{"id":297,"date":"2014-10-13T20:09:12","date_gmt":"2014-10-13T20:09:12","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=297"},"modified":"2014-10-13T20:09:12","modified_gmt":"2014-10-13T20:09:12","slug":"lithium-for-life-extension","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2014\/10\/13\/lithium-for-life-extension\/","title":{"rendered":"Lithium for Life Extension?"},"content":{"rendered":"

Last month, Anna Fels wrote in the Sunday NYTimes<\/a> suggesting that lithium be added to the drinking water because trace amounts of lithium are associated with lower rates of mental illness, violence and suicide in particular. \u00a0What she didn\u2019t say was that communities with naturally-occurring lithium in their drinking water enjoy greater longevity as well. \u00a0Though the evidence is still thin, there is a credible mechanism, through inhibition of a chemical signal called GSK-3\u03b2. \u00a0The dosages we\u2019re talking about are \u00bd to 2 mg per day, which is less than 1% of the dosage typically prescribed for bipolar disease.<\/em><\/p>\n

\n

 <\/p>\n

Lithium is not a drug, but a chemical element. \u00a0It is right above sodium in the periodic table, and the theory is that the body can\u2019t tell the two apart. \u00a0Sodium is an essential electrolyte, and the body uses it everywhere. \u00a0Nerve signals are propagated as waves of substitution of sodium for potassium. \u00a0The theory is that trace amounts of lithium in the body replace sodium, and move a little faster across membranes, because the ions are smaller and lighter.<\/p>\n

The only study<\/a> looking at all-cause mortality compared different regions of Japan. \u00a0Drinking water was analyzed and mortality rates were compared in 18 different towns, 1.2 million people in all.<\/p>\n

 <\/p>\n

\"\"
Top graph: 18 Japanese towns Bottom graph: Survival curve of lab worms<\/figcaption><\/figure>\n

The top graph shows about 10% decrease in mortality in regions of Japan that had naturally high concentrations of lithium. \u00a0Large dots correspond to counties with large populations. Note the log scale on the X axis; the high counties had about 30 times as much lithium in their drinking water compared to the low counties. \u00a010% decrease in mortality corresponds to about an extra year of life, extrapolating boldly.<\/p>\n

The bottom graph is a survival curve for lab worms with lithium added to their medium, compared to control worms without.<\/p>\n

The most abundant and compelling data is about suicide and violent crime rates in towns with varying amounts of natural lithium in the water. \u00a0\u00a0Twenty different studies in different parts of the world are summarized here<\/a>. \u00a0This same review covers four studies in which lithium was used to treat Alzheimer\u2019s Disease, and all four found benefits, measured by cognitve performance.<\/p>\n

\u00a0<\/strong><\/strong><\/p>\n

Lithium in the diet<\/b><\/p>\n

There is general agreement that animal grazers don\u2019t concentrate lithium, and the best dietary sources are plants. \u00a0Which plants are best? \u00a0The answer seems to depend on lithium in the soil at the site where the plants happen to be grown. \u00a0We can\u2019t characterize some foods as \u201cgood sources of lithium\u201d except according to the location in which they were grown. \u00a0So it is impractical to figure out how much lithium you\u2019re getting in your diet. \u00a0A blood test might be helpful, with the qualification that lithium passes quickly through the body (swept through with sodium), so the test is sensitive to what you happen to have eaten in the last 24 hours.<\/p>\n

\u00a0<\/strong><\/strong><\/p>\n

How does it work?<\/b><\/p>\n

Of course, we don\u2019t know how lithium works, but speculation all centers around a powerful and ubiquitous (if little-known) chemical signal called GSK-3\u03b2. \u00a0Lithium suppresses the action of GSK-3\u03b2. \u00a0All that I know about GSK-3 (alpha and beta forms) I learned from this article by James P Watson<\/a> (not to be confused with the Watson who got the Nobel for DNA).<\/p>\n

The alpha and beta forms of GSK-3 are distinct proteins, derived from separate genes. \u00a0The nomenclature would lead you to believe that they are different forms of the same thing, but the nomenclature is deceptive. \u00a0I\u2019m not going to tell you what GSK stands for, except that the last word is kinase<\/a>, because the name reflects only the particular circumstances in which GSK happened to have been discovered (in 1980).<\/p>\n

If \u201cenergy is the currency of the body,\u201d then phosphate groups are the dollar bills. \u00a0Kinases are enzymes that activate other chemicals by attaching a phosphate group to them. \u00a0The GSK-3s are kinase amplifiers. \u00a0They specialize in finding placs where there is already a single phosphate, then adding more to fully activate the substrate.<\/p>\n

GSK-3\u03b2 has been implicated in the formation of amyloid plaques in the brain, which is one theory for the cause of Alzheimer\u2019s Disease. \u00a0This was the motivation for trials of lithium against AD, which have shown early signs of success.<\/p>\n

The two forms of GSK-3 are involved in many different processes, turning on dozens of genes and turning off dozens more. \u00a0The actions are varied and complex, and GSK-3 cannot be characterized as helpful or harmful. \u00a0Watson refers to GSK-3\u03b1 as the \u201cmainly good guy\u201d and GSK-3\u03b2 as the \u201cmainly bad guy\u201d. \u00a0GSK-3\u03b2 expression increases with age, and it may play a predominantly pro-aging role. \u00a0Suppressing it a bit seems to do some good. \u00a0GSK-3\u03b1 does not modulate consistently with age, either up or down. \u00a0However, when the GSK-3\u03b1 gene is knocked down in mice, the mice are not only viable but have lower fat mass and increased insulin sensitivity\u2014harbingers of extended life. \u00a0Watson characterizes GSK-3\u03b1 nevertheless as \u201cmainly good\u201d based on its effect dampening three aging targets: mTOR, Wnt and P53. \u00a0P53 controls apoptosis=cell suicide which, I have argued, is on a hair trigger as we age. \u00a0Dialing down apoptosis non-selectively has general benefits for preserving muscle and nerve cells, but it also increases cancer risk. TOR is \u201cTarget Of Rapamycin\u201d. \u00a0Recall that rapamycin is a drug that made headlines three years ago when it was found to extend mouse life span, though fed to the mice late in life. \u00a0Rapamycin is a powerful immune suppressor, and may be too dangerous a drug for general human use, but other drugs that dampen TOR signaling may be promising.<\/p>\n

\u00a0<\/strong><\/strong><\/p>\n

Speculation on the future<\/b><\/p>\n

I am convinced that both forms of GSK-3 are key players in aging and other metabolic functions. \u00a0However, they may not be good targets for anti-aging intervention because they play on both teams (promoting pro- and anti-aging pathways). \u00a0The fact that they need \u201cpriming\u201d\u2014a first phosphorylation by a more specific kinase\u2014indicates that they are not an upstream source of aging. \u00a0We can find better targets.<\/p>\n

Trace doses of lithium might prove to be useful for modestly extending life and protecting against Alzheimer\u2019s. \u00a0I\u2019d like to see studies in mice, and larger epidemiological studies, and then clinical trials if warranted. \u00a0There has been only one epidemiological study. \u00a0It should not be difficult to find some part of the world where people don\u2019t tend to move very often and then correlate local concentrations of lithium in drinking water with local variations in age at death.<\/p>\n

 <\/p>\n

For early adopters<\/b><\/p>\n

If you want to experiment with lithium, I think that doses up to 1mg\/day are safe. \u00a0Just for context, this is a tiny quantity. \u00a0One ounce of lithium is a lifetime supply. \u00a0Larger doses are not better. \u00a0They are toxic.<\/b><\/p>\n

Lithium is not a standard ingredient in multi-mineral pills. Nor is it a standard blood test.<\/p>\n

Lithium carbonate is available as a prescription drug, in pills that cannot easily be divided into 100 doses. \u00a0If you felt comfortable with the procedure, I suppose you could dissolve a 500mg pill in a pint of water and take it by the teaspoon. \u00a0There are about 100 tsps in a pint. \u00a0Lithium carbonate is about \u2159 lithium. \u00a0You can also get lithium salts from chemical supply houses.<\/p>\n

Google to find on-line sources of supplements with appropriate low doses of organic salts of lithium, like lithium arginate and lithium orotate. \u00a0They are not better or more bio-available than the simple carbonate, just more expensive.<\/p>\n

\n

Thanks for Michael Eaves for pointing me to sources for this article.<\/p>\n","protected":false},"excerpt":{"rendered":"

Last month, Anna Fels wrote in the Sunday NYTimes suggesting that lithium be added to the drinking water because trace amounts of lithium are associated with lower rates of mental illness, violence and suicide in particular. \u00a0What she didn\u2019t say was that communities with naturally-occurring lithium in their drinking water enjoy greater longevity as well. … Read more<\/a><\/p>\n","protected":false},"author":65,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-297","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"yoast_head":"\nLithium for Life Extension? - Josh Mitteldorf<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/scienceblog.com\/joshmitteldorf\/2014\/10\/13\/lithium-for-life-extension\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Lithium for Life Extension?\" \/>\n<meta property=\"og:description\" content=\"Last month, Anna Fels wrote in the Sunday NYTimes suggesting that lithium be added to the drinking water because trace amounts of lithium are associated with lower rates of mental illness, violence and suicide in particular. \u00a0What she didn\u2019t say was that communities with naturally-occurring lithium in their drinking water enjoy greater longevity as well. ... 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The surprising fact that our bodies are genetically programmed to age and to die offers an enormous opportunity for medical intervention. It may be that therapies to slow the progress of aging need not repair or regenerate anything, but only need to interfere with an existing program of self-destruction. Mitteldorf has taught a weekly yoga class for thirty years. He is an advocate for vigorous self care, including exercise, meditation and caloric restriction. After earning a PhD in astrophysicist, Mitteldorf moved to evolutionary biology as a primary field in 1996. He has taught at Harvard, Berkeley, Bryn Mawr, LaSalle and Temple University. He is presently affiliated with MIT as a visiting scholar. In private life, Mitteldorf is an advocate for election integrity as well as public health. He is an avid amateur musician, playing piano in chamber groups, French horn in community orchestras. His two daughters are among the first children adopted from China in the mid-1980s. Much to the surprise of evolutionary biologists, genetic experiments indicate that aging has been selected as an adaptation for its own sake. This poses a conundrum: the impact of aging on individual fitness is wholly negative, so aging must be regarded as a kind of evolutionary altruism. Unlike other forms of evolutionary altruism, aging offers benefits to the community that are weak, and not well focussed on near kin of the altruist. 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The surprising fact that our bodies are genetically programmed to age and to die offers an enormous opportunity for medical intervention. It may be that therapies to slow the progress of aging need not repair or regenerate anything, but only need to interfere with an existing program of self-destruction. Mitteldorf has taught a weekly yoga class for thirty years. He is an advocate for vigorous self care, including exercise, meditation and caloric restriction. After earning a PhD in astrophysicist, Mitteldorf moved to evolutionary biology as a primary field in 1996. He has taught at Harvard, Berkeley, Bryn Mawr, LaSalle and Temple University. He is presently affiliated with MIT as a visiting scholar. In private life, Mitteldorf is an advocate for election integrity as well as public health. He is an avid amateur musician, playing piano in chamber groups, French horn in community orchestras. His two daughters are among the first children adopted from China in the mid-1980s. Much to the surprise of evolutionary biologists, genetic experiments indicate that aging has been selected as an adaptation for its own sake. This poses a conundrum: the impact of aging on individual fitness is wholly negative, so aging must be regarded as a kind of evolutionary altruism. Unlike other forms of evolutionary altruism, aging offers benefits to the community that are weak, and not well focussed on near kin of the altruist. This makes the mechanism challenging to understand and to model. more at http:\/\/mathforum.org\/~josh","sameAs":["http:\/\/AgingAdvice.org"],"url":"https:\/\/scienceblog.com\/joshmitteldorf\/author\/joshmitteldorf\/"}]}},"jetpack_featured_media_url":"","jetpack_shortlink":"https:\/\/wp.me\/pgtN8h-4N","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/posts\/297","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/users\/65"}],"replies":[{"embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/comments?post=297"}],"version-history":[{"count":0,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/posts\/297\/revisions"}],"wp:attachment":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/media?parent=297"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/categories?post=297"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/tags?post=297"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}