Senolytics showcase link between life extension and therapeutics
A significant part of ongoing anti-aging research has conventional applications in the treatment of gerontological conditions while also opening up potential avenues for life extension. Two entrepreneurs – Lewis Gruber of Siwa Therapeutics and Marc Ramis Castelltort of Senolytic Therapeutics and Rejuversen AG – discuss how their cutting-edge research serves two purposes – to improve health at old age, and to move one step closer to the dream of vastly expanded human longevity.
Over the past three to four decades, scientists have refined their understanding of cellular aging processes and their effects, in terms both of specific pathologies and of the overall biological aging of the body. These insights have opened up ways to treatments that may one day help us achieve vastly extended health- and lifespans simultaneously. Indeed, among the potentially life-extending interventions that companies are actively researching today, there are many approaches that could not only help us live longer, but could also pave the way for new cures for specific illnesses and conditions that are currently untreatable. Given the close overlap between clinical therapeutics for diseases and life extension research, some even argue that “aging” should be considered a condition in its own right.
A glance at companies’ portfolios confirms this nexus between life extension and disease treatment. There is no firewall between longevity research and conventional medical R&D. A prime example is the field of cellular senescence, in which researchers use senolytic compounds to try and kill off “zombie” cells that have reached Hayflick’s Limit and stopped dividing due to shortening of telomeres. These senescent cells emit cytokines that cause inflammation and immune cell activation in the surrounding tissue and can even induce senescence in healthy cells. Cytokines are especially important in regulating the immune response, and research on immunosenescence ties in with more general efforts to understand the functioning and eventual dysfunction of the immune system, which have gained urgency in connection with the COVID-19 pandemic.
COVID-19 research: full speed ahead
“Although the pandemic has caused a slowdown in many areas, any solutions that are potentially effective in stopping the coronavirus will of course be fast-tracked,” said Lewis Gruber, CEO and co-founder of Siwa Therapeutics, in a recent interview with Supertrends. This biopharmaceutical company, based in Chicago, USA, has developed a humanized monoclonal antibody, SIWA 318H, which it hopes can directly target cells affected by viruses, including COVID-19. The antibody seeks out cells that have an abnormally high level of glycolysis and oxidative stress. Among these are cancerous, senescent, and virally infected cells.
“By removing those cells, we eliminate deleterious [damaging] secretions and stimulate regenerative processes,” Gruber explains. While the company remains focused on aggressive cancers, the devastation wreaked by COVID-19 has prompted Siwa Therapeutics to test its antibody as a potential treatment for infectious diseases and related cytokine storms and as a potential building block for a vaccine against the novel coronavirus.
Expanding lifespans – and health-spans
Another company that concentrates on the removal of senescent cells is Senolytic Therapeutics, a Barcelona-based biotech firm seeking to develop novel medicines and drugs for life extension and health improvement while also offering consulting services to other firms in the biotech sphere. The company’s co-founder, Marc Ramis Castelltort, noted in an interview with Supertrends that the main focus for now is on conventional life extension: “We are developing senolytic-based drugs that can treat diseases including fibrosis and certain forms of cancer. To the extent that such therapies can help people live longer, we are also expanding their lifespans, but our main goal for now is the treatment of pathologies that are associated with the biology of aging.” With support from the EU’s Horizon 2020 research and innovation program, the company hopes to come up with new medicines to combat fibrotic diseases and other age-related disorders.
Nevertheless, the insights that Castelltort and his team have gained into cellular aging and the role of senescent cells as a cause of frailty in old people have prompted him to found a second company, Rejuversen AG, which hopes to find cures for therapy-induced senescence in the field of oncology. “We aim to be able to present our first clinical trial by 2023,” he says.
“Although we are still at the discovery stage, we are confident that we will soon be able to treat aging-associated diseases and thus extend not only our lifespans, but also our ‘health-spans” (Marc Ramis Castelltort)
The best approach to do this, according to Castelltort, is to treat age-related diseases first and then life extension as two sides of the same coin.
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