PMID: 11909679Mar 23, 2002Paper

The reserve-capacity hypothesis: evolutionary origins and modern implications of the trade-off between tumor-suppression and tissue-repair

Experimental Gerontology
Bret S Weinstein, Deborah Ciszek

Abstract

Antagonistic pleiotropy, the evolutionary theory of senescence, posits that age related somatic decline is the inevitable late-life by-product of adaptations that increase fitness in early life. That concept, coupled with recent findings in oncology and gerontology, provides the foundation for an integrative theory of vertebrate senescence that reconciles aspects of the 'accumulated damage' 'metabolic rate', and 'oxidative stress' models. We hypothesize that (1) in vertebrates, a telomeric fail-safe inhibits tumor formation by limiting cellular proliferation. (2) The same system results in the progressive degradation of tissue function with age. (3) These patterns are manifestations of an evolved antagonistic pleiotropy in which extrinsic causes of mortality favor a species-optimal balance between tumor suppression and tissue repair. (4) With that trade-off as a fundamental constraint, selection adjusts telomere lengths--longer telomeres increasing the capacity for repair, shorter telomeres increasing tumor resistance. (5) In environments where extrinsically induced mortality is frequent, selection against senescence is comparatively weak as few individuals live long enough to suffer a substantial phenotypic decline. The weaker...Continue Reading

References

Nov 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·R C AllsoppC B Harley
Jan 1, 1992·Annual Review of Biochemistry·E H Blackburn
Sep 27, 1990·Nature·D Kipling, H J Cooke
May 31, 1990·Nature·C B HarleyC W Greider
Sep 1, 1969·The British Journal of Dermatology·M M Black
Sep 1, 1966·Journal of Theoretical Biology·W D Hamilton
Aug 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·D Röhme
Nov 21, 1995·Proceedings of the National Academy of Sciences of the United States of America·E Chang, C B Harley
Dec 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·R G FaragherS Shall
Mar 7, 1996·Nature·K H CampbellI Wilmut
Nov 1, 1996·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Y LiN Wolf
Nov 14, 1997·Molecular Human Reproduction·G A Ulaner, L C Giudice
Feb 21, 1998·Proceedings of the National Academy of Sciences of the United States of America·C W Greider
Feb 7, 1998·Science·T de Lange
Sep 2, 1998·Proceedings of the National Academy of Sciences of the United States of America·V J CristofaloJ C Beck
May 25, 1999·Cell·C W Greider
Mar 18, 2000·Proceedings of the Society for Experimental Biology and Medicine·I Savre-TrainS E Holt
Mar 31, 2000·Science·D H LyP G Schultz
Jun 24, 2000·Nature·N PaulyC Mazars
Nov 10, 2000·Nucleic Acids Research·M T Hemann, C W Greider
Apr 11, 2001·Experimental Gerontology·J Campisi
Jan 10, 2002·Nature·Stuart D TynerLawrence A Donehower
Dec 1, 1961·Experimental Cell Research·L HAYFLICK, P S MOORHEAD

❮ Previous
Next ❯

Citations

Nov 17, 2006·Nature Reviews. Cancer·Lauren M F MerloCarlo C Maley
Aug 19, 2011·Nature Reviews. Cancer·Franziska MichorJonathan Widom
Apr 5, 2012·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Kaare ChristensenAxel Skytthe
Dec 20, 2005·Journal of Epidemiology and Community Health·Johan P Mackenbach
Dec 16, 2003·American Journal of Veterinary Research·Tom P McKevittDavid J Argyle
Jul 13, 2004·Annals of the New York Academy of Sciences·Mark F HaussmannCarol M Vleck
Jun 10, 2006·Biological Reviews of the Cambridge Philosophical Society·Bernard J Crespi, Kyle Summers
Feb 15, 2011·American Journal of Human Biology : the Official Journal of the Human Biology Council·Dan T A Eisenberg
May 28, 2015·Neuro-oncology·Kyle M WalshMargaret R Wrensch
Aug 25, 2004·Medical Hypotheses·George E Davis, Walter E Lowell
May 17, 2006·Trends in Ecology & Evolution·Bernard Crespi, Kyle Summers
Apr 29, 2014·International Journal of Cancer. Journal International Du Cancer·Fatemeh Saberi HosnijehRoel Vermeulen
Jun 10, 2015·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·David Haig
Jun 10, 2015·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Joel S BrownRobert A Gatenby
May 20, 2015·Human Genetics·Jennifer H BarrettKaren A Pooley
Nov 8, 2016·Ageing Research Reviews·Antonio Currais
Jan 17, 2017·Ecology Letters·Michael E Hochberg, Robert J Noble
May 2, 2003·Nature Reviews. Cancer·Judith Campisi
Feb 16, 2007·Nature Reviews. Cancer·Mel Greaves
Sep 16, 2020·Seminars in Immunopathology·T FulopJ M Witkowski

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Medical Hypotheses
K SummersM Farwell
European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (ECP)
A A WadeeH H Vorster
The Veterinary Clinics of North America. Exotic Animal Practice
John E Cooper
Proceedings. Biological Sciences
Kyle Summers, Bernard Crespi
© 2022 Meta ULC. All rights reserved