Autophagy Unraveled
Researchers have discovered that autophagy genes in worms, which are crucial to the cellular survival process in all species, drive the aging process later in life after promoting health and fitness in young specimens. The research revealed that neuronal and whole body health improved, and longevity with it, when autophagy was shut down in old worms.
This provides proof that the aging process evolved, and offers hope for treating neurodegenerative disorders related to autophagy, like Alzheimer's, Huntington's disease, and Parkinson's.
Although getting old has traditionally been considered an inevitability, in recent years more people have been questioning whether it should be. Since aging would seem to prevent species from multiplying as effectively, aging itself might appear to be an evolutionary contradiction.
However, starting in 1953, aging began to be understood as a predictable result of evolution when the antagonistic pleiotropy (AP) hypothesis was proposed. This theory states that a gene mutation that results in more offspring will be passed on as an advantage, even if it shortens life; the mutation means the carrier will have more descendants to pass on its genes, making up for its shorter lifespan.
Over time, the aging process becomes hard-wired into our DNA, as pro-aging mutations are actively selected for in the evolutionary process.
This theory has finally been backed up by evidence. The study in this case was able to study AP genes in older animals on a large scale. This allowed them to identify 30 genes that promoted aging — a surprisingly large number, and some of the first discovered to cause the process in old test subjects. Moreover, this research tested only 0.05 percent of all of the genes in the subject worms, indicating that there may be many other such genes yet to be identified.
Second Shift
Perhaps even more interesting than the connection between aging and evolution are the other processes the aging genes control. Autophagy — which, earlier in life, eliminates unneeded or dysfunctional cell components — deteriorates over time, and the researchers found that bypassing the process altogether allowed the worms to live longer than allowing it to run while crippled. In other words, the conventional wisdom that autophagy is beneficial, even when barely working, appears to be wrong.
The researchers tracked pro-longevity signals to the neurons and inactivated the autophagy process in the old worms. By doing so, they improved the overall health of the worms, as well as prolonged their lives.
“Imagine reaching the halfway point in your life and getting a drug that leaves you as fit and mobile as someone half your age, who you then live longer than. That's what it's like for the worms,” co-lead author Thomas Wilhelm, of the Institute of Molecular Biology in Mainz, Germany, told Medical Xpress. “We turn autophagy off only in one tissue and the whole animal gets a boost. The neurons are much healthier in the treated worms, and we think this is what keeps the muscles and the rest of the body in good shape. The net result is a 50% extension of life.”
Although the researchers do not yet know the precise mechanism that allows the neurons to remain healthier for longer, these findings could represent a way to preserve neuronal integrity in diseases associated with autophagy, such as Alzheimer's, Huntington's, and Parkinson's disease. This kind of treatment will be far into the future, if the findings can be validated in humans, but they offer the possibility of preventing age-related disease and improving health.
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