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Cited by 376

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

Combined treatment with statins and aminobisphosphonates extends longevity in a mouse model of human premature aging

Varela, Ignacio, Pereira, Sandrine, Ugalde, Alejandro P, Navarro, Claire L, Suárez, María F, Cau, Pierre, Cadiñanos, Juan, Osorio, Fernando G, Foray, Nicolas, Cobo, Juan, de Carlos, Félix, Lévy, Nicolas, Freije, José M P, López-Otín, Carlos·2008·Nature Medicine
DOI 10.1038/nm1786
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Abstract

Several human progerias, including Hutchinson-Gilford progeria syndrome (HGPS), are caused by the accumulation at the nuclear envelope of farnesylated forms of truncated prelamin A, a protein that is also altered during normal aging. Previous studies in cells from individuals with HGPS have shown that farnesyltransferase inhibitors (FTIs) improve nuclear abnormalities associated with prelamin A accumulation, suggesting that these compounds could represent a therapeutic approach for this devastating progeroid syndrome. We show herein that both prelamin A and its truncated form progerin/LADelta50 undergo alternative prenylation by geranylgeranyltransferase in the setting of farnesyltransferase inhibition, which could explain the low efficiency of FTIs in ameliorating the phenotypes of progeroid mouse models. We also show that a combination of statins and aminobisphosphonates efficiently inhibits both farnesylation and geranylgeranylation of progerin and prelamin A and markedly improves the aging-like phenotypes of mice deficient in the metalloproteinase Zmpste24, including growth retardation, loss of weight, lipodystrophy, hair loss and bone defects. Likewise, the longevity of these mice is substantially extended. These findings open a new therapeutic approach for human progeroid syndromes associated with nuclear-envelope abnormalities.

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Crossref · 10.1038/nm1786

Cites

3 of 3 references verified0 citation errors · 0 not checkable

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Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Decreasing prelamin A or progerin levels delays the onset of progeroid features and extends lifespan in mouse models of HGPS.

    “The causal relevance of nuclear lamina abnormalities in premature aging has been supported by the observation that decreasing prelamin A or progerin levels delays the onset of progeroid features and extends lifespan in mouse models of HGPS.”

    From The Hallmarks of Aging (2013) · cites this paper as Varela et al., 2008

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 27

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  2. Young, S.G., Meta, M., Yang, S.H. & Fong, L.G. Prelamin A farnesylation and progeroid syndromes. J. Biol. Chem. 281, 39741–39745 (2006). · DOI
  3. Kipling, D., Davis, T., Ostler, E.L. & Faragher, R.G. What can progeroid syndromes tell us about human aging? Science 305, 1426–1431 (2004). · DOI
  4. Hennekam, R.C. Hutchinson-Gilford progeria syndrome: review of the phenotype. Am. J. Med. Genet. A. 140, 2603–2624 (2006). · DOI
  5. Pendás, A.M. et al. Defective prelamin A processing and muscular and adipocyte alterations in Zmpste24 metalloproteinase–deficient mice. Nat. Genet. 31, 94–99 (2002). · DOI · Paper page
  6. Ramirez, C.L., Cadinanos, J., Varela, I., Freije, J.M. & López-Otín, C. Human progeroid syndromes, aging and cancer: new genetic and epigenetic insights into old questions. Cell. Mol. Life Sci. 64, 155–170 (2007). · DOI
  7. Liu, Y., Rusinol, A., Sinensky, M., Wang, Y. & Zou, Y. DNA damage responses in progeroid syndromes arise from defective maturation of prelamin A. J. Cell Sci. 119, 4644–4649 (2006). · DOI · Paper page
  8. Espada, J. et al. Nuclear envelope defects cause stem cell dysfunction in premature-aging mice. J. Cell Biol. 181, 27–35 (2008). · DOI · Paper page
  9. Cadiñanos, J., Varela, I., López-Otín, C. & Freije, J.M. From immature lamin to premature aging: molecular pathways and therapeutic opportunities. Cell Cycle 4, 1732–1735 (2005). · DOI
  10. Toth, J.I. et al. Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes. Proc. Natl. Acad. Sci. USA 102, 12873–12878 (2005). · DOI
  11. Capell, B.C. et al. Inhibiting farnesylation of progerin prevents the characteristic nuclear blebbing of Hutchinson-Gilford progeria syndrome. Proc. Natl. Acad. Sci. USA 102, 12879–12884 (2005). · DOI
  12. Mallampalli, M.P., Huyer, G., Bendale, P., Gelb, M.H. & Michaelis, S. Inhibiting farnesylation reverses the nuclear morphology defect in a HeLa cell model for Hutchinson-Gilford progeria syndrome. Proc. Natl. Acad. Sci. USA 102, 14416–14421 (2005). · DOI
  13. Glynn, M.W. & Glover, T.W. Incomplete processing of mutant lamin A in Hutchinson-Gilford progeria leads to nuclear abnormalities, which are reversed by farnesyltransferase inhibition. Hum. Mol. Genet. 14, 2959–2969 (2005). · DOI
  14. Fong, L.G. et al. A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria. Science 311, 1621–1623 (2006). · DOI
  15. Yang, S.H. et al. A farnesyltransferase inhibitor improves disease phenotypes in mice with a Hutchinson-Gilford progeria syndrome mutation. J. Clin. Invest. 116, 2115–2121 (2006). · DOI · Paper page
  16. Whyte, D.B. et al. K- and N-Ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors. J. Biol. Chem. 272, 14459–14464 (1997). · DOI · Paper page
  17. Rusinol, A.E. & Sinensky, M.S. Farnesylated lamins, progeroid syndromes and farnesyl transferase inhibitors. J. Cell Sci. 119, 3265–3272 (2006). · DOI
  18. Konstantinopoulos, P.A. & Papavassiliou, A.G. Multilevel modulation of the mevalonate and protein-prenylation circuitries as a novel strategy for anticancer therapy. Trends Pharmacol. Sci. 28, 6–13 (2007). · DOI
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  22. Demierre, M.F., Higgins, P.D., Gruber, S.B., Hawk, E. & Lippman, S.M. Statins and cancer prevention. Nat. Rev. Cancer 5, 930–942 (2005). · DOI
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Metadata

Authors
Varela, I., Pereira, S., Ugalde, A. P., Navarro, C. L., Suárez, M. F., Cau, P., Cadiñanos, J., Osorio, F. G., Foray, N., Cobo, J., de Carlos, F., Lévy, N., Freije, J. M. P., & López-Otín, C.
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2008-06-29
Volume
14
Issue
7
Pages
767-772
ISSN
  • 1078-8956
  • 1546-170X
DOI
10.1038/nm1786
Cited by
376
References
3
Language
en
Licence
www.springer.com/tdm (tdm)

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