Yanase, Sumino et al. (2021) International Worm Meeting "Recovery of Muscle Function Dependent on the Impaired Cell Death in a C. elegans Premature Aging Model"

Suzuki, Yu, Yasuda, Kayo, Ishii, Naoaki, Yanase, Sumino, Sekigawa, Kota, Otsuka, Yuko

[International Worm Meeting, 2021]

In mammals including humans, the age-related losses of muscle mass and function are known as sarcopenia. Although the mechanisms underlying the development of sarcopenia are multifactorial, apoptosis has been shown to play a role in muscle loss during aging [1]. Recently, age-related muscle loss has also been found in the nematode C. elegans during normal aging. As in humans, age-related muscle loss in C. elegans leads to decreased mobility and serves as a marker for increased mortality [2, 3]. Here we examined the difference in age-associated pharyngeal muscle function between the short-lived mev-1(kn1) and the phenotype of deficient cell death (mev-1;ced-3 mutant), however, have shown no significant histopathological change in the loss of pharyngeal muscle mass. The mev-1 gene encodes a large subunit of the enzyme succinate dehydrogenase cytochrome b, which is a component of complex II in the mitochondrial electron transport chain. Mutation of the gene causes an increase in mitochondrial oxidative stress, thereby induces abnormal apoptosis in embryonic development and shortenes the lifespan [4]. Moreover, we aim to detect age-related difference in gene expression concerned with the cell death signaling using both mutants. References 1. Always SE et al. (2011) Aging and apoptosis in muscle, In: Handbook of the biology of aging, 7th edition (eds. Masoro EJ, Austad SN), Academic Press, London, pp. 63-118 2. Herndon LA et al. (2002) Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans, Nature 419: 808-814 3. Fishen AL (2004) Of worms and women: Sarcopenia and its role in disability and mortality, J Am Geriatr Soc 52: 1185-1190 4. Ishii N et al. (1998) A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes. Nature 394: 694-697

Claire Benard et al. (2001) International C. elegans Meeting "The maternal-effect gene clk-2 affects developmental timing, is essential for embryonic development, encodes a protein homologous to yeast Tel2p, and is required for telomere length regulation in C. elegans."

Yue Zhang, Bernard Lakowski, Stephanie Felkai, Claire Benard, Siegfried Hekimi, Brent McCright

[International C. elegans Meeting, 2001]

The C. elegans maternal-effect clk genes are involved in the temporal control of development and behavior, and participate in life-span determination 1,2 . We will present our detailed genetic and molecular characterization of clk-2 . A temperature-sensitive mutation of clk-2 affects embryonic and post-embryonic development, reproduction, adult behaviors, and life span, yet virtually all phenotypes can be fully maternally rescued. Genetic interactions of clk-2 with other genes that affect life span indicate that clk-2 acts independently of the genetic pathway that regulates dauer formation, and that clk-2 increases life span by a mechanism that resembles caloric restriction. While clk-2 is required throughout the life cycle, including for fertility, embryonic development strictly requires the activity of maternal clk-2 during a narrow time window between oocyte maturation and the 2 to 4-cell stage. Positional cloning of clk-2 reveals that it encodes a protein homologous to S. cerevisiae Tel2p. In yeast, the gene TEL2 positively regulates telomere length, participates in gene silencing at subtelomeric regions, and Tel2p binds to telomeric repeats in vitro 3,4 . The gene clk-2 is required for telomere length regulation in C. elegans , since clk-2 mutants have elongated telomeres, and clk-2 overexpression can lead to telomere shortening. CLK-2 is expressed throughout development and high clk-2 transcript levels are present in the germline. We are currently exploring the relationships between the variety of clk-2 phenotypes and whether the maternal effect is the result of epigenetic mechanisms comparable to subtelomeric silencing. References: 1. Hekimi S, Boutis P, Lakowski B. Viable maternal-effect mutations that affect the development of the nematode Caenorhabditis elegans . Genetics 1995, 141(4):1351-64. 2. Lakowski B, Hekimi S. Determination of life-span in Caenorhabditis elegans by four clock genes. Science 1996, 272(5264):1010-3. 3. Runge K, Zakian, V. TEL2 , an essential gene required for telomere length regulation and telomere position effect in Saccharomyces cerevisiae. Molecular and Cellular Biology. 1996, 16(6):3094-3105. 4. Kota R, Runge K. The yeast telomere length regulator TEL2 encodes a protein that binds to telomeric DNA. Nucleic Acids Research 1998, 26(6):1528-35.