To Fight COVID-19, Hasten Recovery, and Boost the Economy, AI Scientist Proposes Making Older People Younger

Coronavirus is the biggest public health and economic challenge of our time. The pandemic has been especially difficult for older people. People over 60 are at higher risk for infection, and once infected have substantially higher severity and lethality. When infected with COVID-19, people over 60 are more likely to have life-threatening diseases even if they are in good health. Although there are many treatments and vaccines currently in development to fight the virus, they are expected to be?less effective in older people.?This leaves 1 billion people over 60 in a vulnerable position especially if the virus returns.?Now is the time to develop innovative strategies for prevention and treatment of the virus in older people. At this critical point, we should actively use AI to address the major risks and challenges facing us.

In a paper published on March 31, 2020 in the journal, Aging,?Alex Zhavoronkov, PhD, chief scientist of the Biogerontology Research Foundation, proposes clinical trials for low-dose rapamycin individually and in combination with other geroprotectors to protect older people from COVID-19.?The paper is entitled?Geroprotective and senoremediative strategies to reduce the comorbidity, infection rates, severity, and lethality in gerophilic and gerolavic infections. In the paper,?Dr. Zhavoronkov proposes that since COVID‐19’s infection rates, severity, and lethality are substantially higher in the older population, innovative strategies for prevention and treatment should be used for this demographic. He proposes conducting clinical trials and meta-analysis of geroprotective and senoremediative strategies such as low-dose rapamycin once a week in combination with metformin and other low-cost accessible geroprotectors for prevention of SARS-CoV-2.

Dr. Zhavoronkov is chief scientist of the Biogerontology Research Foundation, the UK's leading non-profit focused on Longevity and ageing research. The Foundation has supported multiple initiatives relating to advancing Healthy Longevity. It provided financial and organizational support to Longevity International UK for the purpose of establishing the UK All-Party Parliamentary Group for Longevity, and to Ageing Research at King's for the purpose of establishing the Longevity AI Consortium at King's College London. The Foundation was also actively involved in the successful initiative to add a new extension code for "ageing-related diseases" accepted in 2018 by the World Health Organization during the last revisions of its International Classification of Diseases framework.

Dr. Zhavoronkov is CEO of Insilico Medicine a leader in next-generation AI for drug discovery, biomarker development, and aging research. Since 2015 he has invented critical technologies in the field of generative adversarial networks (GANs) and reinforcement learning (RL) for generation of the novel molecular structures with the desired properties and generation of synthetic biological and patient data. He also pioneered the applications of deep learning technologies for prediction of human biological age using multiple data types, transfer learning from aging into disease, target identification, and signaling pathway modeling.

Dr. Zhavoronkov suggests calling COVID-19 and other infections that are more harmful to the elderly?gerolavic infections. Gerolavic comes from the Greek words?geros?(old man) and?epilavís?(harmful). He proposes a strategy for repurposing known geroprotectors such as rapamycin, nicotinamide riboside, nicotinamide mononucleotide, metformin, and other drugs with a known safety profile for prevention of SARS-CoV-2 infection. He has analyzed the prior clinical studies of everolimus (RAD001) in healthy elderly people, and previous evidence showing paradoxical immunopotentiation effects of rapamycin and proposed additional clinical trials for these molecules in the healthy elderly population. Zhavoronkov also proposes the use of inexpensive and?minimally-invasive deep aging clocks?to track the efficacy of these preventative geroprotective interventions and to stratify the patients by predicted severity of COVID-19.?

While vaccination reduces infection rates, and therapeutic interventions reduce the severity and lethality of infections, these interventions have limitations in the elderly population. Previous studies showed that postulated geroprotectors, rapamycin and its close derivative rapalog everolimus decreased infection rates in a small sample of elderly patients. This article presents a review of the limited literature available on geroprotective and senoremediative interventions that may be investigated to decrease the disease burden of gerolavic infections.

Dr. Zhavoronkov is pursuing several strategies?for drug discovery?and repurposing using the latest advances in AI integrated into their battle-tested discovery platform. He hopes that this research will yield insights that will help with COVID-19 and also help prevent age-associated diseases. Furthermore, he believes that keeping older people healthy will re-ignite the economy and could potentially lead to unprecedented economic growth.

There is no clinical evidence yet showing age reversal or improved immune function in the elderly, but efforts are underway to identify new geroprotectors using AI and human data. There are?multiple databases of geroprotectors?and multiple strategies have been proposed to restore immune function in the elderly. To date the only known geroprotectors backed by promising clinical evidence of improved immune response to viral infection in the elderly are rapamycin and everolimus. Rapamycin is a well-known geroprotector, known to effectively slow aging in many species, including mice, and has been shown to delay age-related diseases in humans. However, no large clinical trials have been conducted yet.?

Dr.?Zhavoronkov’s paper presents a case for further research and clinical studies to validate markers of biological age in the context of viral infections. Ageing Research at King’s College London is partnering with?Biogerontology Research Foundation?and Insilico Medicine to identify mechanisms by which geroprotectors enhance resilience against infections and reduce the severity of symptoms. The proposed research will help physicians treat COVID-19, protect the elderly, and benefit long term global health and longevity.

Several companies are racing to create vaccines or drugs that target COVID-19 directly. These interventions will not offer complete protection, so adding geroprotectors may help improve the odds for the elderly. Interventions that enable immunocompromised elderly to mount an immune response to newly developed vaccines are necessary to help eradicate the disease and reduce the associated mortality. To avoid substantial loss of life among the elderly and vulnerable populations, governments and healthcare systems should investigate preventative and intervention strategies stemming from recent advances in aging research. Once the pandemic subsides, we will need to find ways to boost the economy. There are established models showing that the best way to grow the economy is by increasing healthy productive longevity.

Previously, Dr. Zhavoronkov proposed that increases in?productive longevity will substantially boost economic growth?in developed countries. Testing low-dose rapamycin individually or in combination with metformin, and NAD+ boosters such as nicotinamide riboside (NR), or nicotinamide mononucleotide (NMN) may help protect the elderly from gerolavic infection today and may also enhance economic recovery when the global pandemic is over.?Now is the time to develop?innovative strategies for prevention and treatment of COVID-19 in older people.?

This article was published in Forbes on March 31, 2020.

Interview with Dr. Zhavoronkov

This is interview with Dr. Alex Zhavoronkov in which he discusses the following:

1. Geroprotectors have the potential to prevent and treat COVID-19 in elderly patients, and we urgently need clinical trials to validate this.

2. Geroprotectors show promise in avoiding negative patient outcomes (lasting pathology and damage) in those who recover.

3. Longevity science can boost both the health of the elderly and the economic health of entire countries during the current COVID-19 crisis.

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Copyright ? 2020 Margaretta Colangelo. All Rights Reserved.

This article was written by?Margaretta Colangelo.?Margaretta is a leading AI analyst based in San Francisco. She serves on the advisory board of the AI Precision Health Institute at the University of Hawai?i?Cancer Center.?

Twitter?@realmargaretta