Life extension by diet restriction and N-acetyl-L-cysteine in genetically heterogeneous mice.
We used a heterogeneous stock of mice-UM-HET3, the first generation offspring of CByB6F1/J and C3D2F1/J parents-to test effects of six antiaging treatments on life span. In the first report of diet restriction in a structured, segregating heterogeneous population, we observed essentially the same increases in mean and maximum life span as found in CByB6F1/J hybrid positive controls. We also report results of treatment with N-acetyl-L-cysteine started at 7 months, and aspirin, nitroflurbiprofen, 4-hydroxy phenyl N-tert-butyl nitrone, and nordihydroguaiaretic acid, all started at 16-18 months. Only male UM-HET3 mice receiving N-acetyl-L-cysteine had significantly increased life span, and this may have been due to treatment-related inadvertent diet restriction. The other agents had no significant effects on life span. The use of UM-HET3 mice helps assure that these results are not the result of unresponsiveness of a single genotype but that they more broadly represent laboratory mice.
Flurkey
Kevin
K
The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
Astle
Clinton M
CM
Harrison
David E
DE
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D003433:Crosses, Genetic; D004032:Diet; D005260:Female; D005480:Flurbiprofen / Q000031:analogs & derivatives / Q000494:pharmacology; D007097:Imines / Q000494:pharmacology; D008017:Life Expectancy; D008136:Longevity / Q000187:drug effects; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D010636:Phenols / Q000494:pharmacology; D012737:Sex Factors
C554675:4-hydroxyphenyl tert-butylnitrone; D007097:Imines; D010636:Phenols; C095631:nitroflurbiprofen; D005480:Flurbiprofen; D009637:Masoprocol; D001241:Aspirin; D000111:Acetylcysteine
Mech Ageing Dev. 2004 Sep;125(9):629-32
15491681
Cardiologia. 1999 Jul;44(7):633-7
10476588
J Nutr. 1987 Feb;117(2):376-82
3559752
Mech Ageing Dev. 2002 Jan;123(2-3):131-44
11718807
Nature. 2009 Jul 16;460(7253):392-5
19587680
Scand J Gastroenterol. 2001 Aug;36(8):811-6
11495075
Aging Cell. 2007 Aug;6(4):565-75
17578509
Lupus. 2001;10(4):258-65
11341102
J Gerontol. 1991 May;46(3):B87-8
2030267
J Neuroimmunol. 2004 May;150(1-2):10-9
15081244
Proc Natl Acad Sci U S A. 1976 Apr;73(4):1279-83
1063408
Genetics. 1963 Feb;48:205-16
13974616
Mech Ageing Dev. 2005 Sep;126(9):913-22
15885745
J Gerontol A Biol Sci Med Sci. 1999 Aug;54(8):B358-60
10496542
Aging Cell. 2006 Dec;5(6):441-9
17054664
Mech Ageing Dev. 1990 Jul;55(1):69-87
2402168
Aging Cell. 2010 Feb;9(1):92-5
19878144
N Engl J Med. 2005 Nov 24;353(21):2229-42
16306520
Kidney Int. 2005 Nov;68(5):2208-17
16221220
Neurosci Lett. 1996 Mar 1;205(3):181-4
8852588
Exp Gerontol. 1997 Jan-Apr;32(1-2):55-63
9088902
Pharmacology. 1993;46(3):121-9
8441760
Mech Ageing Dev. 2004 May;125(5):381-90
15130756
Biosci Biotechnol Biochem. 1998 Apr;62(4):792-4
9614711
Blood. 1997 Aug 1;90(3):1124-32
9242544
J Immunol. 2002 Aug 1;169(3):1619-25
12133992
J Gerontol A Biol Sci Med Sci. 1999 Nov;54(11):B492-501
10619312
Exp Gerontol. 2010 Sep;45(9):691-701
20452416
J Gerontol. 1994 Jan;49(1):B1-11
8282970
Fed Proc. 1947;6(1):318
20343665
J Gerontol. 1965 Jan;20:69-71
14246534
Altern Med Rev. 1998 Apr;3(2):114-27
9577247
Cell Mol Life Sci. 2003 Jan;60(1):6-20
12613655
Aging Cell. 2008 Oct;7(5):641-50
18631321
FASEB J. 2003 Apr;17(6):690-2
12586746