Thyrotropin-Releasing Hormone Accelerates and Enhances the Age-Postponing Effects of Melatonin

Summary: Thyrotropin-releasing hormone (TRH) plus melatonin increase lifespan of old mice by three months

Interestingness: 4

Paper by Walter Pierpaoli, Daniele Bulian, Gordana Bulian and Gonzague Kistler in the Journal of Anti-Aging Medicine, Volume 2, Issue 4, Winter 1999.

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The sample size is small, 15 mice per group, but the effect size is interesting. The main table of results shows the following: for four groups of 15+-1 BALB/cJ female mice, 20 months old at the start of the experiment, a control group, one given melatonin, one TRH, one both, mean survival was 765+-54 days, 810+-50 days, 804+-80 days, and 861+-70 days respectively. There's also other results, with the TRH plus melatonin combination raising numbers of leukocytes and blood lymphocytes, and lowering cholesterol and triglycerides in old mice.

TRH induces release of thyrotropin, aka thyroid-stimulating hormone (TSH) which then induces the thyroid to release T3 and T4. Wikipedia has TRH being produced in the hypothalamus but the paper says it's produced by the hypothalamus and the pineal gland.

The mechanism behind this isn't precisely hypothesised but they do mention immune system upregulation. The authors hype TRH as the real reason for the supposed effects of melatonin on aging, saying that melatonin dosing stops the pineal gland making its own, so it can stay young and keep on making TRH later. TRH is also given as the explanation of why pineal gland transplantation from young to old mice, mentioned in http://readingrejuvenationresearch.blogspot.com/2010/03/perspective-on-proposed-association-of.html, increases the longevity of those mice.

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Abstract follows:

Studies over a period of several years have suggested an age-postponing effect of circadian nocturnal administration of melatonin and of young-to-old pineal grafting in rodents. Of the two procedures, the effect of pineal grafting was significantly more pronounced. Also, old-to-young and young-to-old pineal transplantation in normal or pinealectomized recipients suggested that the pineal itself contains the capacity to prevent or to accelerate the course of aging depending on the age of the donor and/or of a recipient when the pineal is transplanted. This observation prompted the idea that the "program of aging" might be governed by the capacity of the pineal to maintain the control of central neuroendocrine functions and to constantly synchronize the synthesis and release of hormones according to a strict circadian periodicity and seasonal rhythmicity. This report deals with the experimental evidence that, while melatonin alone exerts a low-level age-postponing activity, its age-delaying effects are greatly enhanced and accelerated when given in combination with a pineal peptide, thyrotropin-releasing hormone (TRH). This peptide may be a key element in the mechanism by which both melatonin and pineal grafting might postpone aging. In fact, as suggested by our data here, TRH could be one of the basic mediators in the brain (pineal-hypothalamic-hypophyseal axis) and in peripheral endocrine glands (e.g., the beta, insulin-producing cells in the pancreas). TRH may directly translate the light and temperature-mediated environmental stimuli into rapid energy-adapting biochemical processes which constantly monitor cell functions relating to energy production, in particular those required for thermoregulation. We show here that this energy-monitoring action of TRH is not thyroid mediated. We also show that TRH is not itself a toxic agent even when administered daily for long periods at a very high pharmacological dosage.