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COMPLEX TIME: Adaptation, Aging, & Arrow of Time

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Aging in Single-celled Organisms: from Bacteria to the Whole Tree of Life/SabrinaSpencer

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Notes by user Sabrina Spencer (CU Boulder) for Aging in Single-celled Organisms: from Bacteria to the Whole Tree of Life

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

What is holding back the field of aging? First is a definition of aging, which we have generally agreed represents deterioration of function. Second then, is how to measure deterioration of function. We lack good markers for most relevant items at the single-cell level: 1. Cumulative DNA damage, 2. Telomere length, 3. Oxygen consumption rate, 4. Presence of original or newly replicated DNA strand. 5. epigenetic clock measured by DNA methylation.

Of course, there are single-cell DNA damage markers, but as far as I know, they only mark current existing mismatches, damaged bases, single-strand or double-strand breaks etc, but not cumulative damage. The need for a cumulative/historical marker speaks to the idea Sri proposed that aging requires a cellular memory - something needs to be accumulated as cells age, otherwise cells would not know or have an age. While a snapshot of telomere length does contain a historical record, telomere length and oxygen consumption rate are easily measured on a population level, but not in single cells. The single-cell aspect is important because while telomere length decreases with increasing passage number, Martin Picard showed that telomere length does not correlate with when a population hits its Hayflick limit. This may well be because what cells care about is the shortest telomere in a cell, not the population telomere length. Tracking the immortal strand is technically difficult. For the epigenetic clock measured by DNA methylation, the conceptual link with deterioration of function is unclear.

Then there's the ability to return to homeostasis as a general definition of aging, but how to measure that is unclear.

The one thing that can currently be measured in single cells both in a snapshot and over time is protein aggregation. Lin Chao measures this with IBPA-GFP. Maybe measuring protein aggregates is our best bet since that is measurable and since it has been shown to cause dysfunction, particularly in neurons.

Meeting statements:

  1. Aging is the cost organisms pay to have offspring that are free of damage.
  2. Aging is a spandrel
  3. Aging is a consequence of the chemical reactions, energy flux, 2nd law, etc. needed for life.
  4. Asymmetry is inevitable.
  5. The parent cell will be defined here as the cell that accepts the majority of the damage.
  6. Which damaged components matter the most is unclear (e.g. old pole protein, mitochondria, immortal strand)
  7. Therefore, there will be no universal marker for aging (more granular: damage)  and what we need instead is various functional definitions that are context dependent (when can we project this onto fitness of vice versa)?
  8. The major issue is that we don’t have the right data or know what to measure? ie We don’t know the currency of aging.

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).

Baker DJ, Childs BG, Durik M, Wijers ME, Sieben CJ, Zhong J, Saltness RA, Jeganathan KB, Verzosa GC, Pezeshki A, Khazaie K, Miller JD, van Deursen JM. Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature. 2016 Feb 11; 530 (7589):184-9 Epub 2016 Feb 03

Reference Materials