Low dose lithium reduces cellular senescence

A recent study shows that low-dose lithium may act as a senolytic.[ref] This has important implications in healthy aging – including preventing mortality from respiratory diseases, such as COVID, and neurodegenerative diseases like Alzheimer’s.

First, let me go into a little background information on lithium and then cellular senescence. Next, I’ll explain the new study on lithium as a senolytic and why this is so cool.

Lithium – naturally occurring mineral:

Lithium is perhaps best known for its use in batteries and as a drug for bipolar disorder.

As a naturally occurring mineral, lithium exists at varying levels in the soil and water throughout the world. According to estimates, people consume about 3mg of lithium a day from food and water, however, the amount varies a lot depending on where your food is grown and the source of your groundwater.

Epidemiological studies show that areas with higher levels of lithium in the groundwater have lower levels of suicide and assaults. Studies also correlate higher levels of lithium in water with lower levels of Alzheimer’s disease. [ref][ref][ref]

Lithium as a drug or supplement:

Lithium carbonate is about 19% elemental lithium. Thus a 300 mg dose prescribed for bipolar disorder would equate to about 57 mg of elemental lithium.

Microdoses of lithium carbonate used in clinical trials for Alzheimer’s disease are in the 300 μg to 30mg range. Elemental lithium would be around 57 μg to 5mg. Still a huge range, but in the ballpark of what a person likely consumes from food, depending on where the food is grown.

Several clinical trials now show that microdoses of lithium may prevent cognitive losses in AD.[ref][ref]

Supplemental lithium orotate is available in 5 mg – 20 mg doses. You can get it on Amazon or through health food stores.

Cellular senescence in aging:

Cellular senescence is a natural process that cells go through when they are at the end of their replicative life. When a cell can no longer replicate safely, it will send out signals for the immune system to destroy the cell. This is a process that occurs throughout life, but in older age, the number of senescent cells multiplies too rapidly for the immune system to keep up.

The signals that a senescent cell gives off are inflammatory cytokines. When all goes according to plan, the inflammatory cytokines cause a quick immune response. But in aging, the accumulated senescent cells give off a lot of inflammatory cytokines, increasing overall inflammation in the body. Uncleared senescent cells can cause harm to their neighboring cells through the signals that the cytokines give off.

Lithium as a senolytic:

The study on low-dose lithium as a senolytic shows that senescent cells treated with low concentrations of lithium decreased the inflammatory cytokines associated with senescence.[ref] The decrease in inflammatory markers included lower levels of IL-6.  Interleukin 6 (IL-6), an inflammatory cytokine, becomes elevated in COVID-19 in patients with severe disease.

The study results showed that the low-dose lithiums is acting via the same mechanism that high-dose amount act: prescription levels of lithium for bipolar disorder inhibits GSK3B activation.

Conclusion:

More research is needed to determine dosages and the mechanism of action of lithium as a senolytic. It is also not clear, to me at least, whether lithium is clearing out senescent cells, as a senolytic does, or if it is suppressing the cytokines from senescent cells.

In light of the recent FDA approval of a $56,000/year Alzheimer’s drug that doesn’t slow or reverse cognitive decline, I would love to see more trials on microdosing lithium for Alzheimer’s disease. The stark difference between a very cheap mineral supplement that does stop cognitive decline in Alzheimer’s patients vs. the horribly expensive drug that does not actually help…well, words fail me on why the government chooses via the FDA to pay for (via Medicare) a drug that is 1,000 times more expensive and yet less effective.

I would also love to see clinical trials on lithium as a senolytic in elderly people. Other senolytics, such as quercetin, fisetin, luteolin, and dasatinib, have shown efficacy in diseases related to senescence.[ref][ref] Lithium would be an even less expensive, readily available choice – if it is as effective as other senolytics.