A Perspective on the Proposed Association of Melatonin and Aging

Summary: Melatonin is another substance that we need more data on but doesn't look all that promising.

Interestingness: 1

Paper by Russel J Reiter, Dun-Xian Tan, Seok Joong Kim, Javier Cabrera and Daniele D'Arpa in the Journal of Anti-Aging Medicine, Volume 1, Issue 3, Fall 1998.

(((Melatonin is a molecule produced by the pineal gland that regulates the circadian rhythm. It puts you to sleep. It gets produced in the darkness, and bright light interrupts its production)))

Melatonin is another hormone which the body produces less of as it gets older. A graph with a linear best fit seems to indicate that peak melatonin concentration drops by about half between the ages of 20 and 70, although the text mentions a pronounced drop between the ages of 40 and 60. It also mentions factor of two differences between young people of the same age (((which makes it a bit less important in my eyes))). Production of melatonin in calorie-restricted rats drops slower than in normal rats (((probably more of an endorsement of calorie restriction as a method to slow aging than support for melatonin being important in the process)))

(((The paper now switches to melatonin as an anti-oxidant, which doesn't interest me much))) Melatonin mops up hydroxy radicals, peroxyl radicals, and neutralises single oxygen atoms and peroxynitrite anions (ONOO-). It also stimulates activity glutathione peroxidase and glutathione reductase (((dunno how))) which neutralise hydrogen peroxide. The paper stresses the effectiveness in protecting against lipid peroxidation.

Switching to direct aging studies, it mentions a study where the pineal glands of young rats were transplanted into old rats and these older rats were judged to have become younger, a result which the authors of this paper say is hard to accept since the pineal gland stops producing melatonin after the nerves are destroyed (((edit: the author of that paper seemed unhappy with these comments on this paper, and wrote to the editor in the next issue. They do not think the effect is mediated by restoring melatonin levels. Maybe I'll read their paper))) (((edit 2: paper seems reasonable. Part of it is the drugging of the water with interesting results. The pineal transplantations are into the other mice's (not rats) thymus, because they are supposedly similar tissue. Tiny samples, 15 mice transplanted with pineal glands total, but quite a strong effect (810 days vs 747 days mean survival on mice operated on in the 20th month). Probably completely unrelated to melatonin though.))) (((For reference, other paper is "Pineal Control of Aging: Effect of melatonin and pineal grafting on aging mice" by Walter Pierpaoli and William Regelson)))

Studies of long term melatonin administration in rats have had inconclusive results. Drugging the drinking water extended lifespan when it was given during the night but not during the day. Injecting melatonin directly extended lifespan when done in the morning, but not in the afternoon. (((These studies were done on groups of 10 and 15 mice respectively. The second one focuses on the effect of injections of lithium chloride, and melatonin has no effect on top of lithium chloride. The effects look sort of interesting to me, but this paper doesn't think much of them)))



Abstract follows:

Melatonin, the chief secretory product of the pineal gland, has been proposed to have some functional association with aging. Certainly, melatonin production in vertebrates, including humans, wanes with increasing age. This age-related drop in melatonin has been inferred to be consequential in terms of accelerating some aspects of aging, although the experimental evidence for this is not compelling at this point. There are several functional aspects of melatonin that make it of interest to gerontologists. Thus, the cyclic production of melatonin is reflective of the biological clock, and circadian disturbances in general are a feature of aging. These alterations may impact the rate of aging. Also, melatonin is an antioxidant and, as such, it reduces free radical damage. A primary theory of aging is accumulated oxidative damage, and any molecule, such as melatonin, that retards the accumulation of that molecular damage may forestall some aging processes. The experimental data are incomplete, however, and the specific association of the diminished melatonin cycle with aging or age-related diseases remains suggestive but unproven.