Telomere biology and cellular aging in nonhuman primate cells.

To determine how cellular aging is conserved among primates, we analyzed the replicative potential and telomere shortening in skin fibroblasts of anthropoids and prosimians. The average telomere length of the New World primates Ateles geoffroyi (spider monkey) and Saimiri sciureus (squirrel monkey) and the Old World primates Macaca mulatta (rhesus monkey), Pongo pygmaeus (orangutan), and Pan paniscus (pigmy chimpanzee) ranged from 4 to 16 kb. We found that telomere shortening limits the replicative capacity of anthropoid fibroblasts and that the expression of human telomerase produced telomere elongation and the extension of their in vitro life span. In contrast the prosimian Lemur catta (ring-tailed lemur) had both long and short telomeres and telomere shortening did not provide an absolute barrier to immortalization. Following a transient growth arrest a subset of cells showing a reduced number of chromosomes overgrew the cultures without activation of telomerase. Here we show that the presence of continuous TTAGGG repeats at telomeres and rigorous control of replicative aging by telomere shortening appear to be conserved among anthropoid primates but is less effective in prosimian lemurs.

[1]  Y. Kawamoto,et al.  PRINS Analysis of the Telomeric Sequence in Seven Lemurs , 2004, Chromosome Research.

[2]  J. Shay,et al.  Telomerase Can Inhibit the Recombination-based Pathway of Telomere Maintenance in Human Cells* , 2001, The Journal of Biological Chemistry.

[3]  M. Hande,et al.  Extra-chromosomal telomeric DNA in cells from Atm(-/-) mice and patients with ataxia-telangiectasia. , 2001, Human molecular genetics.

[4]  J. Shay,et al.  Cellular senescence as a tumor-protection mechanism: the essential role of counting. , 2001, Current opinion in genetics & development.

[5]  R. DePinho,et al.  Cellular Senescence Minireview Mitotic Clock or Culture Shock? , 2000, Cell.

[6]  J. Shay,et al.  Telomere dynamics in cancer progression and prevention: fundamental differences in human and mouse telomere biology , 2000, Nature Medicine.

[7]  Heidi S. Liss,et al.  Subsenescent Telomere Lengths in Fibroblasts Immortalized by Limiting Amounts of Telomerase* , 2000, The Journal of Biological Chemistry.

[8]  P. Hornsby,et al.  Formation of functional tissue from transplanted adrenocortical cells expressing telomerase reverse transcriptase , 2000, Nature Biotechnology.

[9]  A. Hasegawa,et al.  Measurement of telomerase activity in dog tumors. , 1999, The Journal of veterinary medical science.

[10]  T. Ide,et al.  Human is a unique species among primates in terms of telomere length. , 1999, Biochemical and biophysical research communications.

[11]  David Waddington,et al.  Analysis of telomere lengths in cloned sheep , 1999, Nature.

[12]  J. Shay,et al.  Telomerase activity does not always imply telomere maintenance. , 1999, Biochemical and biophysical research communications.

[13]  R. Venkatesan,et al.  Telomerase expression in chickens: constitutive activity in somatic tissues and down-regulation in culture. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[14]  S. Benchimol,et al.  Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicative life span , 1998, Current Biology.

[15]  C. Harley,et al.  Extension of life-span by introduction of telomerase into normal human cells. , 1998, Science.

[16]  J. Shay,et al.  Normal human chromosomes have long G-rich telomeric overhangs at one end. , 1997, Genes & development.

[17]  R. Verma,et al.  Physical mapping of human 7q and 14q subtelomeric DNA sequences in the great apes. , 1997, DNA research : an international journal for rapid publication of reports on genes and genomes.

[18]  J. Shay,et al.  Comparison of the telomeric repeat amplification protocol (TRAP) to the new TRAP-eze telomerase detection kit , 1996 .

[19]  I. Gustavsson,et al.  Localization of the telomeric (TTAGGG)n sequences in chromosomes of some domestic animals by fluorescence in situ hybridization. , 2004, Hereditas.

[20]  W. Wertelecki,et al.  Telomeres of higher primates. , 1995, Biochemistry and molecular biology international.

[21]  M. Blasco,et al.  Functional characterization and developmental regulation of mouse telomerase RNA , 1995, Science.

[22]  P. Rogalla,et al.  Two human breast cancer cell lines showing decreasing telomeric repeat length during early in vitro passaging. , 1994, Cancer genetics and cytogenetics.

[23]  A. Jeffreys,et al.  A subterminal satellite located adjacent to telomeres in chimpanzees is absent from the human genome , 1994, Nature Genetics.

[24]  C B Harley,et al.  Telomere length predicts replicative capacity of human fibroblasts. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[25]  C. Harley,et al.  Telomeres shorten during ageing of human fibroblasts , 1990, Nature.

[26]  D. Loo,et al.  Extended culture of mouse embryo cells without senescence: inhibition by serum. , 1987, Science.

[27]  A M Olovnikov,et al.  A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. , 1973, Journal of theoretical biology.

[28]  J. D. Watson Origin of Concatemeric T7DNA , 1972 .

[29]  L. Hayflick THE LIMITED IN VITRO LIFETIME OF HUMAN DIPLOID CELL STRAINS. , 1965, Experimental cell research.

[30]  L. Hayflick,et al.  The serial cultivation of human diploid cell strains. , 1961, Experimental cell research.