─ Nutrients should be moderate in the body—excessive supplementation only becomes a burden.
Antioxidants Don't Fight Aging?
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2013/03/14 05:07
508 topics published
‧ Scientific American 2013/03/13
Does oxidative cell damage cause aging? Can vitamins help us retain youth? Long-held beliefs are now being questioned!
【Author/Melinda Wenner Moyer; Translation/Lin Ya-Ling】
Key Points
■ For decades, researchers believed that highly reactive free radical molecules damage cells and gradually impair the function of tissues and organs, leading to aging.
■ However, recent experiments have shown that increasing certain types of free radicals in mice and nematodes may extend lifespan. In some cases, free radicals appear to act as signals that activate cellular repair networks.
■ If these findings are validated, they would suggest that taking vitamins or other forms of antioxidants may do more harm than good for otherwise healthy individuals.
The oxidative damage theory of aging has been around for a long time. The latest aging research directly challenges this long-held belief, with new discoveries increasingly appearing not as anomalies but as established principles.
Photo provided by Scientific American magazine.
In 2006, David Gems’ life was turned upside down by a group of stubborn nematodes that refused to die. Gems, the assistant director of the Institute of Healthy Aging at University College London, had been conducting experiments on the biology of aging using Caenorhabditis elegans. In this study, he aimed to examine whether persistent oxidative cell damage is the primary mechanism of aging. According to the oxidative theory, excessive accumulation of oxidative reactions leads to increasing damage to lipids, proteins, DNA fragments, and other key cellular components, ultimately impairing the function of tissues, organs, and the entire body.
Gems genetically modified the nematodes to prevent them from producing specific enzymes—natural antioxidants that eliminate free radicals. As expected, removing these antioxidants caused a sharp rise in free radicals within the nematodes, triggering destructive oxidative reactions throughout their bodies.
Contrary to Gems’ expectations, however, the mutant nematodes did not die prematurely and lived just as long as normal ones. The researchers were baffled. Gems recalled his reaction at the time: “This can’t be right. There must be some mistake.” He asked another researcher in the lab to review the data and repeat the experiment. The results remained the same: the modified nematodes indeed could not produce the specific antioxidant enzymes, and their bodies accumulated high levels of free radicals as predicted. Despite the severe oxidative damage, they did not die early. Other scientists have made similarly puzzling discoveries in different experimental animals.
Arlan Richardson, director of the Barshop Institute for Longevity and Aging Studies at the University of Texas, genetically engineered 18 strains of mice to produce either more or less of specific antioxidant enzymes. If free radical generation and subsequent oxidative damage were the cause of aging, mice with more antioxidant enzymes should live longer than those without. Richardson said, “But when I looked at their lifespan curves, there was no significant difference at all.” Between 2001 and 2009, he published a series of papers reporting these increasingly perplexing results.
Meanwhile, physiologist Rochelle Buffenstein, working near Richardson, spent the past 11 years trying to understand why the naked mole rat—the longest-living rodent—can survive for 25–30 years (about eight times longer than mice of similar size).Buffenstein's experiments showed that naked mole rats have fewer innate antioxidants in their early life compared to mice, and their tissues accumulate more oxidative damage. Paradoxically, however, they live remarkably long and healthy lives.
The oxidative damage theory of aging has been around for a long time, and for its proponents, these new findings are nothing short of heresy. Yet, based on the results, they seem less like exceptions and more like the rule. Over the past decade, many experiments designed to prove that free radicals and other reactive molecules drive aging have instead directly challenged the theory. These high-energy molecules, under certain conditions and concentrations, may not be harmful but instead activate the body's built-in defense mechanisms, helping us stay healthy. These ideas not only strongly impact future anti-aging interventions but also raise doubts about the effectiveness of high-dose antioxidant vitamin supplements. If the oxidative damage theory is wrong, then aging is more complex than researchers thought, and ultimately, we will need to revise our molecular-level understanding of healthy aging.
James noted, "The field of aging research has long followed established concepts. Shifting to the latest perspectives on aging is, in a way, like taking away the air we breathe. We should examine other theories and reconsider whether we need a completely different approach to understanding biology."
**[Evidence from Humans]**
**The Downsides of Vitamins**
Epidemiological studies show that people who consume large amounts of fruits and vegetables (rich in vitamins and other antioxidants) tend to live longer and have lower cancer rates than those who don’t. Thus, taking antioxidant supplements might seem beneficial. However, some rigorously designed studies do not support this hypothesis. Evidence suggests that people taking certain supplements may actually be more likely to develop life-threatening diseases such as lung cancer and heart disease.
**Early Research on Antioxidant Risks**
A 1996 study involving 18,000 men and women found that participants taking beta-carotene and retinol had a 28% higher incidence of lung cancer and a 17% higher mortality rate compared to those who didn’t take the supplements. These risks became more pronounced 18 months into the trial, particularly among heavy smokers, especially those exposed to the carcinogen asbestos.
**Final Conclusion: Certain Vitamins May Shorten Lifespan**
In 2007, researchers reviewed 68 rigorous vitamin studies and concluded that, based on data from the 47 most objective trials, vitamin supplements increased the risk of premature death by 5%. Further analysis linked this risk to beta-carotene, vitamin A, and vitamin E.
**[Full content available in *Scientific American*, March 2013, Issue 133]**
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