Hallmarks of Biological Failure/DanielPromislow

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Notes by user Daniel Promislow (Univ. Washington) 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

April 9, 2019

Charge for working groups

1. Come up with a list of major ideas/problems/concepts that you think we need to work on.
2. Think about what conceptual areas could be linked to better address the major questions discussed in #1.

Apr 8, 2019

A few thoughts about general questions for discussion:

1. What do we mean by "Biological Failure"? Aging? Senescence?
   1. Is there such a thing as a truly non-aging organism? An immortal organism?
2. Things that change with age...
   1. Why do so many things appear to increase exponentially, and in parallel on a log-linear scale, with age?
   2. Are there commonalities across other levels of organization with respect to how things change with age, and by 'things', this could be function, or selection, or failure.
3. What maintains variance among populations in aging. Even after controlling for G and E, we still see high levels of variance.
4. Issues of complexity/simplicity and networks were touched upon today, but we have not yet gone into detail, discussing this.

Bernie Crespi

Suggestions idea that complexity can be bad. We can think of organismal organization (and function and failure?) in a two-dimensional space of couple (loose<-->tight) and complexity (linear<-->high). Berni suggests (I think) that biological entities with high complexity (brains, immune system) are more prone to bring the entire system down with failure. Entities that are simple and loosely coupled are less likely to fail badly. Suggests a negative correlation between senescence and intelligence, though the GWAS data supporting this are problematic (like the recent study claiming to find genes for SES--https://www.biorxiv.org/content/10.1101/457515v1) are likely due to social stratification. Bernie's neologism of the day: badaptation.

Dario Valenzano

Comparative analysis of annual life history in killifish. Would benefit from Nathan Clark approach to look at rates of protein evolution in annual/perennial species: https://elifesciences.org/articles/25884. Expansion of mitochondrial genome is striking. I wonder if the finding of increase in genome size in the annual species is true of annual plant species (like corn and rice, which have very large genomes) relative to perennial plants.

James deGregori

Notion of adaptive oncogenesis, with stem cells well adapted to niche. As tissue ages, stem cells are no longer well adapted to the niche in which they find themselves. I wonder whether these models are also relevant to the selection process that happens *within* a tumor once cancer growth (and mutator phenotypes) is underway.

Roz Anderson

CR animals show a few major clusters of correlated -omic features, while AL animals show a very large number of small molecules. We should discuss just what these correlations mean, both statistically and biologically, and why these correlation structures (adjacency matrices) differ among the two groups so dramatically.

Tulja

Finishes talk with three general questions:

a. How strong is the trade-off between added longevity and lost fertility

b. Can we explain environmental plasticity?

c.  Does stochasticity matter? On any time scale?

For all three of these questions, I wonder if high-dimensional assays (metabolome, epigenome, etc) might have something to add to this discussion...

Sabrina Spencer

The technology that Sabrina is development could add tremendous power to the work now ongoing to track yeast cells as they age in real time. Also shows that quiescent cells are resistant to various stressors. Is that simply that they are metabolically quiescent and so not taking in these toxins?

Barb Natterson-Horowitz

Suggests that the disease-associated heart responses that we see could be maladaptive responses that evolved for adaptive reasons ('capture myopathy', 'alarm bradycardia'). Barb finds evidence for these phenomena in non-human species, but these could well be a large underestimate, simply because the vast majority of these events are never observed, and when observed, not reported.

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