Cell size and growth rate are major determinants of replicative lifespan.
Yeast cells, like mammalian cells, enlarge steadily as they age. Unabated cell growth can promote cellular senescence; however, the significance of the relationship between size and cellular lifespan is not well understood. Herein, we report a genetic link between cell size, growth rate and lifespan. Mutations that increase cell size concomitantly increase growth rate and decrease lifespan. As a result, large cells grow, divide and age dramatically faster than small cells. Conversely, small cell mutants age slowly and are long-lived. Investigation of the mechanisms involved suggests that attainment of a maximal size modulates lifespan. Indeed, cumulative results revealed that life expectancy is size-dependent, and that the rate at which cells age is determined in large part by the amount of cell growth per generation.
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
Jingye
J
Yang
Huzefa
H
Dungrawala
Hui
H
Hua
Arkadi
A
Manukyan
Lesley
L
Abraham
Wesley
W
Lane
Holly
H
Mead
Jill
J
Wright
Brandt L
BL
Schneider
D002455:Cell Division / Q000502:physiology*; D049108:Cell Enlargement; D049109:Cell Proliferation; D048429:Cell Size; D016922:Cellular Senescence / Q000502:physiology*; D009154:Mutation / Q000502:physiology; D015003:Yeasts / Q000166:cytology* / Q000502:physiology*
Curr Opin Cell Biol. 2008 Dec;20(6):723-8
18848886
Annu Rev Microbiol. 1998;52:533-60
9891807
Exp Cell Res. 1967 Feb;45(2):336-50
6021926
Genetics. 2002 Jan;160(1):83-95
11805047
Mech Ageing Dev. 1981 Mar;15(3):251-67
7253715
Biogerontology. 2009 Aug;10(4):481-8
18985429
J Cell Physiol. 1990 May;143(2):222-5
2332448
Exp Gerontol. 1989;24(5-6):383-93
2632279
In Vitro. 1977 May;13(5):297-300
326658
Cell Cycle. 2009 Jun 15;8(12):1901-4
19471118
Oncogene. 1999 Aug 26;18(34):4808-18
10490814
Exp Cell Res. 1976 Dec;103(2):247-55
1001362
J Gerontol. 1990 Jan;45(1):B9-17
2404060
Science. 2005 Nov 18;310(5751):1193-6
16293764
Mech Ageing Dev. 1983 Oct;23(2):191-8
6656306
J Cell Physiol. 1989 Aug;140(2):288-94
2745563
Genetics. 2002 Sep;162(1):73-87
12242224
Nature. 2010 Mar 25;464(7288):513-9
20336133
Mech Ageing Dev. 2005 Apr;126(4):491-504
15722108
Acta Biochim Pol. 2006;53(4):747-51
17106513
J Cell Physiol. 1987 Jul;132(1):125-30
3597549
PLoS Biol. 2004 Sep;2(9):E296
15328540
J Bacteriol. 1993 May;175(10):3174-81
8491731
Exp Gerontol. 2007 Apr;42(4):275-86
17174052
Cell Cycle. 2008 Nov 1;7(21):3355-61
18948731
Aging (Albany NY). 2009 Dec 31;1(12):1008-16
20157583
Trends Biochem Sci. 1998 Apr;23(4):131-4
9584615
Acta Biochim Pol. 2006;53(4):833-5
17106512
Cell. 2008 Apr 18;133(2):292-302
18423200
Nature. 1959 Jun 20;183(4677):1751-2
13666896
J Cell Biol. 1994 Dec;127(6 Pt 2):1985-93
7806576
Methods Mol Biol. 2004;241:55-76
14970646
Aging (Albany NY). 2009 Apr 20;1(4):357-62
20157523
Mech Ageing Dev. 1976 Jan-Feb;5(1):45-56
1263608
Antonie Van Leeuwenhoek. 1985;51(1):1-10
3890734
Cell. 2004 Jun 25;117(7):899-913
15210111
Cell Cycle. 2009 Jun 15;8(12):1888-95
19471117
Cancer Res. 1999 Aug 1;59(15):3761-7
10446993
Cell Cycle. 2009 Jun 15;8(12):1896-900
19478560
Antonie Van Leeuwenhoek. 1966;32(1):94-8
5296610
Med Exp Int J Exp Med. 1969;19(6):313-20
5408801
Science. 1999 Aug 6;285(5429):901-6
10436161
Curr Biol. 2002 Dec 10;12(23):1992-2001
12477387
Proc Natl Acad Sci U S A. 1974 Jun;71(6):2231-5
4366757
Genes Dev. 2004 Oct 15;18(20):2491-505
15466158
Exp Cell Res. 1976 Mar 15;98(2):298-302
1253848
Curr Aging Sci. 2008 Dec;1(3):159-65
20021387
Mol Cell Biol. 2002 Nov;22(22):8056-66
12391171
Yeast. 1999 Oct;15(14):1511-8
10514568
Genes Dev. 2009 Jun 15;23(12):1408-22
19528319
Exp Cell Res. 1961 Dec;25:585-621
13905658
Science. 2002 Jul 19;297(5580):395-400
12089449