Sharif Ezzat
In another first for Buck science, the Melov lab showed that aging in humans can be reversed through exercise, specifically strength-training. The lab did genetic studies on muscle samples taken from both younger and older adults before and after a 6-month resistance training regimen. After training, the “genetic fingerprint” in the muscles of older adults had reverted to more closely resemble the genes active in the muscles of younger adults.
Scientists at the Buck found the first compound shown to extend lifespan! Buck professors Simon Melov and Gordon Lithgow were the first to show that a drug-like compound could extend lifespan in an animal. The compound was an antioxidant. The animal was the roundworm C. elegans.
Tom Johnson’s discovery in 1988 that a single genetic mutation, dubbed age-1, could increase the lifespan of the roundworm C. elegans by up to 65% catalyzed the modern era of research on aging. Further interest in the field was driven when Cynthia Kenyon published in 1993 that a mutation in the daf-2 gene doubled the worm lifespan. Research on age-1, daf-2, and other genes in their molecular network have led to profound discoveries about the role of nutrient signaling in aging, which forms one of the major pillars of the field.
Telomeres are protective sequences of DNA that sit at the tips of our chromosomes and have been compared to the caps at the end of shoestrings. They get shorter with age. Cells with critically short telomeres can no longer divide, making short telomeres a hallmark of aging. Elizabeth Blackburn made the discovery of telomeres in 1978, and in 1985 she discovered the enzyme telomerase, which can lengthen telomeres. She won the Nobel Prize for this work, which began in single-celled organisms called Tetrahymena thermophila, commonly known as pond scum.
Leonard Hayflick discovered that human cells grown in the laboratory can only divide about 60 times, a phenomenon now called the Hayflick Limit. Cells eventually enter a state called cellular senescence, which occurs when cells stop dividing and growing, but do not die. Instead, they remain and continue to release chemicals.
The first study identifying a method to extend lifespan was published in 1939. This landmark study by McCay, Crowell, and Maynard found that caloric restriction (a diet that meets nutritional requirements but provides greatly reduced calories) in rats could increase their average lifespan. The biological mechanism of caloric restriction, and whether it works in humans, remains an important question in research on aging today.
