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.
MeSH Terms
Aging/physiology
Animals
Caenorhabditis elegans/cytology,genetics,growth & development
Caenorhabditis elegans Proteins/genetics
DNA/genetics
Forkhead Transcription Factors
Longevity
Mitosis
Receptor, Insulin/genetics
Telomere/genetics,ultrastructure
Transcription Factors/genetics
Chemicals
Caenorhabditis elegans Proteins
Forkhead Transcription Factors
Transcription Factors
daf-16 protein, C elegans
DNA
DAF-2 protein, C elegans
Receptor, Insulin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Raices Marcela
The Salk Institute for Biological Studies, La Jolla, California, USA.
Maruyama Hugo
Dillin Andrew
Karlseder Jan
Conflict of Interest
Competing interests. The authors have declared that no competing interests exist.
References (29)
29 references, click to expand
-
A C. elegans mutant that lives twice as long as wild type.
Nature. 1993 Dec 2;366(6454):461-4
PMID: 8247153
-
Thermotolerance of a long-lived mutant of Caenorhabditis elegans.
J Gerontol. 1994 Nov;49(6):B270-6
PMID: 7963273
-
Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress.
Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7540-4
PMID: 7638227
-
Determination of life-span in Caenorhabditis elegans by four clock genes.
Science. 1996 May 17;272(5264):1010-3
PMID: 8638122
-
Telomeric repeats (TTAGGC)n are sufficient for chromosome capping function in Caenorhabditis elegans.
Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8983-8
PMID: 8799140
-
Telomere shortening and tumor formation by mouse cells lacking telomerase RNA.
Cell. 1997 Oct 3;91(1):25-34
PMID: 9335332
-
Extension of life-span by introduction of telomerase into normal human cells.
Science. 1998 Jan 16;279(5349):349-52
PMID: 9454332
-
TRF2 protects human telomeres from end-to-end fusions.
Cell. 1998 Feb 6;92(3):401-13
PMID: 9476899
-
Cell nonautonomy of C. elegans daf-2 function in the regulation of diapause and life span.
Cell. 1998 Oct 16;95(2):199-210
PMID: 9790527
-
Longevity, stress response, and cancer in aging telomerase-deficient mice.
Cell. 1999 Mar 5;96(5):701-12
PMID: 10089885
-
Accelerated telomere shortening in response to life stress.
Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17312-5
PMID: 15574496
-
Somatic polyploidization and cellular proliferation drive body size evolution in nematodes.
Proc Natl Acad Sci U S A. 2000 May 9;97(10):5285-90
PMID: 10805788
-
MRT-2 checkpoint protein is required for germline immortality and telomere replication in C. elegans.
Nature. 2000 Jan 13;403(6766):159-64
PMID: 10646593
-
Wild-derived inbred mouse strains have short telomeres.
Nucleic Acids Res. 2000 Nov 15;28(22):4474-8
PMID: 11071935
-
Hayflick, his limit, and cellular ageing.
Nat Rev Mol Cell Biol. 2000 Oct;1(1):72-6
PMID: 11413492
-
C. elegans RAD-5/CLK-2 defines a new DNA damage checkpoint protein.
Curr Biol. 2001 Dec 11;11(24):1934-44
PMID: 11747819
-
Protection of mammalian telomeres.
Oncogene. 2002 Jan 21;21(4):532-40
PMID: 11850778
-
Senescence induced by altered telomere state, not telomere loss.
Science. 2002 Mar 29;295(5564):2446-9
PMID: 11923537
-
Genetic analysis of tissue aging in Caenorhabditis elegans: a role for heat-shock factor and bacterial proliferation.
Genetics. 2002 Jul;161(3):1101-12
PMID: 12136014
-
Rates of behavior and aging specified by mitochondrial function during development.
Science. 2002 Dec 20;298(5602):2398-401
PMID: 12471266
-
Regulation of aging and age-related disease by DAF-16 and heat-shock factor.
Science. 2003 May 16;300(5622):1142-5
PMID: 12750521
-
Sequence-specific binding to telomeric DNA by CEH-37, a homeodomain protein in the nematode Caenorhabditis elegans.
J Biol Chem. 2003 Jul 25;278(30):28038-44
PMID: 12711598
-
Identification of HMG-5 as a double-stranded telomeric DNA-binding protein in the nematode Caenorhabditis elegans.
FEBS Lett. 2003 Nov 20;554(3):455-61
PMID: 14623111
-
Long lifespan in worms with long telomeric DNA.
Nat Genet. 2004 Jun;36(6):607-11
PMID: 15122256
-
Strain-specific telomere length revealed by single telomere length analysis in Caenorhabditis elegans.
Nucleic Acids Res. 2004;32(11):3383-91
PMID: 15247331
-
The genetics of Caenorhabditis elegans.
Genetics. 1974 May;77(1):71-94
PMID: 4366476
-
A single-stranded telomere binding protein in the nematode Caenorhabditis elegans.
FEBS Lett. 2001 Sep 14;505(2):301-6
PMID: 11566194
-
The C. elegans maternal-effect gene clk-2 is essential for embryonic development, encodes a protein homologous to yeast Tel2p and affects telomere length.
Development. 2001 Oct;128(20):4045-55
PMID: 11641227
-
C. elegans clk-2, a gene that limits life span, encodes a telomere length regulator similar to yeast telomere binding protein Tel2p.
Curr Biol. 2001 Oct 30;11(21):1706-10
PMID: 11696330