In which I get published

One great feature of the open access movement is that it’s democratized the act of reading a scholarly paper: you don’t need a subscription or an academic appointment, just access to a computer and a web browser.

But perhaps the OA folks have overly democratized the act of publishing a manuscript. Recent evidence suggests that they’ll let anyone do it.

Kidding aside: We’re pretty pleased about this paper, and we expect it to be the first of many from the Campisi lab on the general subject of secretion by senescent cells. Many of us are currently working on various aspects of the phenomenon, mostly on physiology and upstream regulation. Watch this space for further developments.

I can’t bring myself to blog seriously about papers I helped to write. If you’re interested, Abel Pharmboy has a detailed post over at Terra Sigillata; in it, he talks about the aging-cancer connection addressed within the paper. (Just to say it explicitly: I am not the first author of this study. Abel chose to interview me for the piece nbecause of our prior rapport and my involvement in science blogging).

Then again, it is an open-access paper, you can also check it out in primary form – perhaps, if you’re a nonspecialist, starting with the author summary.

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6 comments

  1. Congrats! It’s really amazing how much we’re learning about what’s going on in and around our cells as a result of research into cancer and aging (two sides of the same coin). It’s also cool that we are both interested in microenvironments – though of different types. 😛

  2. Congratulations,

    and just want to tell you I came across this paper prior to your post via another blog post and was impressed (and this was before I knew you are involved) – so the word is spreading quickly.

    brainhealthhacks.com

  3. Congrats,

    Interesting paper, I had never heard of SASP before. Upregulated secreation, heh? You state that the level of mRNAs encoding the SASP proteins increases – is it known whether this is solely the result of an upregulation in transcription and not an alteration in some other mRNA metabolic step such as a decrease in turnover? Also in order to acheive a higher level of secreation, are ER-proliferative programs activated? (This would obviously tie SASP back to your work on UPR.)

    And last question -is there a reason you used antibody arrays rather than SILAC mass spec?

  4. Thanks, Alex! And thanks also for the great questions. (For those of you who don’t know him, Alex is the author of The Daily Transcript; he also publishes in PLoS.)

    We coined the term SASP in the lab; there are a couple of papers from the Gil and Peeper labs published earlier in the year that also address cytokine secretion by senescent cells, so it’s been reported by others as well.

    We’re working on several questions related to mRNA metabolism right now, including turnover (doesn’t look like it) and differential translation (several lines of indirect evidence suggest this plays a role). First-line UPR experiments have come up empty, and we’ve never looked carefully at ER proliferation. A lot of these things are slated for the very near future. Actually, on the mRNA metabolism front, I have a couple of half-baked questions I plan to ask you at some point…

    Finally: Other than poverty, ignorance and the lack of a good core facility, there was no reason why we didn’t use mass spec. We’re about to move to the Buck Institute, where there is a quite nice mass spec facility, and I have a few ideas about how best to take advantage of it with regard to the SASP.

  5. Nice and complicated work, Chris et al!
    A discussion type question: Membrane ‘projections, tubes, protrusions’ (whatever they call and define it) are frequently associated with the senescent cellular phenotype, morphology in many cell types. Have you paid a little attention to the idea that those projections may have a role in the paracrine, near-field tumor-related mechanisms outside and complement to SASP? If yes, any experiments were figured out to measure their effects in intercellular communication?
    A practical question: What was the method to collect CM? How did you exclude all cellular contaminants from conditioned media? What about microvesicles under 100nm?
    Personal question: When are you moving to the Buck Institute?

  6. Thanks, Attila.

    The broad answer to your membrane-related questions is that we haven’t looked carefully at this issue.

    I’d be interested to hear thoughts about how to address the membrane protrusions. It seems like one would need a way to eliminate the protrusions while holding everything else constant — nothing obvious is coming to mind.

    The method for CM collection is fairly standard: pipet off the media, spin it at low speed to eliminate cell debris, and then filter at 0.2µ in order to eliminate cell fragments. Very small vesicles would still survive this harvesting method.

    Of course, anything inside these small vesicles would be undetectable to both the antibody arrays and the ELISAs we use to quantitate protein (since the proteins would be inside the membrane compartment) unless one imagines that the vesicles survive the harvesting technique only to burst when we quantitate proteins. We could certainly try exposing the samples to detergent and seeing whether this changed the amount of measured protein (though there would be challenges in terms of designing controls for such a method).

    So, to restate my first short answer: We haven’t done the right experiment to really answer the question. Vesicles would be easier to deal with than protrusions, as one could definitely ultracentrifuge, wash several times and then see what was left at the bottom of the tube (in terms of composition and/or biological activity).

    On that personal note: We’re going to move to the Buck sometime in mid-January. I just got my offer letter the other day, so it’s basically official.

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