Converging pathways in lifespan regulation.
The processes that determine an organism's lifespan are complex and poorly understood. Yet single gene manipulations and environmental interventions can substantially delay age-related morbidity. In this review, we focus on the two most potent modulators of longevity: insulin/insulin-like growth factor 1 (IGF-1) signaling and dietary restriction. The remarkable molecular conservation of the components associated with insulin/IGF-1 signaling and dietary restriction allow us to understand longevity from a multi-species perspective. We summarize the most recent findings on insulin/IGF-1 signaling and examine the proteins and pathways that reveal a more genetic basis for dietary restriction. Although insulin/IGF-1 signaling and dietary restriction pathways are currently viewed as being independent, we suggest that these two pathways are more intricately connected than previously appreciated. We highlight that numerous interactions between these two pathways can occur at multiple levels. Ultimately, both the insulin/IGF-1 pathway and the pathway that mediates the effects of dietary restriction have evolved to respond to the nutritional status of an organism, which in turn affects its lifespan.
Narasimhan
Sri Devi
SD
Program in Gene Function and Expression, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
Yen
Kelvin
K
Tissenbaum
Heidi A
HA
D000818:Animals; D031204:Caloric Restriction; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008136:Longevity / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009812:Odorants; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D037761:Sirtuins / Q000378:metabolism; D013045:Species Specificity
D007328:Insulin; D017526:Receptor, IGF Type 1; D037761:Sirtuins
Oncogene. 2008 Apr 7;27(16):2276-88
18391970
BMC Dev Biol. 2008 May 05;8:49
18457595
Aging Cell. 2006 Dec;5(6):487-94
17081160
Genes Dev. 2001 Mar 15;15(6):672-86
11274053
PLoS Genet. 2009 Apr;5(4):e1000450
19360127
Aging Cell. 2006 Apr;5(2):119-26
16626391
J Gerontol A Biol Sci Med Sci. 2006 May;61(5):444-60
16720740
Aging Cell. 2008 Mar;7(2):199-206
18221413
Science. 2005 Nov 18;310(5751):1193-6
16293764
Annu Rev Genet. 2006;40:159-85
16771627
Curr Biol. 2004 May 25;14(10):885-90
15186745
Science. 2003 Sep 5;301(5638):1387-91
12958363
Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2325-30
18287083
Nature. 2009 Feb 5;457(7230):726-30
19079239
Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1768-73
16446459
Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3438-42
18316725
Science. 2002 Apr 12;296(5566):319
11951037
J Biol Chem. 2006 Sep 15;281(37):27643-52
16847060
J Am Aging Assoc. 2000 Apr;23(2):55-73
23604840
PLoS Genet. 2007 Apr 6;3(4):e56
17411345
Nat Genet. 2008 Mar;40(3):356-61
18246068
Physiol Behav. 1985 Oct;35(4):603-6
3906712
J Biol Chem. 2005 Dec 9;280(49):40406-16
16221682
J Biol Chem. 2007 Jul 20;282(29):21176-86
17510058
Exp Gerontol. 2008 Dec;43(12):1058-60
18790043
Nature. 1999 Dec 16;402(6763):804-9
10617200
Mol Cell. 2008 Jun 20;30(6):701-11
18570873
Curr Biol. 2008 Sep 23;18(18):1355-64
18804378
Mech Ageing Dev. 2004 Jun;125(6):455-64
15178135
Mol Cell. 2008 Apr 25;30(2):214-26
18439900
Mol Microbiol. 2005 Aug;57(4):988-1007
16091039
Genetics. 1998 Sep;150(1):129-55
9725835
Am J Physiol Endocrinol Metab. 2003 Nov;285(5):E1064-71
14534077
Physiol Behav. 2006 Aug 30;89(1):10-4
16712883
Curr Biol. 2007 Oct 9;17(19):1646-56
17900900
Development. 2004 Aug;131(16):3897-906
15253933
Science. 2004 Jul 16;305(5682):390-2
15205477
Cell. 2005 Feb 25;120(4):449-60
15734678
Aging Cell. 2007 Feb;6(1):95-110
17266679
PLoS Genet. 2007 Sep;3(9):1565-71
17907808
Nat Genet. 2003 Jan;33(1):40-8
12447374
Cell. 2006 Mar 10;124(5):1039-53
16530049
Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13091-6
9789046
Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2700-5
19196970
Exp Gerontol. 2004 Jun;39(6):947-9
15217699
Annu Rev Biochem. 2008;77:727-54
18373439
PLoS One. 2007 Nov 28;2(11):e1240
18043747
Genome Biol. 2007;8(12):R262
18067683
Cancer Cell. 2007 Jul;12(1):9-22
17613433
Nature. 2003 Dec 11;426(6967):620
14668850
Autophagy. 2007 Mar-Apr;3(2):93-5
17204841
Genetics. 2002 Jul;161(3):1101-12
12136014
Science. 2007 Aug 3;317(5838):660-3
17673661
Genes Dev. 2009 Feb 15;23(4):496-511
19240135
Science. 2001 Apr 6;292(5514):107-10
11292875
Cell Metab. 2008 Jul;8(1):38-48
18590691
PLoS Genet. 2008 Feb;4(2):e24
18282106
J Biol Chem. 2007 Oct 12;282(41):30107-19
17711846
Science. 2007 Apr 6;316(5821):112-5
17412960
Am J Physiol Heart Circ Physiol. 2008 Dec;295(6):H2348-55
18931029
PLoS Biol. 2008 Sep 30;6(9):e233
18828672
Science. 2002 Dec 20;298(5602):2398-401
12471266
Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):13987-92
18765803
Am J Physiol Endocrinol Metab. 2004 Nov;287(5):E1032-7
15251868
Cell Metab. 2007 Oct;6(4):280-93
17908557
Exp Gerontol. 2006 Oct;41(10):894-903
16919905
PLoS One. 2008 Mar 12;3(3):e1759
18335035
Science. 2005 Dec 9;310(5754):1641
16339438
Genes Dev. 2003 Apr 1;17(7):844-58
12654727
J Biol Chem. 2008 Sep 19;283(38):26217-27
18635541
PLoS One. 2009;4(2):e4535
19229346
Biogerontology. 2006 Jun;7(3):157-60
16628489
Cell. 2003 Nov 26;115(5):577-90
14651849
Genes Dev. 2003 Apr 1;17(7):826-31
12654724
Science. 2007 Feb 23;315(5815):1133-7
17272684
Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13289-94
16150727
J Biol Chem. 2004 Aug 27;279(35):36739-45
15155758
Oncogene. 2008 Apr 7;27(16):2345-50
18391976
Nature. 2007 May 31;447(7144):550-5
17476212
Dev Cell. 2002 Jan;2(1):9-19
11782310
Aging Cell. 2006 Dec;5(6):515-24
17096674
EMBO J. 1996 Dec 2;15(23):6541-51
8978681
Nature. 2007 May 31;447(7144):545-9
17538612
PLoS Biol. 2009 Mar 3;7(3):e60
19260765
Biochem J. 2009 Feb 15;418(1):1-12
19159343
Aging Cell. 2009 Apr;8(2):113-27
19239417
Genes Dev. 2008 Jul 1;22(13):1753-7
18550784
Interdiscip Top Gerontol. 2007;35:69-82
17063033
Nat Rev Mol Cell Biol. 2007 Sep;8(9):681-91
17684529
Exp Gerontol. 2003 Sep;38(9):947-54
12954481
Science. 1997 Aug 15;277(5328):942-6
9252323
Cell. 2009 Mar 6;136(5):939-51
19249087
Science. 1996 May 17;272(5264):1010-3
8638122
Biol Chem. 2008 Mar;389(3):279-83
18208360
Biochem J. 2008 Dec 15;416(3):375-85
18925875
Nature. 2004 Jun 3;429(6991):562-6
15175753
Curr Opin Cell Biol. 2008 Apr;20(2):126-36
18394876
Biochem Biophys Res Commun. 2004 Apr 16;316(4):1196-201
15044112
Dev Cell. 2008 Jan;14(1):76-85
18194654
EMBO J. 2005 Mar 9;24(5):1021-32
15692560
BMC Biol. 2006 Feb 03;4:1
16457721
Nature. 2004 Sep 9;431(7005):200-5
15306821
Annu Rev Nutr. 2008;28:295-311
18429698
Dev Cell. 2001 Nov;1(5):633-44
11709184
Biochem J. 2004 Jun 1;380(Pt 2):297-309
15005655
Cell. 2008 Mar 21;132(6):1025-38
18358814
Mutat Res. 2008 Jul-Aug;659(1-2):31-9
18164232
Mol Cell Endocrinol. 2009 Feb 5;299(1):51-7
19059305
Dev Cell. 2004 Apr;6(4):577-88
15068796
Res Vet Sci. 2007 Apr;82(2):208-14
16919689
Exp Gerontol. 2006 Oct;41(10):928-34
16839734
J Am Soc Nephrol. 2006 Aug;17(8):2236-44
16807405