On the web site of the aptly named pre-product biogerontology startup Legendary Pharmaceuticals, company founder John Furber has posted a compelling poster-sized flowchart of some key molecular events in aging.
By “some” I don’t mean that there are few (as should be clear from the complexity of the compressed version, below; click on it to see the full-size version); I simply mean that the list isn’t exhaustive, which isn’t a criticism — there’s plenty of information there to keep you busy. Besides, it’s sort of refreshing to see a discussion of cellular aging that altogether avoids mentioning sirtuins or insulin-like growth factor signaling.
The top tier focuses on molecular events (e.g., the accumulation of lipofuscins and the deposition of advanced glycation endproducts), in contrast to the activities of specific gene products (e.g., there is no “kinase A phosphorylates kinase B, which in turn phosphorylates kinase C”, though it is clear that author’s pet enzymes are getting special attention). I think this is a nice feature, since it allows the viewer to focus on the phenomenology of cellular aging rather than the details of specific protein action — in that sense, it would be an appropriate object on which to meditate if one were trying to brainstorm interesting subjects for future research.
The second and third tiers focus on cellular events and organ-tissue-level events, respectively, and likewise provide nutritious food for thought in the context of the applicability of molecular- and cell-level research to human disease and age-related health issues.
There are certainly criticisms to be leveled: Some of the arrows indicating causation are tenuously motivated by experimental observation. Conversely (as I sniped above), there are whole classes of environmental/behavioral influences, systems-level signals and critical lifespan-determining proteins that are ignored. Then again, the level of thoroughness achieved here is impressive, and I don’t think we can expect any one treatment to be truly comprehensive. Besides, as I said above, the focus on molecular events rather than protein action allows a more phenomenological focus, which can be valuable.
On another level: some of the proposed interventions (the green on the periphery) are a bit fanciful and somewhat reminiscent of the “aging is a solved problem, the details of which will be worked out by engineers” school of thought. On the other hand, someone has to dream the dreams, and many of the proposed interventions are quite reasonable, in theory if not immediately within the scope of current biological knowledge and existing biomedical technology (at least, not without a good deal more huffing and puffing from those sluggard pipet-jockeys down in the basic research division.)
Overall, though, I find the poster admirably ambitious, thought-provoking, and generally a Good Thing™. I’m going to print one out for our laboratory wall…just as soon as I can find a really large piece of paper.
(Hat tip to grailsearch.org, who posted on this yesterday.)
Printable wallchart of updated Aging Network Model
Submitted by John D. Furber (not verified) on Wed, 11/07/2007 – 09:02.
This Network Model Diagram has been updated. You may download a high-quality PDF file, formatted for printing on large-format paper, 36 x 48 inches (91 x 121 cm).
It is displayed on the page as a PNG file. To print a copy, scroll down to the link to the printable PDF.
Or, if you prefer to order a print, there are instructions for how to do that.
The web page also contains some explanatory material.
I welcome comments and feedback.
Cheers, - John D. Furber
Thanks for the excellent flowchart. It really encompasses various mechanisms that may be involved in aging.
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