Rapamycin, proliferation and geroconversion to senescence

Rapamycin, proliferation and geroconversion to senescence

ABSTRACT

Rapamycin inhibits cell proliferation, yet preserves (re)-proliferative potential (RPP). RPP is a potential of quiescent cells that is lost in senescent cells. mTOR drives conversion from quiescence to senescence (geroconversion). By suppressing geroconversion, rapamycin preserves RPP. Geroconversion is characterized by proliferation-like levels of phospho-S6K/S6/4E-BP1 in nonproliferating cells arrested by p16 and/or p21. mTOR-driven geroconversion is associated with cellular hyperfunction, which in turn leads to organismal aging manifested by age-related diseases.

Introduction

In brief: proliferative potential is not actual proliferation

Rapamycin and other inhibitors of mTOR (mammalian Target of Rapamycin) maintain proliferative potential in non-proliferating cells [1,2]. This should not be misunderstood to mean stimulation of proliferation. In fact, rapamycin slows proliferation. The potential to proliferate is not actual proliferation; rather it is a hidden feature of quiescent cells that renders quiescence reversible. Rapamycin maintains the potential to proliferate in non-proliferating cells, enabling these cells can re-start proliferation when needed. We can use the term Re-Proliferative Potential (RPP) instead of proliferative potential to avoid confusion with actual proliferation -https://www.tandfonline.com/doi/full/10.1080/15384101.2018.1554781


When people refer to contemporary medicine, accuracy plays one of the most crucial roles and human lives are directly dependent on it. Hence, any researches pertaining to medicine are necessary to comply with the highest standards. The problem today is that any results of researches can be posted online and used as a reference without being adequately verified and approved. Mikhail (Misha) Blagosklonny of Oncotarget perfectly understood this issue and attempted to create an alternative solution. That’s how a weekly oncology-focused research journal named “Oncotarget” has been established back in 2010. The major principle of this journal is based on Altmetric scores that are used as a quality indicator. That allows both readers and authors to validate publications with Altmetric Article Reports that provide “real-time feedback containing data summary related to a particular publication.” Oncotarget website has a complete publications list with corresponding scores above 100 as well as reports discussed previously. Mikhail (Misha) Blagosklonny proud to share his new approach and hopes it creates the necessary help to anybody, who has interest in oncology.
https://www.crunchbase.com/person/mikhail-blagosklonny
“A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This study was published back in 2018 by Oncotarget and completed by various experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study discusses “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and shares an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
The publication has got an Altmetric score of 594. Mikhail (Misha) Blagosklonny realizes that most of readers are willing to understand the very meaning of it. Based on the Altmetric website, the score indicates “how many people have been exposed to and engaged with a scholarly output.” Hence, the paper about melanoma, was used for citations in different news articles 69 times. Besides that, it was mentioned in 2 online blogs, as well as 25 Tweets on Twitter and 1 Facebook post. FOX23 of Tulsa, Oklahoma has headlined their news on July 20, 2018 as “New blood test could detect skin cancer early”, using the main content of Australia study
Another Oncotarget’s study with a top score of 476, is “Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moon-shot,”. This study has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have seen a brief overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do receive helpful scientific facts. Oncotarget is proud to have the chance to share with online viewers this highly appreciated and high-quality information, that is trustworthy and reliable.
Misha Blagosklonny

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