Uncoupling of Longevity and Telomere Length in C. elegans

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Abstract
The nematode Caenorhabditis elegans, after completing its developmental stages and a brief reproductive period, spends the remainder of its adult life as an organism consisting exclusively of post-mitotic cells. Here we show that telomere length varies considerably in clonal populations of wild-type worms, and that these length differences are conserved over at least ten generations, suggesting a length regulation mechanism in cis. This observation is strengthened by the finding that the bulk telomere length in different worm strains varies considerably. Despite the close correlation of telomere length and clonal cellular senescence in mammalian cells, nematodes with long telomeres were neither long lived, nor did worm populations with comparably short telomeres exhibit a shorter life span. Conversely, long-lived daf-2 and short-lived daf-16 mutant animals can have either long or short telomeres. Telomere length of post-mitotic cells did not change during the aging process, and the response of animals to stress was found independent of telomere length. Collectively, our data indicate that telomere length and life span can be uncoupled in a post-mitotic setting, suggesting separate pathways for replication-dependent and -independent aging. The worm Caenorhabditis elegans has historically been used as a powerful model to study organismal aging. After a brief reproductive period, an adult worm consists of 959 post-mitotic cells. Telomeres, the natural ends of linear chromosomes, have long been implicated in the aging process of mitotic cells, and telomere shortening has been proposed to be a limiting factor in cell division. The authors show that telomere length of C. elegans chromosomes is independent of organismal aging. Worm telomeres were characterized in detail, and found to vary considerably in individual clones. These differences were conserved over several populations, suggesting that telomere length is controlled by similar mechanisms in worms and mammals, emphasizing the value of C. elegans as a model for telomere biology. However, telomere length has not been found to determine the potential life span of the animals, since worms with short telomeres lived as long as worms with long telomeres. Vice versa, worms that have an altered life span due to mutations in the insulin receptor pathway do not show any changes in telomere length. Telomere length was also found to be constant in isolated, aging worm populations, suggesting that organismal aging can be uncoupled from mitotic aging.