Span Extension in Animals
In my introduction, I discussed the experiment by Maestroni and colleagues, published in 1988, that found an average 20% increase in longevity in middle-aged, male mice when they were given melatonin in their nightly drinking water. The researchers state, "To our surprise, chronic, nightly administration of melatonin resulted in a progressive, striking improvement of the general state of the mice and, most important, in a remarkable prolongation of their life. In fact, starting at 5 months from the initiation of melatonin administration, the body weight of the untreated mice still surviving started to decrease rapidly, and also astonishing differences in the fur and in the general conditions of the 2 groups (vigor, activity, posture) became increasingly evident. Melatonin treatment preserved completely optimal pelage (fur) conditions."

A similar experiment on middle-aged, male mice, done in 1991 by Pierpaoli and colleagues, also found a 20% increase in life span.

What would melatonin do in the young? To find out, Pierpaoli and colleagues gave melatonin every night to young, female mice (strain C3H/He) starting at age 12 months until death. (There are various strains of laboratory mice and the effect of a particular substance may be different on each strain. That's why it's important to mention which one.) The average life span in this strain of mice is about 24 months. The age of 12 months (pre-menopause) would correspond roughly to age 35 in humans. To the surprise of everyone, melatonin shortened life span by 6%. A high rate of ovarian cancer occurred in these young mice. Apparently there are cells in the ovaries in this strain that overgrow when stimulated by melatonin, causing tumors. Another strain of young, female mice (NZB) was also given melatonin nightly starting at age 12 months, and they lived longer than the untreated group. A third group of NZB strain female mice was given melatonin at 5 months of age (Pierpaoli, 1994). They also lived longer than those not on melatonin. Obviously, different mouse strains respond to melatonin differently.

It is possible that if the mice who developed ovarian cancer had been given a lower dose of melatonin, they may have fared better. Based purely on a weight ratio, the amount of melatonin given the mice was many times the dose a human would normally use at night for sleep.

How did melatonin affect female mice who already had reached menopause? In one study, when 18 month old post-menopausal mice (strain C57BL/6) were given melatonin nightly, ovarian cancer was not detected. They lived 20% longer than those who were not given melatonin.

How can we interpret these animal studies in order to make practical recommendations for us humans? First, we have to realize that rodents and humans may respond differently to the same medicine. We have seen that even different strains of mice respond differently. We know by experience, however, in countless other studies and with various other medicines that there is often a similarity between the effects of a substance on rodents and that on humans. We should also consider the possibility that while one person may benefit from a medicine, another may be harmed. Just as there are differences in response between different strains of mice, there may be differences in response between different human beings.