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Progeria, rapamycin and normal aging: recent breakthrough

Progeria, rapamycin and normal aging: recent breakthrough



Abstract

A recent discovery that rapamycin suppresses a pro-senescent phenotype in progeric cells not only suggests a non-toxic therapy for progeria but also implies its similarity with normal aging. For one, rapamycin is also known to suppress aging of regular human cells. Here I discuss four potential scenarios, comparing progeria with both normal and accelerated aging. This reveals further indications of rapamycin both for accelerated aging in obese and for progeria.

In the last week paper in Science Transl Med, Francis Collins, Dimitri Krainc, Kan Cao and co-workers described that rapamycin reverses cellular phenotypes in Hutchinson-Gilford progeria syndrome (HGPS) cells [1]. Is it a co-incidence that rapamycin also suppresses senescence in regular (non-HGPS) mammalian cells [2]?

Clearance of progerin by rapamycin

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by some features reminiscent of aging, including atherosclerosis and alopecia [3-6]. The median life span is 13 years, and the main cause of death is myocardial infarction and stroke. Progeria is mainly caused by the abnormal accumulation of progerin, a mutant form of the nuclear envelope component lamin A [7, 8]. In cell culture, HGPS cells are prone to replicative senescence (Figure 1) [9-12]. Accumulation of progerin causes nuclear abnormalities, mitotic abnormalities and accelerate telomere shortening. This causes DNA damage response, p53 induction and cell cycle arrest [11, 13-16]. After a number of cell divisions in culture, cells stop proliferating (replicative senescence).

Very recently Cao et al described that rapamycin stimulates clearance of progerin and therefore prevents nuclear abnormalities and delays replicative senescence [1]. Rapamycin eliminates the cause of the abnormalities and therefore is expected to be an effective treatment in progeria [1]. In addition to this strong rationale [1], there is one additional indication for rapamycin, regardless of progerin clearance, namely suppression of geroconversion (conversion from quiescence to senescence) by rapamycin [2, 17-19].  https://www.aging-us.com/article/100352/text

oncoscience impact factor Zoya Demidenko Dr. Zoya N. Demidenko Zoya N. Demidenko , Ph.D. is Executive Manager of the Oncotarget journal . Oncotarget publishes high-impact research papers of general interest and outstanding significance and novelty in all areas of biology and medicine: in translational, basic and clinical research including but not limited to cancer research, oncogenes, oncoproteins and tumor suppressors, signaling pathways as potential targets for therapeutic intervention, shared targets in different diseases (cancer, benign tumors, atherosclerosis, eukaryotic infections, metabolic syndrome and other age-related diseases), chemotherapy, and new therapeutic strategies. After earning her Ph.D. in molecular biology, Zoya was awarded a Fogarty post-doctoral Fellowship from the National Institutes of Health in Bethesda, MD. After successful completion of post-doctoral training, she continued her professional career at George Washington University and Albert Einstein School of Medicine . In 2005 she cofounded the startup company Oncotarget Inc. which is focused on the development of anti-aging and anti-cancer drugs. Her research interests include signal transduction, cell cycle and cellular senescence, and their pharmacological targeting. In 2009 she cofounded the publishing house Impact Journals which specializes in publishing scientific journals. In 2011 she was selected to be a Member of the National Association of Professional Women .


When general population speak of contemporary medicine, accuracy plays one of the most significant roles and people’s lives are literally dependent on it. Hence, any researches related to medicine are required to meet the top standards. The challenge nowadays is that any recommendations of researches can be shared online and used as a reference without being precisely checked and validated. Mikhail (Misha) Blagosklonny of Oncotarget clearly understood this problem and tried to come up with an alternative solution. That’s how a weekly oncology-focused research journal called “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 quality-check publications with Altmetric Article Reports that provide “real-time feedback containing data summary related to a particular publication.” Oncotarget website provides a complete publications list with respective scores higher than 100 as well as reports discussed above. Mikhail (Misha) Blagosklonny glad to share his new approach and hopes it creates the required help to anybody, who has interest in oncology.
“A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This paper was released back in 2018 by Oncotarget and completed by several 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 provides 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 majority of readers are willing to comprehend 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 article about melanoma, was utilized for citations in different news articles 69 times. In addition, it was referred to 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 publication has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have seen a concise overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do get helpful scientific facts. Oncotarget is happy to have the chance to share with online readers this highly appreciated and high-quality information, that is trustworthy and reliable.

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