Melatonin, mitochondria, and dermal aging

Melatonin is a hormone involved in regulation of sleep and the circadian rhythm, as well as the immune system. The molecule has also been demonstrated to have a positive effect on lifespan in some rodent model systems, though it is unclear whether this is due to receptor-mediated functions or can instead be ascribed to its potent antioxidant activity.

A recent study by Eşrefoğlu et al. demonstrates that supplemental melatonin slows age-related deterioration, including severe mitochondrial dystrophy, in the skin of pinealectomized rats (the pineal gland is the site of melatonin production):

… The present study was aimed to determine the fine structure of the abdominal and thoracic skin in pinealectomized rats and the effect of melatonin on skin ultrastructure. Rats were pinealectomized or sham operated (control) for 6 months. Half of the pinealectomized rats were treated with 4 mg/kg melatonin during the last month of the experiment. Pinealectomy resulted in prominent ultrastructural changes in the skin. Epidermal atrophy, disorganization and cytological atypia were obvious. Tonofilament distribution was not uniform, and intercellular space was narrow. Nuclear irregularity and heterochromatin condensation were detected. Many mitochondria were irregular and edematous with increased translucence of the matrix, either partial or total destruction of crests and frequently the presence of vacuoles, myelin figures and dense bodies. … The epidermis in melatonin administered pinealectomized rats was obviously thicker than that of pinealectomized rats. The cells of each layers had characteristic morphological and ultrastructural features. Nuclear irregularity and heterochromatin condensation were not seen. Mitochondria were generally normal in ultrastructural appearance but rarely vacuoles and myelin figures were observed. … This paper provides an additional ultrastructural evidence that the damage to mitochondria is the major contributory factor to skin aging and that melatonin has potent therapeutic effects in reducing age-related changes via protecting fine structure of the skin.

While the system may seem a little bit artificial (an major hormone-producing gland has been removed), I think the logic is sound: Pinealectomized rats undergo premature skin aging, implying that some product of the pineal is working to prevent skin aging in an unmolested rat. Adding back melatonin alone (of all the many hormones now absent) prevents this premature aging completely, implying that melatonin is the relevant pineal product.

One alternative interpretation is that the pineal produces some other product that prevents skin aging, but that the mechanism of skin aging is primarily oxidative, so that the truly gigantic doses of melatonin used here (4 mg/kg, or ~300 mg for a human adult; by comparison, the over-the-counter pills one can buy to help with jetlag or sleep disorders are 1 to 3 mg each) are acting via the compound’s antioxidant properties rather than its receptor-mediated functions.

An open question is whether supplemental melatonin will slow or prevent dermal aging in animals with intact pineal glands. The levels of melatonin produced at night do decrease with age, so it’s possible that at some point in the lifespan the hormone is present at insufficient levels to prevent the cellular damage described here. If that happens before other forces have wreaked havoc, and can therefore be considered a primary cause of early age-related decline in skin cells, then supplementation should be a good strategy for extending the healthy functionality of the body’s largest organ.

Something to think about. I’ll sleep on it.



  1. I have a genetic collagen disorder and have found darkness (and associated melatonin) very helpful, as I’ve noted at

    There’s also good evidence that the opposite, aldosterone, interferes with proper collagen formation, as noted there.

  2. I’m always looking for anti-aging research, so I’m glad to find this. At least one study has shown that the physiologic dose for melatonin in humans is 0.3mg – even less than the over the counter doses generally see. And that taking more actually can impair sleep – so this does not look too promising as an extra supplement, but the more we learn about how we function, the better.

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