When a link doesn’t work, try googling a unique-looking prefix. In this case, ‘acel.12344’ looks like a unique ID. If I google “http://onlinelibrary.wiley.com/doi/10.1111/acel.12344/″, the first hit is http://onlinelibrary.wiley.com/doi/10.1111/acel.12344/abstract which is the paper “The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs”, Zhu & Tchkonia et al 2015 in Aging Cell; note that the journal sounds relevant, both Zhu and Tchkonia were mentioned by Darwin, the keyword ‘senolytic’ is present in the title, and the abstract reads:
The healthspan of mice is enhanced by killing senescent cells using a transgenic suicide gene. Achieving the same using small molecules would have a tremendous impact on quality of life and the burden of age-related chronic diseases. Here, we describe the rationale for identification and validation of a new class of drugs termed senolytics, which selectively kill senescent cells. By transcript analysis, we discovered increased expression of pro-survival networks in senescent cells, consistent with their established resistance to apoptosis. Using siRNA to silence expression of key nodes of this network, including ephrins (EFNB1 or 3), PI3Kδ, p21, BCL-xL, or plasminogen-activated inhibitor-2, killed senescent cells, but not proliferating or quiescent, differentiated cells. Drugs targeting these same factors selectively killed senescent cells. Dasatinib eliminated senescent human fat cell progenitors, while quercetin was more effective against senescent human endothelial cells and mouse BM-MSCs. The combination of dasatinib and quercetin was effective in eliminating senescent MEFs. In vivo, this combination reduced senescent cell burden in chronologically aged, radiation-exposed, and progeroid Ercc1−/Δ mice. In old mice, cardiac function and carotid vascular reactivity were improved 5 days after a single dose. Following irradiation of one limb in mice, a single dose led to improved exercise capacity for at least 7 months following drug treatment. Periodic drug administration extended healthspan in Ercc1−/∆ mice, delaying age-related symptoms and pathology, osteoporosis, and loss of intervertebral disk proteoglycans. These results demonstrate the feasibility of selectively ablating senescent cells and the efficacy of senolytics for alleviating symptoms of frailty and extending healthspan.
Hence you can be immediately confident that this must be the paper Darwin was linking. (Or if the link heuristic didn’t occur to you, you could have tried googling the buzzwords in Google Scholar; “senolytics senescent cells in vivo in rodents, and in human cell culture cells” would have turned up that paper as #5, and the preceding papers all look relevant too. And if that didn’t work, you could have searched “author:Tchkonia”, since it’s a highly unusual surname, and it would be #9 in Google Scholar.)
The paper can be downloaded from Wiley right now, but if it couldn’t, you could have still gotten a copy from Libgen.
I would be VERY interested in reading that http://onlinelibrary.wiley.com/doi/10.1111/acel.12344/pdf paper. Unfortunately the link does not work for me (page not found).
When a link doesn’t work, try googling a unique-looking prefix. In this case, ‘acel.12344’ looks like a unique ID. If I google “http://onlinelibrary.wiley.com/doi/10.1111/acel.12344/″, the first hit is http://onlinelibrary.wiley.com/doi/10.1111/acel.12344/abstract which is the paper “The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs”, Zhu & Tchkonia et al 2015 in Aging Cell; note that the journal sounds relevant, both Zhu and Tchkonia were mentioned by Darwin, the keyword ‘senolytic’ is present in the title, and the abstract reads:
Hence you can be immediately confident that this must be the paper Darwin was linking. (Or if the link heuristic didn’t occur to you, you could have tried googling the buzzwords in Google Scholar; “senolytics senescent cells in vivo in rodents, and in human cell culture cells” would have turned up that paper as #5, and the preceding papers all look relevant too. And if that didn’t work, you could have searched “author:Tchkonia”, since it’s a highly unusual surname, and it would be #9 in Google Scholar.)
The paper can be downloaded from Wiley right now, but if it couldn’t, you could have still gotten a copy from Libgen.
Thanks!
Huh after copying the link to my own post, it works! The link in the above post still does not. Weird!
It’s the period at the end of the link, which Darwin included to end the sentence and which you did not (because your sentence continued).