I’ve heard again and again about how the reason that older people are more impacted by Covid19 is due to their diminished immune system capacity. This seemed from the start to make little sense to me. I mean, if their immune systems were degraded, they’d have less acute inflammation as a result of infection, not more. Now I believe that the real reason is not that their immune system diminishes, but rather that their antioxidant defenses drop as they get older.
Studies have shown that there are statistically significant decreases of Zn,Cu-superoxide dismutase (SOD-1), catalase (CAT), and glutathione peroxidase (GSH-Px) activities in elderly people in comparison with the control group. Moreover there is an inverse correlation between the activities of SOD-1, CAT, and GSH-Px and the age of the examined persons. (https://doi.org/10.2147/CIA.S201250)
Why would this matter?
TMPRSS2.
Both the SARS coronavirus of 2003 and the novel coronavirus of 2019/20 are activated by TMPRSS2 and can thus be blocked by TMPRSS2 inhibitors. SARSCoV2 uses ACE2 as a receptor for entry and its spike protein is primed by TMPRSS2. Cells expressing TMPRSS2 show increased activation and replication of SARS-CoV. As an aside, TMPRSS2 is known be up-regulated by androgenic hormones, a possible explanation why Covid19 is more common and more severe in men.
Sprouts and green tea.
Sulforaphane is a natural plant compound found in many cruciferous vegetables like broccoli, cabbage, cauliflower, and kale; it has been shown to block TMPRSS2. From the article below:
‘Antioxidants, such as sulforaphane (SFN) dampens inflammation, alleviates oxidative stress, and alters the protease/ antiprotease balance.’
‘Furthermore, we and others have shown that SFN decreases TMPRSS2 expression, which we speculate is mediating the SFN-dependent protection against influenza.’
‘Indeed, our studies indicate that SFN is protective against respiratory viruses such as IAV. We have shown that SFN decreases IAV replication by reducing IAV entry into respiratory epithelial cells.’
‘Furthermore, our group recently showed that sulforaphane-containing broccoli sprouts significantly decreased IL-6 and markers of viral replication in nasal lavage fluid from smokers in subjects inoculated with the live attenuated influenza virus vaccine.’
Green tea EGCG also reduced TMPRSS2 secretion, and decreased influenza replication.
BTW, this would also explain why the very young seem less impacted by Covid19: they have premium antioxidant defenses. Not only are their antioxidant levels higher, but they also work much better. On the other hand, many of the co-morbidities that seem to increase the odds of severe infection (smoking, diabetes, respiratory illness, etc) are also know to be associated with low SOD and catalase levels.
There are other agents that may also have activity, principally those that enhance the major internal antioxidant cycle that uses NFE2L2 (NRF2) via KEAP1.
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