Young mice who exchange pineal glands with old mice alsoswap their respective life expectancies, a study has revealed.
The results of this cross-transplantation experiment will bepublished later this month by the New York Academy ofSciences in the volume of proceedings of a conference titled"The Pineal Gland and Other Pacemakers in the Progression ofAging and Cancer."
Italian physiologist Walter Pierpaoli organized this conference,the Third NATO Advanced Research Workshop on Aging andCancer, which was held last June on the Mediterranean islandof Stromboli. He also co-authored the cross-transplantationreport with Vladimir Lesnikov, a Russian physician andsurgeon.
Pierpaoli told BioWorld that their experiment demonstratedthat "pineal cross-plantation provides clear-cut evidence forthe central role of the pineal gland in the initiation andprogression of senes-cence."
In microsurgical procedures lasting up to two hours per animal,they removed the pineal glands from ten 4-month-old, inbred,immuno-compat-ible female mice and transplanted them intothe skulls of elderly rodents (18 months old) in place of theirown aging glands. Another ten young mice received thesesenescing pineals instead of their own youthful glands.
A separate cohort of 30 mice was given a sham operation. Theysurvived an average of 24 months, the average for laboratorymice and roughly eqivalent to the classical human life span of70 years.
Meanwhile, the youthful pineals engrafted into the 18-month-oldsters turned these elderly animals into murine Methuselahs;they survived on av-erage 34 months PP 40 percent longer thannormal. By a similar token, the "old" pineals implanted in theskulls of young mice cut short their existence to a scant 17months PP 40 percent less than the norm.
In reporting these criss-cross transplants at the Stromboliworkshop, Pierpaoli explained that the results proved that "thelife-prolonging or age-delaying effects observed were due tothe intrinsic properties of the pineal, not to non-specific chronicfactors such as food or water intake." The mice, he said, "werethemselves controls, donors and at the same time recipients ofan 'old' or 'young' pineal gland."
Pierpaoli is founder and director of the non-profit Foundationfor the Aged at Ancona, which is affiliated with the Italiangovernment's Center on Aging and the University of Ancona.His co-author, Vladimir Lesnikov, is from the Institute ofExperimental Medicine in St. Petersburg.
In humans, the pea-size pineal gland lies deep inside the skull,between the brain's two hemispheres. It is often called "thebody's third eye" because it is sensitive to light, especiallydaylight, as distinct from night darkness. The pineal is a high-yield factory for the production of neurohormones, melatoninin particular. Its output varies with the light-dark cycles ofcircadian rhythm. Pierpaoli said the pineal mediates seasonalaffective disorder (SAD) PP low-sunlight, high-latitude winterdepression.
The pineal's principal product and main presumptive mediatorof the aging process is melatonin, which is a deriva-tive ofserotonin.
In an experiment to test melatonin's effect on aging, Pierpaolifed the hormone to aging mice in their drinking water, but onlyduring the night. It prolonged survival of the elderly animalsfrom 23.8 months to 28.1 months, while "preserving aspects oftheir youthful state." He and his co-author, gerontologistWilliam Regelson of Virginia Commonwealth Universityreported these results in last month's Proceedings of theNational Academy of Sciences (PNAS).
In a separate gland-grafting procedure reported in the samePNAS paper, they transplanted pineals from three- to four-month-old postpubertal donors into the thymuses of 20-month-old recipient mice and induced a 12 percent increase insurvival.
Longevity: The Pineal Connection
These studies of melatonin's lifetime effect on the immunesystem suggest that it presumably postpones the onset ofcancer and autoimmune diseases until after childhood, youthand the prime of life. The PNAS authors onclude: "The dataindicate that pineal influences have a place in the physiologicregulation of aging."
Pierpaoli is planning to repeat and extend the cross-transplantation and other experiments he has conducted. Healso intends to attempt clinical trials to intervene in the humanaging process. "I believe we can even reverse I partially Iaging, and cure some aging-related diseases," he said.
Regelson noted that at least three drug companies areinterested in melatonin:
-- Interneuron Pharmaceuticals Inc. of Lexington, Mass.,expects to begin clinical trials with its melatonin analog IP100-9 for treatment of insomnia, before the end of 1994. Otherpotential indications include jet lag (transmeridiandysfunction), premenstrual syndrome (PMS), and, in light ofthe compound's circadian rhythm dependence, enabling shiftworkers to stay alert.
-- The French company Servier has developed melatoninanalogs to control circadian rhythms.
-- Glaxo Inc. is developing a series of melatonin analogs.
Regelson and Pierpaoli have a patent on melatonin to treatseborrhea, a minor but widespread skin disorder. They areabout to begin a clinical trial in Switzerland, where Regelsonsaid there is a big seborrhea market.
But Regelson predicts that "melatonin is not going to go veryfar, be-cause it's in the public domain. Every mother's sister'scousin has got a patent on it," he said, "including myself." Headded: "It's a problem because people without a composition-of-matter patent on this pineal hormone are not ready tolaunch this patent, because they can be jumped."
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.