Decoding Aging for Making 80 the New 40

By Crystal Tai

The fountain of youth legend goes back to the fifth century BC, appearing in writings by Herodotus, but not until recently did scientists make a real breakthrough in reversing aging.

The Stuart Kim Lab of Stanford University School of Medicine has successfully rejuvenated nematodes. Generally, nematodes live about 20 days. An 18-day-old nematode can hardly move, under normal circumstances. However, the Stuart Kim Lab has managed to double a nematode’s life span and make the 40-day-old stay as active as a 10-day-old!

“The key to the nematode’s rejuvenation is ELT-3, a transcription factor that regulates a large number of downstream genes,” said Dr. Stuart Kim, professor of the departments of Developmental Biology and Genetics at Stanford University.

Dr. Kim explained that ELT-3 declines in the nematode with age, and that subsequently leads to the degeneration of all the cells it regulates. However, once ELT-3 is artificially enhanced in the lab, all the cells are recharged, and the nematode regains its youth.

Can the nematode experience be applied to human beings? According to Dr. Kim, comparable mechanisms have been found in the human brain, heart, muscles, and kidneys.

Wear & Tear vs. Developmental Drift

The discoveries of the so-called “master regulators” in human beings challenge the traditional view of aging which attributes its cause to only wear and tear. The new theory of aging, developmental drift, states that aging happens when master regulators become less functional and organismal development goes awry.

To make the two theories easier to understand, Dr. Kim compares the human body to an automobile.

“An old person doesn’t move very fast, just like an old car,” said Dr. Kim. “The old theory says the car gets old because its parts are worn out, but we think there’s more to it. We’ve found master regulators, each of which can turn on or turn off hundreds of genes.”

“In a car, the master regulator is the gas pedal,” he explained. “In animals and people, the master regulators are transcription factors and growth factors. It’s exciting to know these master regulators. Think about it. With the wear and tear model, we cannot fix all the parts that have been worn out. But if aging is just the gas pedal not being pushed down hard enough, you can push it harder. It’s much easier to fix.”

Fighting Aging = Best Way of Disease Prevention

Dr. Kim said the fight he puts up against aging is meant to prevent diseases, because aging makes people prone to get sick.

According to Dr. Kim, mortality rate doubles every 8.6 years from age 20 to 80. He said the trend appears to continue after age 80, though the statistics do not include the 80-plus age group due to the lack of data. In other words, the older we get, the more likely we will die of a disease. Young patients have a much better chance of survival than elderly ones.

Dr. Kim calls age 10 the year during which the human body is the strongest.

“It’s hard to kill a 10-year-old,” he said. “If we could all keep a 10-year-old’s physical conditions, we would have a life span of 5,000 years!”

While that appears inconceivable, there are some super centenarians in the real world.

Super Youthful Genes in Super Centenarians

Compared with centenarians, who are 100 years old or older, a super centenarian by definition is someone who has lived at least 110 years. According to Dr. Kim, there are currently 85 super centenarians worldwide, and his lab is studying 17 of them. These 17 American citizens or residents are originally from all over the world.

Perhaps surprisingly, none of these 17 super centenarians can be called a health nut. They don’t diet. Some of them haven’t done much exercise throughout their lives. Some of them even have been long-term smokers. However, they live long and well. Quite a number of them still walk and stay mentally alert. They also look great. Dr. Kim says they look like healthy 80-year-olds to him.

Since their extraordinary longevity and remarkable health cannot be attributed to lifestyle, the only explanation is their genes. Another fact supporting the new theory is the 40-year average life span of chimpanzees. According to Dr. Kim, human beings share 98 percent of the genes with chimpanzees, and it’s the two-percent difference that makes most of us live about twice as long.

The Stuart Kim Lab is currently studying samples of the super centenarians’ genes in the hope of finding something applicable to the well being of the entire mankind.

Master Regulators in the Human Body

So far, two master regulators in the human body have been found to have the most significant impact on aging. They are GDF11, which stands for “growth differentiation factor 11,” and STAT3, standing for “signal transducer and activator of transcription 3,” which is a transcription factor.

With age, GDF11 will become too low and STAT3 too high. According to Dr. Kim, insufficient GDF will weaken the brain, the heart and the muscles; excessive STAT3 tends to induce inflammation, resulting in poor kidney function.

After identifying these root causes of aging, researchers are working on fixing them.

Possibilities of Rejuvenation in the Foreseeable Future

Dr. Kim said it should be feasible to purify GDF11 and give it to elderly patients through injection in the foreseeable future.

He said it would be harder to take away excessive STAT 3 from the kidneys, but researchers should be capable of inventing medications to suppress it.

“We’ll be able to reverse some effects of aging in our lifetime,” he added.

--Crystal Tai is a South Bay-based journalist.