Rapamycin for longevity: opinion article
https://doi.org/10.18632/aging.102355
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Abstract
From the dawn of civilization, humanity has dreamed of immortality. So why didn’t the discovery of the anti-aging properties of mTOR inhibitors change the world forever? I will discuss several reasons, including fear of the actual and fictional side effects of rapamycin, everolimus and other clinically-approved drugs, arguing that no real side effects preclude their use as anti-aging drugs today. Furthermore, the alternative to the reversible (and avoidable) side effects of rapamycin/everolimus are the irreversible (and inevitable) effects of aging: cancer, stroke, infarction, blindness and premature death. I will also discuss why it is more dangerous not to use anti-aging drugs than to use them and how rapamycin-based drug combinations have already been implemented for potential life extension in humans. If you read this article from the very beginning to its end, you may realize that the time is now.
“If you wait until you are ready, it is almost certainly too late.” Seth Godin
In one short-lived mutant strain of mice, the mTOR inhibitor rapamycin (known in the clinic as Sirolimus) extends maximum life span nearly three-fold [1]. Albeit less spectacularly, rapamycin also prolongs life in normal mice as well as in yeast, worms and flies, and it prevents age-related conditions in rodents, dogs, nonhuman primates and humans. Rapamycin and its analog, everolimus, are FDA approved for human use and have been used safely for decades. In 2006, it was suggested that rapamycin could be used immediately to slow down aging and all age-related diseases in humans [2], becoming an “anti-aging drug today” [3].
But rapamycin was unlucky
Rapamycin known in the clinic as Rapamune or Sirolimus, was unlucky from the start, however. Twenty years ago, it was labeled an immunosuppressant and used to treat renal transplant patients. If rapamycin had been labeled an immunomodulator and anti-inflammatory drug instead, it would sound much more appealing now. At anti-aging doses, rapamycin “eliminates hyperimmunity rather than suppresses immunity” or, more figuratively, it “rejuvenates immunity” [2]. This enables rapamycin and everolimus, a rapamycin analog, to act as immunostimulators [4–6], improving immunity in cancer patients [7] and the elderly [8,9]. For example, rapamycin reduces the risk of CMV infection in organ transplant patients [10–12], improves antipathogen and anticancer immunity in mice [13–15], prolongs lifespan in infection-prone mice [16] and protects aged mice against pneumonia [17]. Rapamycin also inhibits viral replication [18,19]. As a noteworthy example, rapamycin inhibits replication of the 1918 flu virus (the deadliest flu virus in history) by 100-fold [19], and also protects against lethal infection with influenza virus when administered during vaccination [13]. Still, as Dr. Allan Green advises, patients taking rapamycin should be carefully monitored for skin and subcutaneous bacterial infections, which should be treated with antibiotics https://rapamycintherapy.com.
Twenty years ago, it was thought that rapamycin might increase the risk of cancer (see a forthcoming review “Understanding the side effects of rapamycin”). Despite that concern, it was revealed that rapamycin actually prevents lymphoma and some types of cancer in transplant patients [20–27]. Currently, in fact, rapamycin analogs, everolimus and temsirolimus, are widely used in cancer therapy. Furthermore, rapamycin is the most effective known cancer-preventive agent in mice [25,28–32] extending the lifespan of cancer-prone mice [33–36]. It has even been suggested that rapamycin extends lifespan by preventing cancer [37].
Nevertheless, social media often warn that although rapamycin prevents cancer, its use to prevent cancer may come at the cost of getting cancer. This self-contradiction miscites a twenty-year-old warning by the FDA for all drugs marketed as immunosuppressants (including rapamycin and everolimus): “Increased susceptibility to infection and the possible development of malignancies such as lymphoma and skin cancer may result from immunosuppression.” This statement does not say that rapamycin or everolimus cause malignancies. (Just read it again). Although rapamycin and its analogs are now approved by the FDA for treatment of cancer and lymphomas, the rumors that these drugs may cause cancer persist. To my knowledge, no study has shown that mTOR inhibitors cause cancer.
At this point, most scientists agree that rapamycin is not counterindicated because of concerns about immunosuppressive effects. But a new objection against rapamycin has emerged, namely that rapamycin may cause diabetes. As discussed in detail [38], the new wave of “fear of rapamycin” is groundless. So, what are the metabolic effects of rapamycin?https://www.aging-us.com/article/102355/text
When people mention contemporary medicine, accuracy plays one of the most significant roles and people’s lives are literally dependent on it. Hereby, any researches pertaining to medicine are necessary to comply with the highest standards. The challenge nowadays is that any outcomes of researches can be published online and used as a reference without being adequately verified and validated. Mikhail (Misha) Blagosklonny of Oncotarget clearly understood this problem and decided to come up with an alternative solution. That’s how a weekly oncology-focused research journal named “Oncotarget” has been established back in 2010. The main principle of this journal is related to Altmetric scores that are used as a quality measure. That allows both readers and authors to validate publications with Altmetric Article Reports that generate “real-time feedback containing data summary related to a particular publication.” Oncotarget website has a full publications list with respective scores above 100 as well as reports mentioned previously. Mikhail (Misha) Blagosklonny glad to share his new approach and hopes it creates the necessary assistance to anybody, who has interest in oncology.
https://endnote.com/style_download/oncotarget/
“A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This paper was published back in 2018 by Oncotarget and written by different 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 mentions that “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 article has got an Altmetric score of 594. Mikhail (Misha) Blagosklonny realizes that most of readers are aiming 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.” Likewise, the article about melanoma, was used for citations in different news articles 69 times. Moreover, it was quoted 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 research 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 get useful scientific facts. Oncotarget is glad to have the chance to share with online customers this highly appreciated and high-quality information, that is trustworthy and reliable.
https://www.researchgate.net/profile/Mikhail_Blagosklonny
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