title: The effects of aging on apoptosis following myocardial infarction.
abstract: BACKGROUND
  Aging is associated with higher incidence of heart failure and death following myocardial infarction (MI). The molecular and cellular changes that lead to these worse outcomes are not known.
  
  
  RESULTS
  Young and aging mice underwent induction of MI by LAD ligation. There was a significant increase in mortality in the aging mice. Neither the young nor aging hearts after MI had inducible ventricular tachycardia. Cardiomyocyte apoptosis increases early after MI in young and aging mice, but to a much greater degree in the aging mice. Caspase inhibition with Ac-DEVD-CHO resulted in a 61% reduction in activated caspase-3 and an 84% reduction in apoptosis in cardiomyocytes in young mice (P < 0.05), but not in aging mice. Gene pathway profiling demonstrated activation of both the caspase and Map3k1/Mapk10 pathways in aging mice following MI, which may contribute to their resistance to caspase inhibition.
  
  
  CONCLUSIONS
  Aging hearts activate distinct apoptotic pathways have more cardiomyocyte apoptosis and are resistant to antiapoptotic therapies following MI. Novel or combination approaches may be required to improve outcomes in aging patients following MI.
authors.affiliation: Department of Medicine, Division of Cardiology, University of California San Francisco, San Francisco, CA, USA; Edyth and Eli Broad Center for Regenerative Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Boyle
authors.forename: Joy
authors.initials: J
authors.lastname: Hwang
authors.forename: Jianqin
authors.initials: J
authors.lastname: Ye
authors.forename: Henry
authors.initials: H
authors.lastname: Shih
authors.forename: Kristine
authors.initials: K
authors.lastname: Jun
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Fang
authors.forename: Richard
authors.initials: R
authors.lastname: Sievers
authors.forename: Yerem
authors.initials: Y
authors.lastname: Yeghiazarians
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Lee
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000401:mortality / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology
chemical_list: D053148:Caspase 3
keywords: Aging; Apoptosis; Cardiomyocyte; Heart failure; Ventricular remodeling