9, set-15, and set-18 did not improve the healthspan:lifespan ratio.
Beverly, Lindsey, "Assessing Healthspan in Long Lived C. elegans" (2013). Undergraduate Honors Theses. 398.