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PMID: 20404395 Published · ppublish English Journal Article

Why human lifespan is rapidly increasing: solving "longevity riddle" with "revealed-slow-aging" hypothesis.

Aging ·Vol. 2 ·No. 4 ·2010-04-00 ·Pages 177-82

Blagosklonny MV

Abstract

Healthy life span is rapidly increasing and human aging seems to be postponed. As recently exclaimed in Nature, these findings are so perplexing that they can be dubbed the 'longevity riddle'. To explain current increase in longevity, I discuss that certain genetic variants such as hyper-active mTOR (mTarget of Rapamycin) may increase survival early in life at the expense of accelerated aging. In other words, robustness and fast aging may be associated and slow-aging individuals died prematurely in the past. Therefore, until recently, mostly fast-aging individuals managed to survive into old age. The progress of civilization (especially 60 years ago) allowed slow-aging individuals to survive until old age, emerging as healthy centenarians now. I discuss why slow aging is manifested as postponed (healthy) aging, why the rate of deterioration is independent from aging and also entertain hypothetical use of rapamycin in different eras as well as the future of human longevity.

MeSH Terms
Aged Aging/genetics,physiology Humans Intracellular Signaling Peptides and Proteins/genetics,physiology Longevity/genetics,physiology Models, Biological Protein Serine-Threonine Kinases/genetics,physiology Signal Transduction TOR Serine-Threonine Kinases
Chemicals
Intracellular Signaling Peptides and Proteins MTOR protein, human Protein Serine-Threonine Kinases TOR Serine-Threonine Kinases
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Blagosklonny Mikhail V
Department of Cell Stress Biology, Roswell Park Cancer Institute, BLSC, L3-312, Buffalo, NY 14263, USA. [email protected]
References (30)
30 references, click to expand
  1. Ageing populations: the challenges ahead.
    Lancet. 2009 Oct 3;374(9696):1196-208 PMID: 19801098
  2. Rapamycin attenuates atherosclerotic plaque progression in apolipoprotein E knockout mice: inhibitory effect on monocyte chemotaxis.
    J Cardiovasc Pharmacol. 2005 Oct;46(4):481-6 PMID: 16160601
  3. mTOR's role in ageing: protein synthesis or autophagy?
    Aging (Albany NY). 2009 Jul 20;1(7):586-97 PMID: 20157541
  4. An anti-aging drug today: from senescence-promoting genes to anti-aging pill.
    Drug Discov Today. 2007 Mar;12(5-6):218-24 PMID: 17331886
  5. Oral rapamycin attenuates atherosclerosis without affecting the arterial responsiveness of resistance vessels in apolipoprotein E-deficient mice.
    Braz J Med Biol Res. 2009 Dec;42(12):1191-5 PMID: 19893993
  6. Everolimus suppresses cancellous bone loss, bone resorption, and cathepsin K expression by osteoclasts.
    Bone. 2004 Nov;35(5):1144-56 PMID: 15542040
  7. Aging and immortality: quasi-programmed senescence and its pharmacologic inhibition.
    Cell Cycle. 2006 Sep;5(18):2087-102 PMID: 17012837
  8. Infection, inflammation, height, and longevity.
    Proc Natl Acad Sci U S A. 2006 Jan 10;103(2):498-503 PMID: 16387863
  9. Demography. Broken limits to life expectancy.
    Science. 2002 May 10;296(5570):1029-31 PMID: 12004104
  10. Aging-suppressants: cellular senescence (hyperactivation) and its pharmacologic deceleration.
    Cell Cycle. 2009 Jun 15;8(12):1883-7 PMID: 19448395
  11. Increase of maximum life-span in Sweden, 1861-1999.
    Science. 2000 Sep 29;289(5488):2366-8 PMID: 11009426
  12. Low-dose oral sirolimus reduces atherogenesis, vascular inflammation and modulates plaque composition in mice lacking the LDL receptor.
    Br J Pharmacol. 2009 Mar;156(5):774-85 PMID: 19220291
  13. TOR signaling in growth and metabolism.
    Cell. 2006 Feb 10;124(3):471-84 PMID: 16469695
  14. Aging: ROS or TOR.
    Cell Cycle. 2008 Nov 1;7(21):3344-54 PMID: 18971624
  15. Rapamycin attenuates atherosclerosis induced by dietary cholesterol in apolipoprotein-deficient mice through a p27 Kip1 -independent pathway.
    Atherosclerosis. 2004 Jan;172(1):31-8 PMID: 14709354
  16. Pharmacological inhibition of phosphoinositide 3 and TOR kinases improves survival of Drosophila melanogaster.
    Rejuvenation Res. 2010 Apr-Jun;13(2-3):246-7 PMID: 20017609
  17. mTOR regulates memory CD8 T-cell differentiation.
    Nature. 2009 Jul 2;460(7251):108-12 PMID: 19543266
  18. Prevention of atherosclerosis by the mTOR inhibitor everolimus in LDLR-/- mice despite severe hypercholesterolemia.
    Atherosclerosis. 2008 May;198(1):39-48 PMID: 17980369
  19. Validation of anti-aging drugs by treating age-related diseases.
    Aging (Albany NY). 2009 Mar 28;1(3):281-8 PMID: 20157517
  20. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice.
    Nature. 2009 Jul 16;460(7253):392-5 PMID: 19587680
  21. TOR-driven aging: speeding car without brakes.
    Cell Cycle. 2009 Dec 15;8(24):4055-9 PMID: 19923900
  22. Growth stimulation leads to cellular senescence when the cell cycle is blocked.
    Cell Cycle. 2008 Nov 1;7(21):3355-61 PMID: 18948731
  23. Inflammatory exposure and historical changes in human life-spans.
    Science. 2004 Sep 17;305(5691):1736-9 PMID: 15375259
  24. Upstream and downstream of mTOR.
    Genes Dev. 2004 Aug 15;18(16):1926-45 PMID: 15314020
  25. Growth and aging: a common molecular mechanism.
    Aging (Albany NY). 2009 Apr 20;1(4):357-62 PMID: 20157523
  26. Protective effect of the immunosuppressant sirolimus against aortic atherosclerosis in apo E-deficient mice.
    Am J Transplant. 2003 May;3(5):562-9 PMID: 12752312
  27. Prevention of cancer by inhibiting aging.
    Cancer Biol Ther. 2008 Oct;7(10):1520-4 PMID: 18769112
  28. Rapamycin extends maximal lifespan in cancer-prone mice.
    Am J Pathol. 2010 May;176(5):2092-7 PMID: 20363920
  29. Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster.
    Cell Metab. 2010 Jan;11(1):35-46 PMID: 20074526
  30. Biodemography of human ageing.
    Nature. 2010 Mar 25;464(7288):536-42 PMID: 20336136
Article Info
Journal
Aging
Abbr.
Aging (Albany NY)
ISSN
1945-4589
DOI
10.18632/aging.100139
Email
[email protected]
Published
2010-04-00
Epub
2010-00-18
Pages
177-82
Language
English
Region
United States
NLM ID
101508617
PMCID
PMC2881507
Subset
IM
External Links
PubMed source DOI: 10.18632/aging.100139 PMC Full Text View journal details
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