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COMPLEX TIME: Adaptation, Aging, & Arrow of Time

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Difference between revisions of "Hallmarks of Biological Failure/MorganLevine"

From Complex Time
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{{Attendee note
|Post-meeting summary=I think one of the most interesting themes for me was the idea that aging may be less due to accumulation of damage, but rather, may reflect maladaptive responses to the aged-system or "aged environment". The idea that there may be multiple interacting complex systems that are designed (or evolved) to function in tandem (under certain innate environmental conditions set by neighboring/interacting systems). However with aging, the dysregulation that increases as a result of small perturbations in networks/systems (perceived as intrinsic environment changes) may acerbate aging in connect systems leading to an accelerated rate of failure sue to feedback. This also makes sense in terms of antagonistic pleiotropy--in a young system certain things are advantageous, yet as other systems fail, they may become maladaptive. This also is interesting in the context of heterochronic parabiosis in that exposure of an old animal to a young system or vice versa is advantageous/maladaptive.
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|Post-meeting summary=* Considerations of time-scales. Where/how is time encoded?
 
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* With time, new structures emerge, network connectivity changes
The other theme I found very interesting was the idea of modeling aging in the context of landscapes/wells that can be used to define the state of the organisms/system. Over time, the system will randomly sample other landscapes, yet have a propensity to move towards lower towards equilibrium. For the system, there may be a certain depth that corresponds to failure, which hypothetically could be reached via a multitude of paths. Finally, energy allocation or perturbation is needed to get over a hump, particularly to go back up to a higher level (further from equilibrium).
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* Can hyperactivity that optimizes growth and development contribute to aging (antagonistic pleiotropy)
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* Peto’s paradox—what things besides the number of cells, which should influence probably of neoplastic transformation, confer differences in species-level cancer risk?
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* Only the intercept, not the slope for the age-specific rates of lung cancer differ between smokers and never smokers.
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* May not be intrinsic damage accumulation and instead may be the difference of the “aged” vs. young environment which differentially selects for oncogenesis
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* Clonal hematopoiesis could be facilitated/accelerated by the old versus young environment?
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* How does this fit in to the findings from heterochronic parabiosis? Would changing the environment of the niche from old to you or vice versa alter 1) clonal hematopoiesis, or 2) probably of neoplastic transformation? What is the impact of HRAS in young versus old environment?
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* Aging may be both the small perturbations to the system and the reaction to perturbations in neighboring systems for which one depends on.  With a healthy neighbor idea, a small perturbation may not matter if the interacting system is functioning well, but ass the systems all go down hill together, there will be feedback that will cause an acceleration in the rate of multi-system declines. This may account for why things that change linearly with age, produce exponential morbidity/mortality cures at the level of the population.
 
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Revision as of 22:52, April 9, 2019

Notes by user Morgan Levine (Yale Univ.) for Hallmarks of Biological Failure

Post-meeting Reflection

1+ paragraphs on any combination of the following:

  • Presentation highlights
  • Open questions that came up
  • How your perspective changed
  • Impact on your own work
  • e.g. the discussion on [A] that we are having reminds me of [B] conference/[C] initiative/[D] funding call-for-proposal/[E] research group
  • Considerations of time-scales. Where/how is time encoded?
  • With time, new structures emerge, network connectivity changes
  • Can hyperactivity that optimizes growth and development contribute to aging (antagonistic pleiotropy)
  • Peto’s paradox—what things besides the number of cells, which should influence probably of neoplastic transformation, confer differences in species-level cancer risk?
  • Only the intercept, not the slope for the age-specific rates of lung cancer differ between smokers and never smokers.
  • May not be intrinsic damage accumulation and instead may be the difference of the “aged” vs. young environment which differentially selects for oncogenesis
  • Clonal hematopoiesis could be facilitated/accelerated by the old versus young environment?
  • How does this fit in to the findings from heterochronic parabiosis? Would changing the environment of the niche from old to you or vice versa alter 1) clonal hematopoiesis, or 2) probably of neoplastic transformation? What is the impact of HRAS in young versus old environment?
  • Aging may be both the small perturbations to the system and the reaction to perturbations in neighboring systems for which one depends on.  With a healthy neighbor idea, a small perturbation may not matter if the interacting system is functioning well, but ass the systems all go down hill together, there will be feedback that will cause an acceleration in the rate of multi-system declines. This may account for why things that change linearly with age, produce exponential morbidity/mortality cures at the level of the population.

Reference material notes

Some examples:

  • Here is [A] database on [B] that I pull data from to do [C] analysis that might be of interest to this group (insert link).
  • Here is a free tool for calculating [ABC] (insert link)
  • This painting/sculpture/forms of artwork is emblematic to our discussion on [X]!
  • Schwartz et al. 2017 offers a review on [ABC] migration as relate to climatic factors (add the reference as well).

Reference Materials