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

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.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and glial cells: Insights and perspectives

“…Thus, this data together with the fact that glial cell dysfunctions are highly associated with aging and neurodegenerative diseases ( Diniz et al., 2017 , 2019 ) highlight the need to consider the long-term consequences of glial activation and neuroinflammation triggered by SARS-CoV-2 . Interestingly, recently, Viel and colleagues showed that low-dose of lithium suppresses IL-6 and reduces SASP (senescence-associated secretory phenotype) in senescent human astrocytes, suggesting that is a potential therapeutic strategy to COVID-19 in elderly patients ( Viel et al., 2020 ).…”

Telomere Length and Oxidative Stress and Its Relation with Metabolic Syndrome Components in the Aging

“…The research on such molecules has been growing in recent years, and therefore, the association between senolytics and senomorphics with other age-related diseases has come to light. Regarding the latter, it has been observed that the acute administration of lithium carbonate is able to reduce the SASP of human astrocyte-derived induced pluripotent stem cells (iPSCs) [ 75 ]. In addition to the above, the administration of this compound is also involved in telomere length dynamics, since chronic treatment in a triple transgenic experimental model of Alzheimer’s disease increases TL in the hippocampus and parietal cortex in a tissue-specific manner [ 76 ].…”

Impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the Nervous System: Implications of COVID-19 in Neurodegeneration

“…Senescent cells, characterized by sustained cell cycle arrest and the production of a distinct senescence-associated secretory phenotype (SASP), such as cytokines and chemokines ( 90 , 91 ), are commonly detected in neurodegenerative diseases. A study suggested the use of lithium, as a senolytic agent, to selectively induce apoptosis of senescent cells, as a potentially therapy to treat COVID-19 positive patients ( 92 ). They reported that low doses of lithium decreased the release of IL-6 and IL-8 and suppressed amyloid-β (Aβ) increased SA β-gal staining in induced pluripotent stem cells (iPSCs)-derived astrocytes, all hallmarks of cellular senescence.…”