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Life Extension Magazine

LE Magazine December 1995

Melatonin Extends Lifespan

The sine qua non of anti-aging research is the ability of a therapy to extend maximum lifespan in animals. (It's not practical to study this in humans.) In this respect, melatonin is highly promising, but the lifespan studies conducted with melatonin to date have been few and have been limited in size. As a result, the findings of these studies are far from definitive. They leave certain questions unanswered, the resolution of which will require future research.

Joint Lifespan Studies

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Melatonin lifespan studies have been conducted in three different strains of mice as a joint venture of Walter Pierpaoli of the University of Ancona in Italy and William Regelson of Virginia Commonwealth University in Richmond. Drs. Pierpaoli and Regelson have written a recently published book entitled "The Miracle Of Melatonin" (Simon and Schuster, 1995) in which they describe these experiments. The results were published in their scientific paper:

"Pineal control of aging: Effect of melatonin and pineal grafting on aging mice" in the Proceedings of the National Academy Of Sciences, USA, Vol. 91, pp. 787-791, January 1994.

Two Types Of Experiments

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In these experiments, aging mice were given melatonin in their drinking water during a fixed circadian dark cycle, when melatonin is normally produced.

In a second set of experiments, the pineal gland, which is the body's prime source of melatonin, was transplanted from young (3-4 months) to old (16-22 months) mice.

In the transplant experiments, the pineal gland was not removed in the old mice. The site of the graft in the recipient mice was the thymus gland, which is believed to be similar to the pineal in its embryologic development.

Three strains of mice were used in these studies: BALB/c females; NZB females; and C57BL/6 males, with the pineal transplants performed in the BALB/c and C57BL/6 females as well as in BALB/cJ-C57BL/6 hybrids. In the BALB/6 mice, melatonin administration was started at 15 months of age with 12 experimental animals and 26 controls. In the NZB mice, melatonin was started at 5 months of age, with 10 experimental animals and 10 controls. In the C57BL/6 mice melatonin was started at 19 months of age, with 15 experimental animals and 20 controls.

Results Of Lifespan Studies

The results of these experiments demonstrated both median and maximum lifespan extension in all four experimental groups. There were no significant differences in weight among any of the experimental and control groups, which rules out calorie restriction as the cause of the lifespan extension effects in these studies.

In the BALB/6 mice, the average survival of the control animals was 715 days compared to 843 days in the melatonin-treated mice. The median survival in controls was 23.8 months compared to 28.1 months in the melatonin-treated mice, and maximum survival in the controls was 28 months compared to 31 months in the melatonin animals.

In the NZB mice, maximum survival was 19 months in the control animals compared to 23 months in the melatonin-treated animals. The maximum survival in 10 NZB animals given melatonin during daylight hours was 20 months.

In the C57BL/6 mice, the melatonin-treated animals lived up to 6 months longer than the control animals.

The Pineal Transplants

Pineal glands from young (3-4 months) BALB/cJ female mice were transplanted onto the thymus glands of 3 22-month old BALB/cJ mice. Similar pineal transplants were put into 7 16-month-old C57BL/6 female mice as well as into 5 19-month-old BALB/cJ-C57BL/6 female hybrid mice. An identical number of control mice (of the same ages)from all three strains received similar transplants of pineal-sized, matched fragments of brain cortex tissue.

Results Of Transplant Studies

Every untreated control animal in all three groups was dead by 26 months of age, while at least one mouse in all three transplant groups was still alive at 31 months of age, and one hybrid mouse who received a pineal transplant survived until 33 months of age.

The three groups of aged mice receiving young pineal gland transplants lived 4-6 months longer than the control animals, which represents a 17% increase in survival for the 16-month-old C57BL/b mice, a 21% increase in survival for the 19-month-old hybrid mice, and a 27% increase in survival for the 22-month-old BALB/6 mice!

In another experiment, 20-month-old C57BL/6 male mice receiving pineal transplants from 3-month-old donors lived 12% longer than controls.

Rejuvenation After Pineal Transplants

When autopsies were performed on the aged mice who had received young pineal glands, the scientists found striking rejuvenation effects in the organs of the transplant recipients.

The first evidence of rejuvenation in the transplant recipients was the pineal gland itself, which had normal, viable clusters of pinealocytes (pineal gland cells) assembled within intact, youthful-looking structures.

Further evidence was the observations that both the thymus and thyroid glands had been rejuvenated in the experimental animals to a striking degree. After noting these effects, Pierpaoli and Regelson commented that:

"In the pineal-grafted animals, survival data are reINFOrced by the apparent juvenile morphologic state of the thymus and thyroid and the immune status of recipients despite their age. The maintenance of reinforced function is not surprising as melatonin and the pineal are known to enhance the immune response. This may well delay the appearance of tumors and autoimmune disease as factors in age-related pathology....

"Thymic and thyroid morphologic restoration occurs at a time when the normal involution of age is demonstrable. Our exogenous use of circadian melatonin and pineal engraftment of young pineals to the site of the thymus in aged mice suggests that there may be a firm relationship between the pineal, its products, and the thymus, providing a homeostatic control mechanism of significance for aging and survival. "

Questions About Lifespan Experiments