February 11, 2021. Conference and workshops. Clarifying whether and to what degree the current anti-aging approaches work in mice or people.

On the occasion of the next online conference to be held on Thursday, February 11, 2021, from 17:00 to 22:00 PM CET (8.00 AM to 1 PM PDT, 11.00 AM to 4 PM EDT),

we will invite renowned scientists to give an overview of effective anti-aging studies performed on mice or rats as well as the most recent tests performed on humans.

You can register here

The complete conference recording

Thursday, 11 February

17:00 – 17:15  Introduction Didier Coeurnelle, Ilia Stambler, Sven Bulterijs

1. Test on mice/ rats: good practices

17:15 – 17:30  Conboy Mike “Resetting Aged Blood to Restore Youth”

17:30 – 17:45 Vera Gorbunova  “ Promoting longevity by improving genome stability “

17:45 – 18:00  Rodolfo Goya  “ Aging and epigenetic rejuvenation”

18:00 – 18:15   Josh Mitteldorf  “interactions among interventions, and why we can’t just test them separately”.

18:15 – 18:25  Pause

2. Test on human: good practices

18:25 – 18:40   Nir Barzilai “TAME (Targeting Aging with Metformin)”

18:40 – 18:55  Harold Katcher “Breakthrough in age reversal with young blood plasma”

18:55 – 19:10  Greg Fahy “Reversal of epigenetic aging and immunosenescence trends in humans” Aging Cell

19:10 – 19:25 Hanadie Yousef (Juvena Therapeutics)  “Harnessing the regenerative secretome of human embryonic stem cells to rejuvenate aged tissues”

19:25 – 19:40  Liz Parrish “Gene therapy to reduce the effects of aging”

19:40 – 19:55 Justin Rebo (BioAge)

19:55 – 20:00 Martin Lipovšek “Slovenian Levine clock project”

20:00 – 20:10 Edouard Debonneuil “Of mice and men: from the Major Mouse Testing Program to the Major Human Testing Program”

20:10 – 20:20 Pause

3. From rats to humans and the other way around? Legal, scientific, technical, and political aspects. concerning Clinical tests

20:20 – 20:35 Mimicking experimentation on rats and humans thanks to A.I.?  Alexander Zhavoronkov, and /or Polina Mamoshina

20:35 – 20:50 . How to  accelerate. Political and legal aspects Didier Coeurnelle

20:50 – 21:05. Have the anti-aging interventions worked? Some lessons from the history of anti-aging experiments on animals and humans. Ilia Stambler

21:05 – 21:15 Pause

4. Discussion about the 3 themes in 3 groups. Goal: one page of thoughts and proposals for each group

21:15 – 22:00 Divided in 3 zoom spaces

Rats Chair Irina Conboy and Marion
Human tests Chair Aubrey de Grey
Political aspects Alexander and Didier

5. Conclusion and goodbye

The next day, Friday, February 12 (8 – 9.30 PM CET)
Finalization of the 3 texts of thoughts and proposals (discussion on line)

This temporary program is subject to change

The novel coronavirus disease 2019 (COVID-19) has grown to become a global public health emergency. Currently, no specific drugs or vaccines are available to cure the patients with COVID-19 infection. Hence, there is a large unmet need for a safe and effective treatment for COVID-19 infected patients, especially the severe cases. There are emerging several promising directions for therapy development.

Thus, good initial results were shown by the use of stem cells, in particular the intravenous transplantation of mesenchymal stem cells (MSCs) into severe COVID-19 patients [1]. The main cause of life-threatening conditions, disability and death in COVID-19 patients may derive from an excessive inflammatory response to the virus, leading to the major complications of cytokine storm in the lung, disrupting the balance of cytokines, followed by edema, dysfunction of the air exchange, acute respiratory distress syndrome (ARDS), acute cardiac injury and secondary infections, which may lead to death.  Treatments, like MSCs could inhibit the over-activation of the immune system and promote endogenous repair by improving the microenvironment, thus they could represent a safe and effective treatment for patients with COVID-19 pneumonia, especially for the patients in critically severe conditions.

Yet, there may be additional or complementary methods to potentially fight excessive inflammation and the resulting cardio-respiratory problems, such as ARDS.

One of the potential therapeutic approaches is Hyperbaric Oxygenation Therapy (HBOT). HBOT or high pressure oxygen delivery has been gaining an increasing recognition as a versatile therapeutic approach, including diverse severe and critical conditions [2].

The HBOT general protective effect on the organism may be due to its improving energy metabolism. In many ICU cases, with a multiple range of severe indications, HBO treatment improved the survival and prevented multiple-organ failure, including preventing damage of the lungs. HBOT demonstrated protective, even life-saving effects against the most severe cardio-respiratory complications, including Acute Respiratory Distress Syndrome (ARDS), leading to a normalization of the gas exchange in the lungs and pumping function of the heart, thus preventing lethality in the patients [2].

The cardio-respiratory complications are the main cause of suffering and death also in severe COVID-19 patients. Hence the application of HBOT may be suggested as an investigational treatment for these patients.

In COVID-19, the life-threatening complications are mostly due to an excessive inflammatory response. The HBTO mechanism of action may become beneficial for such patients, since HBOT has been commonly reported to produce anti-inflammatory effects, which have been implicated as one of its major therapeutic mechanisms, for both age-related chronic and acute conditions. The protective physiological function of HBOT may further involve improvement of myocardial contraction, endogenous production of lung surfactants and corticosteroids, and anti-microbial effects.

In certain acute cases, regular ventilation may be insufficient to supply enough oxygen for the vital function of severely ill patients. The inclusion of high pressure oxygen delivery by HBOT may facilitate a more rapid recovery of vital functions and save the patients. So far hyperbaric oxygenation remains one of the most effective clinical means of oxygen delivery to deep vital tissues, hence promising for the treatment of severe consequences of the cardio-respiratory impairment generally, and in severe or critical COVID-19 patients in particular.

To the best of our knowledge, an application of HBOT against COVID-19 has not yet been practically attempted. We suggest investigating this possibility, utilizing the best existing HBOT expertise, to maximize potential benefits while preventing adverse side effects.

It must be noted that the question about the efficacy of using HBOT against acute severe impairments of vital thoracic organs (such as ARDS and others) is still debated [2]. Apparently, a necessary condition to achieve effective therapy should be proper HBO dosing, which necessitates acquiring data on dose effects in each pathological state, with close multi-parametric real-time monitoring, while maintaining strict safety conditions, to minimize infection and prevent over-stimulation and oxygen toxicity. Therapeutic regimens need to be adjusted to age-specific responses in the elderly and multi-morbid patients as compared to the younger patients, whose therapeutic regimens and benefits may be different. Further regimen distinctions should be made for HBOT under acute conditions (emergency HBOT) vs. chronic conditions (maintenance HBOT) vs. preclinical conditions (preventive HBOT). The regimens, dosages, toxicities and risk factors under the different conditions will require investigation during the trial application.

Yet, we believe, that following the differential proof of concept investigation, hyperbaric oxygen therapy may become a life-saving resuscitation measure for COVID-19 patients, who have urgent oxygen requirements and high inflammatory response.

Gennady Rogatsky, MD, PhD. Faculty of Life Sciences. Bar Ilan University, Israel (emeritus).

Ilia Stambler, PhD. Shmuel Harofe Geriatric Medical Center, Israel

Selected sources 

[1] Zikuan Leng, Rongjia Zhu, Wei Hou, Yingmei Feng, Yanlei Yang, Qin Han, et al. (2020). Transplantation of ACE2- mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia. Aging and Disease, 11(2):216-228 http://www.aginganddisease.org/article/0000/2152-5250/ad-0-0-216.shtml

[2] Gennady G. Rogatsky and Ilia Stambler (2017). Hyperbaric oxygenation for resuscitation and therapy of elderly patients with cerebral and cardio-respiratory dysfunction. Frontiers in Bioscience, 9:230-243. https://www.bioscience.org/2017/v9s/af/484/fulltext.htm

Downlad the open letter as PDF

Hyperbaric Oxygen Therapy against COVID-19

See also

Rogatsky and Stambler – HBOT in Elderly – Frontiers in Bioscience 9, 230-243, 2017

In Russian

HBOT – Russian – 2017

Update 16 October 2020

The (initial encouraging) results of using Hyperbaric Oxygen Therapy against COVID-19 have been published. The HBO treatments were done in Moscow N.V. Sklifosovsky Research Institute for Emergency Medicine. The article entitled “The Safety of Hyperbaric Oxygen Therapy in the Treatment of Covid-19” was published in the Russian Sklifosovsky Journal of Emergency Medical Care (the article is in Russian, with an abstract in English).

https://cyberleninka.ru/article/n/bezopasnost-primeneniya-giperbaricheskoy-oksigenatsii-pri-lechenii-covid-19

According to the abstract: “We examined 32 patients with the diagnosis “Coronavirus infection caused by the virus SARS-CoV-2” (10 — moderately severe patients (CT 1–2), 22 — patients in serious condition (CT 3–4), who received course of hyperbaric oxygenation (HBO). … the patients showed an increase in blood oxygen saturation in patients in both surveyed groups, as well as positive dynamics in the form of a decrease in shortness of breath, an improvement in general well-being.”

According to the article “No patients in both groups under HBO treatment required transfer to artificial ventilation.”

https://www.rbc.ru/society/05/06/2020/5ed9d9519a7947f8f0c45ff4

https://www.youtube.com/watch?v=e0H6zPzfXNs&t=2112s

Update 11 August 2022. Another work by the same institute

HYPERBARIC OXYGENATION IN THE COMPLEX FOR LONG-COVID-INFECTION REHABILITATION MEASURES – THERAPIA 5 2022 RUSSIAN

And an Israeli work (July 2022)

https://www.gov.il/en/departments/news/tau-researchers-develop-treatment-for-long-term-covid-19-symptoms-20-jul-2022

https://www.nature.com/articles/s41598-022-15565-0

By Ilia Stambler, PhD

The novel coronavirus disease 2019 (COVID-19) has grown to become a global public health emergency. Currently, no specific drugs or vaccines are available to cure the patients with COVID-19 infection. Hence, there is a large unmet need for a safe and effective treatment for COVID-19 infected patients, especially the severe cases.  A new study offers a promising pathway for developing such a treatment.

The new approach involves intravenous transplantation of mesenchymal stem cells (MSCs) into the patients. It was successfully tested in 7 COVID-19 patients, in Beijing YouAn Hospital, Capital Medical University, China. The results are published in the scientific journal Aging and Disease, entitled “Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia”.

https://doi.org/10.14336/AD.2020.0228

The study was conducted by a team led by Dr. Robert Chunhua Zhao, with Shanghai University and Chinese Academy of Medical Sciences & Peking Union Medical College, China.

Moreover the study was reviewed by a scientific committee of the International Society on Aging and Disease (ISOAD) and the recently established UNESCO-affiliated committee on Anti-Aging and Disease Prevention http://www.aginganddisease.org/EN/10.14336/AD.2019.1230

Based on the 14 days observation, MSCs could cure or significantly improve the functional outcomes of all the seven tested patients without observed adverse effects, contrary to 3 controls. The pulmonary function and symptoms of these seven patients were significantly improved after MSC transplantation. Among them, one severe and two common patients recovered and were discharged in 10 days after the treatment. The improvement was particularly dramatic for an elderly (65 y.o.) male patient in severe critical condition. All of his primary and secondary outcomes improved: the inflammation status, the oxygen saturation, and the functional biochemical indicators returned to normal reference values in 2~4 days after the treatment.

The presented evidence suggests that the therapeutic effects are based on the immunomodulatory capacity of mesenchymal stem cells (restoring the balance of the immune system). The coronavirus infection can stimulate a terrible cytokine storm in the lung, disrupting the balance of cytokines (signaling molecules of the immune system) such as IL-2, IL-6, IL-7, GSCF, IP10, MCP1, MIP1A and TNFα cytokines, followed by the edema, dysfunction of the air exchange, acute respiratory distress syndrome, acute cardiac injury and the secondary infection, which may lead to death.  The bone-marrow derived MSCs could inhibit the over-activation of the immune system and promote endogenous repair by improving the microenvironment, thus they could represent a safe and effective treatment for patients with COVID-19 pneumonia, especially for the patients in critically severe conditions. A larger validation study is required and is already underway, yet the initial results are encouraging.

Notably, the coronavirus-infected pneumonia is more likely to affect older individuals, especially older males, with comorbidities, resulting in their severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In other words, aging appears to be the main risk factor for bad outcomes. However, the cure essentially depends on the patient’s own immune system. When the overactivated immune system kills the virus, it produces a large number of inflammatory factors, leading to the severe cytokine storms. This suggests that the main reason for the organs damage may be the virus-induced cytokine storm. Older subjects may be much easier to be affected due to immunosenescence. The study showed remarkable recovery of the elderly patients thanks to restoring their immune function.

Thus, the study may have a broader significance, even beyond the treatment of the severe coronavirus disease. This study exemplifies that the general therapeutic improvement of the immune system in the elderly can improve outcome and survival, which may have more general relevance for other aging-related communicable diseases. Thus, this study may inspire and pave the way for further promising directions to investigate the connection between aging and disease, and to treat both communicable and non-communicable aging-related diseases.

The Romanian journalist Laura Ștefănuț spoke with Dr. Ilia Stambler about the broader implications of this research. Ilia Stambler is a co-author in this study who was involved in the study review, interpretation and discussion. He serves as the Outreach Coordinator of the International Society on Aging and Disease (ISOAD) and Director of Research and Development at Shmuel Harofe Geriatric Medical Center in Israel.

Q: How does it feel to be part of the team which discovered a groundbreaking treatment for what is currently considered one of the biggest global challenges?

A: I feel very honored to be included in this extended international team. I hope this team continues its work that will also involve additional collaborations.

Q: As a researcher, what did you find most interesting about this novel coronavirus? What seems most threatening about this new virus?

A: The spreading ability of this virus is relatively high and it has the capacity to affect the entire global population. This is what makes this virus a particularly strong concern for global public health. The social effects of this epidemic are also of great importance. In a sense, this virus is testing the strength of our public health systems. Will the immunity of our public healthcare be strong enough to contain it? I hope it is.

Q: Did the discovery of this groundbreaking new therapeutic approach make you more optimistic (when it comes to containing and limiting the damage of Covid-19)? In which sense (where was your optimism before the discovery)?

A: I was optimistic before, as I believe that, same as for many infectious diseases in the past, also for this disease, effective therapeutic and preventive measures will be found and used. This work further increased my optimism. Of course, this is an initial study, and this is only one of the potential means in the therapeutic, preventive and hygienic arsenal. More research and confirmation will be needed. Yet, even at this stage, the clear positive result of this study shows that it is indeed possible to improve the outcomes for COVID-19 patients even in severe conditions. Moreover, it gives more hope that effective treatments can be sought and found also for other aging-related infectious diseases and conditions.

Q: Is there an explanation regarding the reasons why Covid-19 seems to “pardon” children and affects the most elder individuals, especially men?

A: There is yet no clear or fully agreed explanation. But a plausible cause may be due to the so called “immuno-senescence” phenomenon, or the inability of the aging immune system to cope with new threats and restore the immune balance following the infection. In men the immuno-senescence effects are often more strongly present than in women. Thus, aging appears to be the main risk factor for this disease and if we really wish to defeat this epidemic, we need to address this main risk factor, in other words, we need to therapeutically intervene and ameliorate the degenerative aging process. The proposed mesenchymal stem cell therapy shows the so-called “immuno-modulation” effects or the ability to generally improve the immune system, help restore the immune balance after disturbances, especially for the elderly. And this can be the more general explanation for its effects against the aging-related COVID-19 pneumonia, as well as potentially other aging-related diseases.

Q: How did you manage to find so fast a treatment that is responding so well?

A: The mesenchymal stem cell treatment has been researched and developed by Dr. Zhao and his team for many years, and indicated positive effects for multiple health conditions. It is exactly because of the common and critical role of the immune system impairment in all these conditions, that the treatment developed by Dr. Zhao’s team was already in place and could be immediately used also for this condition dependent on the immune function. Moreover, the success of this therapy against COVID-19 can further boost the research and therapy of other immunity-dependent health conditions and diseases, especially aging-related diseases, due to the common mechanisms of action.

Q: How may this discovery change the game?

A: Unlike other public health measures, like quarantine and hygiene, that can be very quickly applied, the research, development, regulatory approval and application of new therapies is a much slower process. So we should first of all apply the public health measures to contain the epidemic. But the hope is that this therapy will undergo further research and validation as soon as possible, and in case of validated efficacy and safety, will be used in as many patients who need it as possible, as soon as possible. That is exactly why we need to accelerate the research, development and application of promising new therapies. When the new therapy enters wide clinical practice, there are grounds to believe it can improve the health and even save the lives of many patients, not only suffering from COVID-19, but also other conditions.

Q: Which was the response/reaction of authorities after you published the results of your research?

A: The outreach to the authorities in several countries has only started. Moreover, the study is only initial and it is too early to make policy recommendations. A larger validation study is required. Yet, if there is even a slight possibility this could become a life-saving therapy for COVID-19 patients and others, this opportunity should not be missed by the decision makers.

Q: Some treatments are more expensive than others. Will the treatment you discovered be accessible to people, or the cost for producing it will limit its accessibility? 

A: The cells for this treatment can be mass produced and can be rather affordable. Of course, the actual price will depend both on the scale of production and pricing policies. And this is already a question that goes beyond pure technology, but becomes a question about the social means to make new therapies available to all. This should also be a crucial part of the public discussion about the social need to promote the rapid research and development as well as broad application of new therapies that are proven to be safe and effective.

Q: Which are the best measures a country can take to limit the spread and the consequences of the novel coronavirus?

The usual quarantine and public hygiene measures are the most feasible and effective: minimization of large gatherings, minimization of travel, cleanliness. We should hope and work for new effective therapies to arrive as soon as possible. But so far public health measures are the most effective and feasible.