Microdose lithium reduces cellular senescence in human astrocytes - a potential pharmacotherapy for COVID-19?

Tania Viel,Anand Rane,Julie Andersen,Shankar Chinta,Hudson Buck,Manish Chamoli

doi:10.18632/aging.103449

Abstract

Cell senescence is a process that causes growth arrest and the release of a senescence associated secretory phenotype (SASP), characterized by secretion of chemokines, cytokines, cell growth factors and metalloproteases, leading to a tissue condition that may precipitate cancers and neurodegenerative processes. With the recent pandemic of coronavirus, senolytic drugs are being considered as possible therapeutic tools to reduce the virulence of SARS-CoV-2. In the last few years, our research group showed that lithium carbonate at microdose levels was able to stabilize memory and change neuropathological characteristics of Alzheimer’s disease (AD). In the present work, we present evidence that low-dose lithium can reduce the SASP of human iPSCs-derived astrocytes following acute treatment, suggesting that microdose lithium could protect cells from senescence and development of aging-related conditions. With the present findings, a perspective of the potential use of low-dose lithium in old patients from the “high risk group” for COVID-19 (with hypertension, diabetes and chronic obstructive pulmonary disease) is presented.

Highlights

Since the beginning of the coronaviral burst in December 2019, SARS-CoV-2 has widely spread in more than 50 countries around the world
The aging process is characterized by increased levels of oxidative stress and chronic inflammation contributing to many age-related pathologies [2, 3]
It has been suggested that increases in inflammation may be promoted by the release of pro-inflammatory and other factors from senescent cells as part of what is known as the senescence-associated secreted phenotypes (SASP) [4, 5], which includes increase in senescence-associated β-galactosidase (SA-β-gal) activity, increased levels of the cyclin-dependent kinase (CDK) inhibitors p16 and p21, and pro-inflammatory cytokines including IL-6, IL-8 and IL-1α [6]

Summary

INTRODUCTION

Since the beginning of the coronaviral burst in December 2019, SARS-CoV-2 has widely spread in more than 50 countries around the world. In a recent research perspective, the use of senolytic drugs was suggested for the treatment and prevention of COVID-19 [10] These drugs induce the apoptosis of senescent cells and reduce production of the SASP, reducing vulnerability to chronic diseases [11]. We observed that low dose of Li2CO3 including 2.5 μM, 10 μM and 25 μM significantly suppressed amyloid-β (Aβ) increased SA β-gal staining in astrocytes, a hallmark of cellular senescence (Figure 1I, 1J). The fact that microdose lithium suppresses IL-6 and recent finding correlating IL-6 level with severity of the diseases in COVID-19 patients provides a strong rationale for why lithium treatment should be tested as treatment In this way, low-dose lithium may constitute a novel potential therapeutic to reduce the virulence of SARS-CoV-2. It is important to highlight that no side effects were verified in old people with the use of low-dose lithium [12, 26]

MATERIALS AND METHODS

Findings

Data availability statement