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Uncoupling of longevity and telomere length in C. elegans - PubMed

Uncoupling of longevity and telomere length in C. elegans

Marcela Raices et al. PLoS Genet. 2005 Sep.

Erratum in

  • PLoS Genet. 2005 Dec;1(6):e81

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.

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Conflict of interest statement

Competing interests. The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Clonal Variation and Conservation of Telomere Length in C. elegans

(A) AluI/MboI digests of genomic DNA from six Bristol N2 clones was separated by gel electrophoresis and hybridized with (TTAGGC)4 or (GCCTAA)4 probes as described [28]. Fragment size is indicated in kb, and internal repeats are indicated by an asterisk. (B) DNA from six individual N2 clones was incubated with Bal31 for the indicated time, and then processed as in (A). (C) Six individual N2 clones were propagated for ten generations, and telomere length was determined as described. (D) Seven different C. elegans strains were examined for their telomere length as described in (A).

Figure 2
Figure 2. Organismal Life Span Is Independent of Telomere Length

(A) Life span of N2 worms under control (green), daf-2 (blue), and daf-16 (red) RNAi suppression conditions. Worms were grown on bacteria expressing RNAi constructs targeting the indicated genes, and life span was assessed as described [21]. (B) Telomere length of nine individual control N2 clones was assessed as described. Samples were collected at the beginning (B) and end (E) of the experiment, and fragment size is indicated in kb. (C) Telomere length of nine individual daf-2 (RNAi) N2 clones was assessed as described in (B). (D) Telomere length of nine individual daf-16 (RNAi) N2 clones was assessed as described in (B).

Figure 3
Figure 3. Telomere Length Is Independent from Organismal Life Span and Thermo Tolerance

(A) CF512 temperature-sensitive sterile worms were grown at 25 °C, and life span was monitored. Samples were taken at indicated times. (B) DNA from CF512 temperature-sensitive sterile worms was extracted at the indicated time points, and telomere length was monitored in mixed and synchronous populations (for details, see Materials and Methods). Telomere length is indicated in kb. The asterisk points out a variable band-like signal resulting from gel drying. (C) Seven different worm strains and daf-2 and daf-16 RNAi suppressed worms (indicated in different colors) with genetically determined telomere length (Figure 1D) were subjected to heat treatment as described [31]. Survival was assessed at the indicated time points. (D) Two worm strains with long telomeres (CC2, TR403) and N2 worms with short telomeres were subjected to daf-16 suppression by RNAi. Life spans were determined as described.

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