A geroscience perspective on immune resilience and infectious diseases: a potential case for metformin

Abstract

We are in the midst of the global pandemic. Though acute respiratory coronavirus (SARS-COV2) that leads to COVID-19 infects people of all ages, severe symptoms and mortality occur disproportionately in older adults. Geroscience interventions that target biological aging could decrease risk across multiple age-related diseases and improve outcomes in response to infectious disease. This offers hope for a new hostdirected therapeutic approach that could (i) improve outcomes following exposure or shorten treatment regimens; (ii) reduce the chronic pathology associated with the infectious disease and subsequent comorbidity, frailty, and disability; and (iii) promote development of immunological memory that protects against relapse or improves response to vaccination. We review the possibility of this approach by examining available evidence in metformin: a generic drug with a proven safety record that will be used in a large-scale multicenter clinical trial. Though rigorous translational research and clinical trials are needed to test this empirically, metformin may improve host immune defenses and confer protection against long-term health consequences of infectious disease, age-related chronic diseases, and geriatric syndromes.

Outcome and death risk of diabetes patients with Covid-19 receiving pre-hospital and in-hospital metformin therapies

“…Indeed, COVID-19 patients that used metformin showed lower IL-6 levels compared to non-metformin users at admission [ 14 ]. It also may be able to promote an anti-inflammatory response through M2 polarization and decreasing IL-17 and reducing or preventing induction of cytokine storm [ 45 ]. Therefore, the use of metformin may improve clinical features of diabetes patients and reduce risk of inflammatory disease caused by COVID-19.…”

Metformin Protects against Radiation-Induced Acute Effects by Limiting Senescence of Bronchial-Epithelial Cells

“…Metformin was already shown to be able to reduce pro-inflammatory cytokine secretion, particularly Ccl2 [24]. It has been supposed that metformin can limit the onset and duration of a cytokine storm-like responses, particularly upon lung damage thereby preventing excessive lung damage [25][26][27]. For example, metformin efficiently counteracted the lipopolysaccharide-induced inflammatory response within acute lung injury [28,29].…”

Drug delivery systems as immunomodulators for therapy of infectious disease: Relevance to COVID-19

“…Furthermore, metformin, currently used to treat T2D, could be a beneficial therapeutic in COVID-19 treatment. Metformin is known to modulate metabolism [213] and has been suggested to demonstrate benefits such as anti-inflammatory properties as well as reduced mortality [214] , [215] during COVID-19 infection. Metformin is already given as an extended release formulation, however, there are developments for metformin nanoparticles which aid in extended release, lower dose frequencies and improvements of compliance [216] .…”