Hallmarks of Biological Failure/MorganLevine

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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

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.

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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