Editors' ChoiceAging

Methylation and Methuselah?

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Science Signaling  18 Jun 2013:
Vol. 6, Issue 280, pp. ec139
DOI: 10.1126/scisignal.2004418

Hutchinson-Gilford progeria syndrome (HGPS) and other prelamin A–associated progeroid disorders, which are premature aging conditions, arise when farnesylated and methylated forms of prelamin A accumulate at the nuclear envelope. Ibrahim et al. (see the Perspective by Johnson) show that reducing the activity of the isoprenylcysteine carboxyl methyltransferase (ICMT) mislocalizes prelamin A, triggers prelamin A–dependent AKT–mammalian target of rapamycin signaling, and eliminates disease phenotypes in 30-week-old progeria model mice. Reduced ICMT expression increased the proliferation and delayed the premature senescence of progeria model mouse fibroblasts and cells from children with HGPS.

M. X. Ibrahim, V. I. Sayin, M. K. Akula, M. Liu, L. G. Fong, S. G. Young, M. O. Bergo, Targeting isoprenylcysteine methylation ameliorates disease in a mouse model of progeria. Science 340, 1330–1333 (2013). [Abstract] [Full Text]

T. E. Johnson, Rapid aging rescue? Science 340, 1299–1300 (2013). [Abstract] [Full Text]

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