Dynamic Multi-System Resilience in Human Aging/Welcome & introduction around the Room

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November 12, 2018
9:30 am - 9:45 am

Presenter

Marcel G.M. Olde Rikkert (Radboud Univ.), Tim Buchman (Emory Univ./SFI)

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Post-meeting Reflection

Marcel G.M. Olde Rikkert (Radboud Univ.) Link to the source page

I was amazed by the alternative vision of Dervis Can Vural about damage accumulation and aging in random network perspective. Among others it again helped me realize that downstream targeted therapies in chronic age related diseases (which mostly are directed by mechanisms of aging) probably are not to be of great help. The connections of nodes higher upstream, still being damaged or producing damage will still end up in causing the disease related decline.

The presentation of Peter Hofmman showed an elegant 'simple model' of stochastic damage accumulation and repair. It opened the perspective of ramdoness in resilience mechanisms, when the redundancy of reserve function has depleted. The three trajectories of damage and death occurence are very interesting, and I look very much forward to the statistical analyses of these data, after repeated runs of these models.

The talk of Alfons Hoekstra, showed that the multiscale modeling is fit for supporting resilience research and so is fit for being part of the workshop (though he humbly stated that multiscale modeling might not be mature enough for this challenge). The examples Alfons showed in the time -space scaling diagrammes and the connecting interactions do inspire to connect and likewise model subsystems depending on one another and creating a meaningful representation of challenges for aging persons.

Ravi Varadhan and Chhandi Dutta gave an excellent overview of the research grants given in the field by the NIA, and the models already published, respectively. These are excellent sources of comparison for further work.

Second day, we had a very inspiring lecture of Ingrid vd Leemput. The theoretical and empirical reasoning and analyses of ecosystems can be of great help in studying resilience systems in aging man.

Heather Whitson followed up with a nice clinical example. But not only the patient but also the family and physicians make up a complex adaptive system. She also paved the way to stress tests of different kinds, which was completed later on nicely by Warren Ladiges on animal models. This connection added new insights and clearly showed that beside computational models, the animal models are very valuable.

Last but not least Porter Swetsell gave eye openers on population resilience based on his scholarly and personal experiences with pueblo population resilience over time. These all got intertwined in the group discussion, which also opened up new opportunities for collaboration.

The meeting so far showed emergence of many new options, and warrants, inspires aand invites for further interaction and collaboration.

Tim Buchman (Emory Univ./SFI) Link to the source page

An excellent first day. We heard theory-based perspectives and came directly upon the challenges of human subjects research. The theory based perspectives from Dervis Vural, Peter Hoffmann, and Alfons Hoekstra illustrated the (relative) simplicity of models that effectively abstract and recapitulate several well-recognized characteristics of human aging and frailty. Yet human-derived data are messy, do not lend themselves easily to hypothesis testing because they are so often observational and incomplete, and are confounded by the outbred nature of humans, their varying allostatic loads, and the variety of acute-on-chronic illnesses that bring them to research studies and/or clinical care.

The most interesting part of the second day, perhaps, was the presentation on resiliency among the indigenous peoples of NM. It became quite clear that the ability to (re)generate networks and interactions was foundational to regenerating the population. A reasonable inference , and mirroring Dervis Vural's presentation on Day 1, is that the capacity to reconstruct networks is foundational to resilience. It is unclear whether it is the ability to reconstruct some evolutionarily specified or developmental network is required, or rather a more general capacity. But "fixing a failed node" is unlikely to work unless that failed node is the foundational "network spawner".

The need for a marker that reliably informs clinicians that the capacity to recover from perturbation is now (and forever) exhausted is apparent. The problem around end of life is acknowledging that it is indeed end-of-life, that the physiological derangement exceeds reparative capacity, with or without the stabilization that clinicians can provide. As technical medicine gets better at dealing with minutiae, such markers of inevitable collapse become even more important. As a reminder, 27% of the US Medicare budget is routinely spent in the last year of life, with a substantial uptick in the last month as part of the "rescue phantasy" to use Freud's term. "slowing" and delayed correction of spontaneous or engineered perurbations is a start, but seems by itself insufficient as a basis for clinical decision making.

Reference Material

Title	Author name	Source name	Year	Citation count From Scopus. Refreshed every 5 days.	Page views	Related file
To adapt or not to adapt: consequences of declining adaptive homeostasis and proteases with age				0	4

Title	Author name	Source name	Year	Citation count From Scopus. Refreshed every 5 days.	Page views	Related file
The community of the self	Timothy G. Buchman	Nature	2002	157	14
The community of the self2	Timothy G. Buchman	Nature	2002	157	14
The community of the self3	Timothy G. Buchman	Nature	2002	157	8
Uncoupling of Biological Oscillators				0	2
Community of the Self				0	0