Long ago, many scientists believed that aging occurs as the body deteriorates over time. It was thought that only lifestyle factors and a list of diseases contribute to determining our lifespan. However, a groundbreaking finding, published in 1993, changed the way scientists thought of aging.

“The idea that ageing was subject to control was completely unexpected.” Cynthia Kenyon

In the early 1990s, it was hard to grasp that a set of genes — or perhaps one — could control aging. But, Cynthia Kenyon, a molecular biologist and biogerontologist, believed that it was possible. She hypothesized that some gene(s) is responsible of us aging, thereby we could control aging by manipulating it.

In her lab, located at the University of California, she and her team started experimenting on microscopic roundworms called Caenorhabditis Elegans. These roundworms were a perfect target for research because they had a short lifespan and genes that were easily manipulated. To find out which genes affected lifespan, they randomly introduced genetic mutations and observed the response. They used a technique called temperature-sensitive mutations which allowed roundworms to develop normally under permissive temperature. The mutations were activated only after hatching when the scientists raised the temperature, therefore, allowing offspring to develop normally in their eggs1.

During the observation, in 1993, they discovered that some of the roundworms outlived the normal ones by a double amount of years. Disabling a single gene, DAF-2, allowed some worms to live twice as long as normal ones – called wild type.

According to Cynthia, “It was very profound because you look at these worms, and the normal worms are dying, and the worms in this other culture dish are young. And you think: ‘Oh my God, they should be dead.’ It was like finding something that shouldn’t be. It makes your hair stand up.” It appears that the DAF-2 mutants stay healthy for the entire period as well. As they age, the tissues of both wild-type and DAF- 2 mutants become progressively more mottled and disorganized; however, this physical decline occurs at a much slower rate in the mutant2. What is also promising is that these DAF-2 mutants are also resistant to old-age diseases, which really makes sense since these diseases often occur because of the effects of aging. This profound discovery, however, raises a lot of questions. What exactly DAF-2 is responsible of and would it be possible to apply the same method on humans?

In Cynthia’s TED Talk, she explains that the DAF-2 gene encodes a hormone receptor that “catches the hormone as it comes by [outside of the cell] and the other part is from the inside where it sends signals into the cell.” These signals are actually responsible for speeding up the aging process. The DAF-2 hormone receptor, found in these worms, is actually similar to two human hormone receptors: the receptors for insulin, a hormone that promotes the uptake of nutrients, and IGF-2, a hormone that promotes growth3. This suggests that the limiting of these two hormones can result in an extended lifespan. In fact, lifespans of mammals, and, to a limited extent, C. elegans, can be increased by food limitation1.

How exactly does the limiting of these hormones delay aging is a far more complex process. Further research imply that the deactivation of these receptors activates a gene regulator protein called FOXO. Briefly, this gene helps activate a whole other new set of genes which does a better job at repairing and protecting the tissues, as well as making them live longer.

Regarding the worms, we are glad that some of them got to live longer. But, what about us? Cynthia seems to be very optimistic for many reasons. She points out that damaging the genes encoding insulin or IGF-1 receptors can extend the lifespan of other animals too such as flies and mice. As we know, mice are mammals like us. She also refers to studies showing that humans inclined to age a 100 years old are more likely to have mutations in the DAF-2 gene. There are also certain forms of the FOXO gene that have found to be more frequently present in people who live to be 90 or 100, she says3.

“I’m really optimistic, and I think it won’t be too long, I hope, before this age-old dream begins to come true.” C. Kenyon

Cynthia’s ultimate goal is to actually move from her microscopic worms to humans. “We are trying to find drugs, small molecules, that people could take to make them disease-resistant, more youthful and healthy. Eventually we will find them.”

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Written by Zein Hanouneh