Extending healthy life span--from yeast to humans.
When the food intake of organisms such as yeast and rodents is reduced (dietary restriction), they live longer than organisms fed a normal diet. A similar effect is seen when the activity of nutrient-sensing pathways is reduced by mutations or chemical inhibitors. In rodents, both dietary restriction and decreased nutrient-sensing pathway activity can lower the incidence of age-related loss of function and disease, including tumors and neurodegeneration. Dietary restriction also increases life span and protects against diabetes, cancer, and cardiovascular disease in rhesus monkeys, and in humans it causes changes that protect against these age-related pathologies. Tumors and diabetes are also uncommon in humans with mutations in the growth hormone receptor, and natural genetic variants in nutrient-sensing pathways are associated with increased human life span. Dietary restriction and reduced activity of nutrient-sensing pathways may thus slow aging by similar mechanisms, which have been conserved during evolution. We discuss these findings and their potential application to prevention of age-related disease and promotion of healthy aging in humans, and the challenge of possible negative side effects.
Fontana
Luigi
L
Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St. Louis, MO 63110, USA. lfontana@dom.wustl.edu
Partridge
Linda
L
Longo
Valter D
VD
D000375:Aging; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology; D031204:Caloric Restriction; D004330:Drosophila / Q000235:genetics / Q000502:physiology; D004435:Eating; D000882:Haplorhini; D006801:Humans; D008136:Longevity; D051379:Mice; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction
Curr Biol. 2004 May 25;14(10):885-90
15186745
Aging Cell. 2009 Aug;8(4):346-52
19485964
Aging Cell. 2007 Feb;6(1):63-71
17266676
Cell Cycle. 2009 Apr 15;8(8):1256-70
19305133
Acta Paediatr Scand Suppl. 1991;377:115-7
1723834
BMC Dev Biol. 2008 May 05;8:49
18457595
Toxicol Pathol. 2009 Jan;37(1):47-51
19075044
Growth Horm IGF Res. 2007 Feb;17(1):54-7
17166755
PLoS Biol. 2007 Oct 2;5(10):e261
17914901
Genes Dev. 2006 Jan 15;20(2):174-84
16418483
Neurobiol Aging. 2005 Jul;26(7):995-1000
15748777
Science. 2009 Jul 10;325(5937):201-4
19590001
Aging Cell. 2008 Mar;7(2):199-206
18221413
JAMA. 2007 Mar 7;297(9):986-94
17341713
Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2325-30
18287083
Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3438-42
18316725
Mech Ageing Dev. 1996 Jul 31;89(1):21-43
8819104
Nature. 2009 Jul 16;460(7253):396-9
19553937
PLoS Genet. 2009 May;5(5):e1000486
19461873
J Gerontol A Biol Sci Med Sci. 2009 Nov;64(11):1114-25
19633237
Nature. 2009 Jul 16;460(7253):392-5
19587680
J Gerontol. 1993 Jan;48(1):B27-32
8418135
J Intern Med. 2008 Feb;263(2):179-91
18226095
Cell Metab. 2008 Aug;8(2):157-68
18599363
PLoS One. 2009 Jun 18;4(6):e5963
19536287
Science. 2009 May 29;324(5931):1196-8
19372390
Endocrinology. 2005 Sep;146(9):3718-23
15919742
PLoS Genet. 2009 May;5(5):e1000467
19424415
PLoS Genet. 2007 Apr 27;3(4):e57
17465680
Proc Biol Sci. 1996 Jun 22;263(1371):755-9
8763795
Science. 2000 Sep 22;289(5487):2126-8
11000115
PLoS One. 2008;3(11):e3721
19005568
Annu Rev Biochem. 2008;77:727-54
18373439
Age (Dordr). 2008 Sep;30(2-3):147-56
19424864
Science. 2001 Apr 13;292(5515):288-90
11292860
Trends Endocrinol Metab. 2009 Aug;20(6):259-64
19646896
PLoS Genet. 2008 Feb;4(2):e24
18282106
J Cell Biol. 1997 Jun 30;137(7):1581-8
9199172
Aging Cell. 2007 Oct;6(5):649-62
17711561
J Clin Endocrinol Metab. 2007 Dec;92(12):4664-70
17911170
Aging Cell. 2007 Oct;6(5):631-7
17874997
J Clin Endocrinol Metab. 2003 Jul;88(7):3299-304
12843179
Aging Cell. 2008 Oct;7(5):681-7
18843793
Proc Natl Acad Sci U S A. 2008 Jun 17;105(24):8215-20
18378900
Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6659-63
15096581
PLoS Genet. 2008 Jan;4(1):e13
18225956
Science. 2007 Feb 23;315(5815):1133-7
17272684
Nature. 2009 Dec 24;462(7276):1061-4
19956092
Cell. 2007 Jul 27;130(2):247-58
17662940
Aging Cell. 2008 Jun;7(3):394-404
18331616
J Gerontol A Biol Sci Med Sci. 2009 May;64(5):522-9
19228785
Aging Cell. 2009 Apr;8(2):113-27
19239417
J Gerontol A Biol Sci Med Sci. 2007 Oct;62(10):1071-81
17921418
Genome Biol. 2007;8(7):R132
17612391
PLoS Genet. 2007 May 25;3(5):e84
17530929
Nat Methods. 2008 Mar;5(3):214-215
18309307
Cell. 2005 Nov 18;123(4):655-67
16286010
Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):3105-10
15708981
Cell. 2008 Mar 21;132(6):1025-38
18358814
Cell. 2003 Nov 14;115(4):489-502
14622602
Mech Ageing Dev. 2008 Sep;129(9):528-33
18565572
Aging (Albany NY). 2009 Jan 28;1(1):131-45
20157595
Aging Cell. 2008 Mar;7(2):187-98
18241326