M., Spector, T.D.,

The effects of social status on biological aging as measured by white-blood-cell telomere length. Aging Cell

,

–

Codd, V., Mangino, M., van der Harst, P., Braund, P.S., Kaiser, M., Beveridge, A.J., Rafelt, S., Moore, J., Nelson, C., Soranzo, N., Zhai, G., Valdes, A.M., Blackburn, H., Mateo Leach, I., de Boer, R.A., Kimura, M., Aviv, A., Goodall, A.H., Ouwehand, W., van Veldhuisen, D.J., van Gilst, W.H., Navis, G., Burton, P.R., Tobin, M.D., Hall, A.S., Thompson, J.R., Spector, T., Samani, N.J.,

Common variants near TERC are associated with mean telo- mere length. Nat. Genet.

,

–

Cohen, S.B., Graham, M.E., Lovrecz, G.O., Bache, N., Robinson, P.J., Reddel, R.R.,

Protein composition of catalytically active human telomerase from immortal cells. Science

,

–

Conrad,D.F.,Pinto,D.,Redon,R.,Feuk,L.,Gokcumen,O.,Zhang,Y.,Aerts,J.,Andrews,T.D., Barnes, C., Campbell, P., Fitzgerald, T., Hu, M., Ihm, C.H., Kristiansson, K., Macarthur, D.G., Macdonald, J.R., Onyiah, I., Pang, A.W., Robson, S., Stirrups, K., Valsesia, A., Walter, K., Wei, J., Wellcome Trust Case Control Consortium, Tyler-Smith, C., Carter, N.P., Lee, C., Scherer, S.W., Hurles, M.E.,

Origins and functional impact of copy number variation in the human genome. Nature

,

–

De Benedictis, G., Carotenuto, L., Carrieri, G., De Luca, M., Falcone, E., Rose, G., Yashin, A.I., Bonafè, M., Franceschi, C.,

Age-related changes of the

′APOB-VNTR ge- notype pool in ageing cohorts. Ann. Hum. Genet.

,

–

De Rango, F., Montesanto, A., Berardelli, M., Mazzei, B., Mari, V., Lattanzio, F., Corsonello, A., Passarino, G.,

To grow old in southern Italy: a comprehensive description of the old and oldest old in Calabria. Gerontology

,

–

El-Sayed Moustafa, J.S., Eleftherohorinou, H., de Smith, A.J., Andersson-Assarsson, J.C., Alves, A.C., Hadjigeorgiou, E., Walters, R.G., Asher, J.E., Bottolo, L., Buxton, J.L., Sladek, R., Meyre, D., Dina, C., Visvikis-Siest, S., Jacobson, P., Sjostrom, L., Carlsson, L.M., Walley, A., Falchi, M., Froguel, P., Blakemore, A.I., Coin, L.J.,

Novel asso- ciation approach for variable number tandem repeats (VNTRs) identifies DOCK

as a susceptibility gene for severe obesity. Hum. Mol. Genet.

,

–

Epel, E.S., Blackburn, E.H., Lin, J., Dhabhar, F.S., Adler, N.E., Morrow, J.D., Cawthon, R.M.,

Accelerated telomere shortening in response to life stress. Proc. Natl. Acad. Sci. U. S. A.

,

–

Gomes, N.M., Ryder, O.A., Houck, M.L., Charter, S.J., Walker, W., Forsyth, N.R., Austad, S.N., Venditti, C., Pagel, M., Shay, J.W., Wright, W.E.,

Comparative biology of mammalian telomeres: hypotheses on ancestral states and the roles of telomeres in longevity determination. Aging Cell

,

–

Herskind, A.M., M

ue, M., Holm, N.V., Sorensen, T.I., Harvald, B., Vaupel, J.W.,

The heritability of human longevity: a population-based study of

Danish twin pairs born

–

Hum. Genet.

,

–

Hofer, P., Baierl, A., Feik, E., Fuhrlinger, G., Leeb, G., Mach, K., Holzmann, K., Micksche,

In conclusion, this is the first study reporting the association be- tween the functional VNTR MNS16A of TERT and human longevity. Our study provides interesting findings that should be investigated in different populations and in larger samples (for LTL). The crucial role played by TERT and telomere dynamics in aging process is warranted by many established functions of this enzyme and its involvement in several age-related diseases, so we further underscore the need of fur- ther investigations to definitively address the role of TERT variants in the regulation of human life-span.

Supplementary data to this article can be found online at http:// dx.doi.org/10.1016/j.exger.2013.03.009.

Conflict of interest

The authors have no conflict to declare.

Acknowledgments

This workwassupported byItalianMinistry forUniversity, Scientific and Technology (PRIN 2008-prot. 20089MANHH_002).

We also thank Dr. Richard M. Cawthon for his advices about the protocol for telomere length measurement, and Elisa Fratini for data analysis.

References

Armanios, M., Blackburn, E.H., 2012. The telomere syndromes. Nat. Rev. Genet. 13,

Atzmon, G., Cho, M., Cawthon, R.M., Budagov, T., Katz, M., Yang, X., Siegel, G., A., Huffman, D.M., Schechter, C.B., Wright, W.E., Shay, J.W., Barzilai, Govindaraju, D.R., Suh, Y.,

Evolution in health and medicine Sackler um: genetic variation in human telomerase is associated with telomere length Ashkenazi centenarians. Proc. Natl. Acad. Sci. U. S. A.

,

–

Barrett, E.L., Richardson, D.S.,

Sex differences in telomeres and lifespan. Cell

,

–

Bellizzi, D., Rose, G., Cavalcante, P., Covello, G., Dato, S., De Rango, F., Greco, Maggiolini, M., Feraco, E., Mari, V., Franceschi, C., Passarino, G., De Benedictis,

A novel VNTR enhancer within the SIRT

gene, a human homologue SIR

, is associated with survival at oldest ages. Genomics

,

–

Bernardes de Jesus, B., Vera, E., Schneeberger, K., Tejera, A.M., Ayuso, E., Bosch, Blasco, M.A.,

Telomerase gene therapy in adult and old mice delays and increases longevity without increasing cancer. EMBO Mol. Med.

,

–

Blackburn, E.H.,

Telomeres and telomerase: the means to the end (Nobel ture). Angew. Chem. Int. Ed. Engl.

,

–

Bodnar, A.G., Ouellette, M., Frolkis, M., Holt, S.E., Chiu, C.P., Morin, G.B., Harley, Shay, J.W., Lichtsteiner, S., Wright, W.E.,

Extension of life-span by tion of telomerase into normal human cells. Science

,

–

Carpentier, C., Lejeune, J., Gros, F.,Everhard, S., Marie, Y., Kaloshi, G., Laigle-Donadey, Hoang-Xuan, K., Delattre, J.Y., Sanson, M.,

Association of telomerase

ERT polymorphism and malignant gliomas. J. Neurooncol.

,

–

Cawthon, R.M.,

Telomere length measurement by a novel monochrome plex quantitative PCR method. Nucleic Acids Res.

, e

Chan, S.R., Blackburn, E.H.,

Telomeres and telomerase. Philos. Trans. R. Soc. B Biol. Sci.

,

–

Chang, C.C., Yu, M.C., Bai, K.J., Chang, J.H., Lee, C.N., Fang, C.L., Liu, H.E.,