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REPORTS
Quantitation of the distribution of HP1 and Tri- the prolonged presence of D50 lamin A in the 9. Materials and methods are available as supporting
Me-K9H3 confirmed the restoration of amounts nucleus. Aged cells might be more sensitized to material on Science Online.
10. U. Herbig, M. Ferreira, L. Condel, D. Carey, J. M. Sedivy,
similar to those seen in cells from young in- the presence of the aberrant lamin A isoforms Science 311, 1257 (2006); published online 2 February
dividuals at similar passages (Fig. 4, B and C) and less able to neutralize the negative effects of 2006 (10.1126/science.1122446).
(P G 0.001). The reversibility of nuclear defects D50 lamin A, possibly due to the existence of a 11. O. A. Sedelnikova et al., Nat. Cell Biol. 6, 168 (2004).
upon blocking of the cryptic splice site in p53-dependent checkpoint, which senses struc- 12. I. Varela et al., Nature 437, 564 (2005).
13. S. G. Young, L. G. Fong, S. Michaelis, J. Lipid Res. 46,
LMNA directly demonstrates that lamin A is tural abnormalities of the nuclear lamina and 2531 (2005).
causal in generating the age-related nuclear de- links those to the activation of the senescence 14. S. H. Yang et al., Proc. Natl. Acad. Sci. U.S.A. 102,
fects. A smaller, but statistically significant, program (12). Given our finding that several 10291 (2005).
effect was also seen in cells from young indi- nuclear defects in aged cells are reversible upon 15. B. M. Machiels et al., J. Biol. Chem. 271, 9249
(1996).
viduals at later passages, further supporting a inhibition of the aberrant splicing event in 16. We thank D. Donato for help with statistical analysis,
correlation between age and lamin Adependent LMNA, it will be interesting to determine C. Baker for design of specific primer pairs, M. Sinensky
nuclear abnormalities (Fig. 4, B and C). whether other cellular features of aging respond for advice on metabolic labeling of farnesylated lamin A,
Organismal aging has been linked to activa- to such treatment and whether organismal aging and K. Wilson and T. Jenuwein for providing reagents.
Fluorescence imaging was performed at the NCI Fluo-
tion of p53-dependent signaling pathways and can be modulated by interference with lamin A.
rescence Imaging Facility. This research was supported by
initiation of the senescence program in a pre- the Intramural Research Program of the NIH, NCI, Center
mature aging mouse model (12). To test whether References and Notes for Cancer Research.
lamin A plays a role in the activation of p53- 1. C. J. Hutchison, Nat. Rev. Mol. Cell Biol. 3, 848 (2002).
2. A. De Sandre-Giovannoli et al., Science 300, 2055
dependent signaling pathways, we probed the Supporting Online Material