By 1972, Dr. Harman had invested fifteen years of his life into testing antioxidants as potential anti-aging therapies. 88 89 90 He'd tried a host of them, from natural ones like cysteine,90 hydroxylamine, 90 and vitamin E 89 to potent synthetic antioxidants like ethoxyquin89 and "radioprotectors" such as 2-mercaptoethylamine. 89, 90
In some ways, it must have been the most frustrating fifteen years of his life.
Dr. Harman had repeated the same basic experiment over and over again with different antioxidants, but the result was always the same. Time and time again, the supplements made the animals healthier, and gave them a longer life expectancy. But there was a catch: none of these antioxidants had any significant impact on the maximum lifespan of the species - the length of years which members of the species never exceed if they are allowed to live out their "natural" lives.
The failure was crucial. An organism may get a specific disease because of a toxic environment, or a poor lifestyle, but the rate of aging is a function of fundamental aspects of the design of the organism itself. That fact is reflected in the very existence of a maximum lifespan for the species. So if you're really impacting the essence of aging, you should see clear changes in this crucial parameter. Animals on a true anti-aging program should experience increases in maximum lifespan.
Generations of scientists after Harman have reported the same results. This crucial difference is widely believed to explain why antioxidant supplements have failed, again and again, to slow down intrinsic aging. Scientists have tried to slow intrinsic aging and break maximum lifespan using a host of antioxidants. They've tried combinations of beta-carotene, alpha-tocopherol, vitamin C, selenium, zinc, and the flavonoid rutin; 91 or of alpha-tocopherol, glutathione, melatonin, and polyphenol-rich strawberry extract. 92 They've tried CoQ10, 93 94 and they've tried a host of synthetic antioxidants. 95 Consistently, the result is the same. The animals live better - but not remarkably longer. Likewise, later researchers have found that there's also no consistent relationship between maximum lifespan and the levels of the various antioxidants that occur naturally in the bodies of animals. 96
The question was, why? Was the theory simply wrong - did the raging cellular damage caused by free radicals really have nothing to do with aging? That seemed almost impossible. But if so, then why do conventional antioxidants not protect these animals from aging?
In 1972, the lightning of insight struck Dr. Harman a second time.
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