FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2007509288> ?p ?o ?g. }

• W2007509288 endingPage "627" @default.
• W2007509288 startingPage "615" @default.
• W2007509288 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 the selection against senescence, the further the optimal balance point moves toward shorter telomeres and increased tumor suppression. The stronger the selection against senescence, the farther the optimal balance point moves toward longer telomeres, increasing the capacity for tissue repair, slowing senescence and elevating tumor risks. (6) In iteroparous organisms selection tends to co-ordinate rates of senescence between tissues, such that no one organ generally limits life-span. A subsidiary hypothesis argues that senescent decline is the combined effect of (1) uncompensated cellular attrition and (2) increasing histological entropy. Entropy increases due to a loss of the intra-tissue positional information that normally regulates cell fate and function. Informational loss is subject to positive feedback, producing the ever-accelerating pattern of senescence characteristic of iteroparous vertebrates. Though telomere erosion begins early in development, the onset of senescence should, on average, be deferred to the species-typical age of first reproduction, the balance point at which selection on this trade-off should allow exhaustion of replicative capacity to overtake some cell lines. We observe that captive-rodent breeding protocols, designed to increase reproductive output, simultaneously exert strong selection against reproductive senescence and virtually eliminate selection that would otherwise favor tumor suppression. This appears to have greatly elongated the telomeres of laboratory mice. With their telomeric failsafe effectively disabled, these animals are unreliable models of normal senescence and tumor formation. Safety tests employing these animals likely overestimate cancer risks and underestimate tissue damage and consequent accelerated senescence." @default.
• W2007509288 created "2016-06-24" @default.
• W2007509288 creator A5002260085 @default.
• W2007509288 creator A5027144959 @default.
• W2007509288 date "2002-05-01" @default.
• W2007509288 modified "2023-10-12" @default.
• W2007509288 title "The reserve-capacity hypothesis: evolutionary origins and modern implications of the trade-off between tumor-suppression and tissue-repair" @default.
• W2007509288 cites W111108193 @default.
• W2007509288 cites W1487697828 @default.
• W2007509288 cites W1493052311 @default.
• W2007509288 cites W1612842202 @default.
• W2007509288 cites W1666882487 @default.
• W2007509288 cites W1894632965 @default.
• W2007509288 cites W1966645907 @default.
• W2007509288 cites W1968222141 @default.
• W2007509288 cites W1968309671 @default.
• W2007509288 cites W1970894097 @default.
• W2007509288 cites W1976273464 @default.
• W2007509288 cites W1983650797 @default.
• W2007509288 cites W1983673827 @default.
• W2007509288 cites W1985112767 @default.
• W2007509288 cites W1986808310 @default.
• W2007509288 cites W1987603976 @default.
• W2007509288 cites W1998663807 @default.
• W2007509288 cites W2000971601 @default.
• W2007509288 cites W2004314923 @default.
• W2007509288 cites W2011482325 @default.
• W2007509288 cites W2035963497 @default.
• W2007509288 cites W2039819532 @default.
• W2007509288 cites W2043204829 @default.
• W2007509288 cites W2044444301 @default.
• W2007509288 cites W2050296416 @default.
• W2007509288 cites W2050473867 @default.
• W2007509288 cites W2062837346 @default.
• W2007509288 cites W2074433977 @default.
• W2007509288 cites W2075424154 @default.
• W2007509288 cites W2093588915 @default.
• W2007509288 cites W2139793739 @default.
• W2007509288 cites W2141926462 @default.
• W2007509288 cites W2144355145 @default.
• W2007509288 cites W2162303972 @default.
• W2007509288 cites W2171317581 @default.
• W2007509288 cites W2992097690 @default.
• W2007509288 cites W4237540956 @default.
• W2007509288 doi "https://doi.org/10.1016/s0531-5565(02)00012-8" @default.
• W2007509288 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11909679" @default.
• W2007509288 hasPublicationYear "2002" @default.
• W2007509288 type Work @default.
• W2007509288 sameAs 2007509288 @default.
• W2007509288 citedByCount "89" @default.
• W2007509288 countsByYear W20075092882012 @default.
• W2007509288 countsByYear W20075092882014 @default.
• W2007509288 countsByYear W20075092882015 @default.
• W2007509288 countsByYear W20075092882016 @default.
• W2007509288 countsByYear W20075092882017 @default.
• W2007509288 countsByYear W20075092882018 @default.
• W2007509288 countsByYear W20075092882020 @default.
• W2007509288 countsByYear W20075092882021 @default.
• W2007509288 countsByYear W20075092882022 @default.
• W2007509288 countsByYear W20075092882023 @default.
• W2007509288 crossrefType "journal-article" @default.
• W2007509288 hasAuthorship W2007509288A5002260085 @default.
• W2007509288 hasAuthorship W2007509288A5027144959 @default.
• W2007509288 hasConcept C104317684 @default.
• W2007509288 hasConcept C127716648 @default.
• W2007509288 hasConcept C141231307 @default.
• W2007509288 hasConcept C143425029 @default.
• W2007509288 hasConcept C177336024 @default.
• W2007509288 hasConcept C26207810 @default.
• W2007509288 hasConcept C2910240311 @default.
• W2007509288 hasConcept C522857546 @default.
• W2007509288 hasConcept C54355233 @default.
• W2007509288 hasConcept C552990157 @default.
• W2007509288 hasConcept C78458016 @default.
• W2007509288 hasConcept C86803240 @default.
• W2007509288 hasConceptScore W2007509288C104317684 @default.
• W2007509288 hasConceptScore W2007509288C127716648 @default.
• W2007509288 hasConceptScore W2007509288C141231307 @default.
• W2007509288 hasConceptScore W2007509288C143425029 @default.
• W2007509288 hasConceptScore W2007509288C177336024 @default.
• W2007509288 hasConceptScore W2007509288C26207810 @default.
• W2007509288 hasConceptScore W2007509288C2910240311 @default.
• W2007509288 hasConceptScore W2007509288C522857546 @default.
• W2007509288 hasConceptScore W2007509288C54355233 @default.
• W2007509288 hasConceptScore W2007509288C552990157 @default.
• W2007509288 hasConceptScore W2007509288C78458016 @default.
• W2007509288 hasConceptScore W2007509288C86803240 @default.
• W2007509288 hasIssue "5" @default.
• W2007509288 hasLocation W20075092881 @default.
• W2007509288 hasLocation W20075092882 @default.
• W2007509288 hasOpenAccess W2007509288 @default.
• W2007509288 hasPrimaryLocation W20075092881 @default.
• W2007509288 hasRelatedWork W1492321535 @default.
• W2007509288 hasRelatedWork W2084255033 @default.
• W2007509288 hasRelatedWork W2088926897 @default.
• W2007509288 hasRelatedWork W2109961065 @default.
• W2007509288 hasRelatedWork W2371502216 @default.
• W2007509288 hasRelatedWork W2461096401 @default.

• next