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1+ paragraphs on any combination of the following:
(1) General problem/question
DNA/RNA/proteins - cells - cell-to-cell interactions - tissues - organs - organ systems - whole organism - groups of related organisms as in colony - community including non-relatives
how/why does senescence occur at these different levels, in the contexts of antagonistic pleiotropy and mutation accumulation? does balance of early benefits vs later costs vary across these levels and systems?
does the complexity/stability/entropy of the system matter? how?
why does senescence accelerate exponentially in humans - synergisms between failure types/levels? why up so fast around age 60-65 in particular (later for women)-becoming less useful as a helper/contributor/transfer-er then, and are being 'replaced' these roles by next generation?
(2) Caloric restriction - reduces deleterious aging effects on health but does not lengthen lifespan if started after adulthood - why not? increases investment in maintenance, reduces growth and reproduction, based on energy, thus mitochondria
all cells use energy - does energy restriction impact some cells/systems more (eg brain if not fully protected); or are all systems just ramped down - how does this impact on disease risks, exactly - do diseases require more energy? or are fewer mistakes/mutations made?
(3) Single cell talk p21. Is this work key to cancer biology in that tumor suppressor functions being lost leads to all cells just keeping reproducing? can one show that senescent cells are less likely to transform, using this system?
(4) Idea that senescence is an emergent property (of defense against worse failures) appears quite important to me
(5) Comparing biological failure between organisms and higher 'levels' (societies, civilizations, ecosystems, etc): how might societies/civilizations age in same way lower-level systems do? maintain current system even when its benefits decline, due to environmental or other change? external causes of increased weakness of units at different levels? Fit with Jared Diamond's ideas about Collapse of civilizations? (what were those need to check).
Parallel causes, biology and higher levels - complexity and coupling of components? Too much investment in defense? (Russia 1991)
DAY 2 questions
how do CR genes relate to antagonistic pleiotropy?
what are roles of germline mutation in relation to somatic mutations in senescence?
intelligence/brain size related to aging/senescence both within and between species (and related to CpG calendar/clock methylation) - why? do immune systems have 'intelligence'? (measure of their efficiency of functioning in some manner).
why length of post-reproduction life vary (esp females) - fewer stresses when young? more resilient senescence system? other? related to intelligence (more than pre-menopause lifespan)?
age around 60 represent tipping point into accelration of aging effects/disease risks? synergistic failure across systems?
adaptive landscape model - flatten with age as selection weakens, lower adaptive peaks? mutation moves you downhill easier?
prioritization of organ systems with age - how vary - costs of degradation is each system? brain, immune at top.coindcides with ability to trade off across systems, higher->less prioritization
aging and loss of information in networks, higher entropy, protein folding, feedbacks in networks, how measure these changes, chaperones, perturb system like insulin challenge test in pregnancy
DAY 3 thoughts, questions
How well does theory interface with data in study of aging?
Agendas of proximate-mechanisms, biomarker geroscience researchers how much integrate evolutionary or other theory insights, how useful will they be for advancing theory?
Crispr on CR genes then analyze behavior of cells/tissues across age
CR genes for maintenance (rheostat) how much trade off with growth and reproduction genes, strong theory predictions here
[aside: do empiricists who focus on specific function tend to not think about tradeoffs (in evolutionary contexts) because they involve competing/beneficial but incompatible functions?]
DIfferent organ systems ought to senesce at different rates