A Still Curious Case

Entertainment & Media / by Anthony Kaufman /

The Curious Case of Benjamin Button grapples with age-old fears of death and aging, physiological processes that modern science is only beginning to understand.

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Most researchers in the field of aging have far more modest aims — to provide humans with incrementally longer and healthier lives. “I wouldn’t be surprised if there’s a 5 to 10 percent increase in life span in the next 20 years,” says Dr. William Orr, chair of biological sciences at Southern Methodist University. “But the key benefit of all this research is that we’re going to feel better during that time.”

Orr studies oxidative stress — the “free radical” theory that the oxygen we breathe damages and disrupts our cells. By combating these oxidized molecules with antioxidants, some research suggests, negative affects on cellular physiology are reduced. In a study published in the Journal of Biological Chemistry in 2005, for example, Dr. Orr and his team increased the lives of fruit flies by 50 percent, by boosting an enzyme that regulates the synthesis of the antioxidant glutothione. But Orr acknowledges that translating such an approach for humans “is not terribly easy,” in part because some antioxidants turn to prooxidants at certain concentrations.

Orr also points to promising research that has linked the reduction of the level of insulin signaling, which tells the body’s cells to use sugar from the blood, to an increase in life span in mice. He also describes the “red wine effect” — research showing that resveratrol, a substance on the skin of grapes, activates a genetically controlled enzyme linked to longevity — as “a serious development.”

The anti-aging field’s favorite research subject continues to be caloric restriction (or “CR”), which has found a low-calorie diet to extend the lives of worms, fruit flies, mice, and rats. Pioneering U.C. San Francisco biochemist Cynthia Kenyon has also stated that a calorie-restricted diet in humans creates a situation where the body reacts by mounting a self-protective response, boosting antioxidants and the immune system.

In 2007 a study conducted on humans at the Pennington Biomedical Research Center found that a 25 percent reduction in calories for six months improved mitochondrial function and reduced DNA damage in the participant’s muscles. The study also saw an increase in sirtuins — those longevity-related genes — in participants’ skeletal muscles.

However, many scientists find flaws in the promise of caloric restriction for humans. Researchers at the Washington University School of Medicine in St. Louis published a study in the September issue of the journal Aging Cell in which humans on long-term calorie-restricted diets had no change in a growth factor called IGF-1 (insulin-like growth factor-1), a key aspect of life span extension in animal studies. Dr. Rajindar Singh Sohal, a USC professor of pharmacology and pharmaceutical sciences who researches caloric restriction, also remains unconvinced. “Only those that get fat are going to gain from CR,” Sohal says, “because getting fat is injurious. We have incontrovertible evidence that fat itself produces these substances that cause oxidative stress. But it does not work in all species.”

As groundbreaking as they are, none of these scientific advances could have fought off the ultimate end for Benjamin Button and his lifelong love, Daisy (played by Cate Blanchett), a famous ballet dancer who, in her youth, has ivory skin and a lithe, slim line. Through the course of the film, Daisy’s body sags, she develops bags under her eyes, gray hair, and finally, liver spots and failing organs. As she cries out during middle age, “I just don’t like getting old!”

The sentiment is all too familiar these days. As the average human life span has almost doubled over the past century, the clamoring to turn back or at least slow down the clock has intensified. Based on the latest science, there is hope yet for another dozen, healthier years in our future, but a lithe, active body or youthful face at 70 or 100? As Dr. Sohal says, “We are still at a stage where we have to understand the causes of aging, so it’s a bit premature to find the remedy.”

For now, we’ll have to heed the words of Benjamin Button: “When it comes to the end, you just have to let go.”

Originally published December 24, 2008

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