Giving away electrons might be the mechanism for both longevity as well as usefulness in battery industry.

1. LONGEVITY AND LITHIUM BATTERIES
Much has been written about lithium and its influence on GSK-3, Bcl-2, phosphatase, etc, but the role of lithium on mitochondrial
electron transport, has only became clearer recently. It seems that this precise action of lithium renders it a veritable anti- aging
drug.
Lithium is a metal that easily gives away electrons. For this reason it is used in the production of batteries. Another atom that
donates electrons easily is hydrogen.
Oxidizers accept electrons and reducers give electrons away.
This unique property of lithium makes it invaluable for biological systems as well. Lithium is a reducer( an electron pump). Other
reducers such as hydrogen are part of cellular redox systems. When lithium gives an electron away it becomes oxidized..
The mitochondrion is a biological battery. Its charge comes from the difference of potential between inner and outer
mitochondrial membrane. What we call respiratory chain is a biological system meant to separate electrons from their atoms,
thus pumping electrons on one side of a membrane, while protons are left on the other side, creating a charge(polarization).
Unlike our batteries, the mitochondrion uses hydrogen. The reason we are not using hydrogen in making batteries is because of
safety( nickel hydrogen batteries are being used in satellites, because of their long life).
In the mitochondrial electron transport chain electrons move from an electron donor (NADH or QH2) to a terminal electron
acceptor (oxygen) via a series of redox reactions. The resulting transmembrane proton gradient is used to make ATP via ATP
synthase ( oxidative phosphorylation). This is called the chemiosmotic coupling hypothesis which was proposed by Peter D.
Mitchell (Nobel Prize in chemistry). Electron transport chain and oxidative phosphoylation are coupled by a proton gradient
across the inner mitochondrial membrane.

2. The efflux of protons from the mitochondrial matrix creates an electrochemical gradient. This gradient is used by the
ATP synthase complex to make ATP (energy).
LITHIUM AND BRAIN ENERGY
Recent studies show that lithium enhances mitochondrial oxidative phosphoylation in human brain by stimulating mitochondrial
respiratory chain enzyme activities. Lithium's effect on the mitochondrial respiratory chain presents further evidence of the
pathophysiological significance of mitochondrial dysfunction in bipolar disorder. ( Lithium-induced enhancement of
mitochondrial oxidative phosphorylation in human brain tissue; Department of Psychiatry, CCM, University of Berlin,
Universitätsmedizin-Charité, Elisabethkirchstrasse 5, 10115 Berlin, Germany. iris.maurer@charite.de.).
The common denominator between batteries and mitochondrial oxidative phosphorylation is the
propensity of lithium to donate electrons easily.
LITHIUM AND LONGEVITY
Professor Dr. Michael Ristow's team along with Japanese colleagues from universities in Oita and Hiroshima have
demonstrated by two independent approaches that even a low concentration of lithium leads to an increased life
expectancy in humans as well as in a model organism, the roundworm Caenorhabditis elegans.
The research team presents its results in the online edition of the scientific publication European Journal of Nutrition.
In another study nematode worms treated with lithium showed an astonishing 46 percent increase in lifespan, raising
the question of whether humans taking lithium are also taking an anti-aging medication. Conducted by the Buck
Institute, the study results were published in the Journal of Biological Chemistry.
By helping the mitochondrion in the brain, heart and muscle with oxidative phosphorylation makes lithium an anti-aging
medication. The mechanism of lithium’s action on longevity is different than that of sirtuins (resveratrol).

3. ANOTHER MECHANISM FOR LITHIUM’s ANTI-AGING ACTION
On the outer mitochondrial membrane there are two kinds of proteins. One group facilitates mitochondrial damage (such as
BAX). The other group facilitates mitochondrial repair (such as Bcl-2).
Bax protein damages the mitochondrion by perforating the outer membrane, forming pores. Bcl-2 protein protects the
mitochondrial outer membrane by patching these pores.
Bcl-2 gene family codes for both groups of pro-survival and pro-apoptotic proteins.
Bcl-2 is a family of genes that produce both pro-survival and pro-apoptotic proteins. BAX is a death-promoting (pro-
apoptotic) protein that inflicts damage (open pores) to the outer mitochondrial membrane.
Bcl-X and Bcl-2 genes produces proteins that are able to patch the pores of the outer mitochondrial membrane, thus
evading apoptosis.

4. Bax protein is like a woodpecker, it literally drills holes into the mitochondrial outer membrane, leading to the formation
of pores. Enzymes from the mitochondrial matrix and citochrome C pour out through the pores, activate caspases .
Recent studies revealed that lithium increases Bcl-2 expression and has a prominent role against excitotoxicity. One
of the studies was published in Journal of Biological Chemistry, by Ren-Wu and De-Chuang. (Long Term Lithium
Treatment Suppresses p53 and Bax Expression but Increases Bcl-2 Expression).
It seems that there are many mechanisms by which lithium increases longevity, but ultimately they may be due to its
unique ability of giving away its electrons.
ADONIS SFERA, MD