The role of dietary restraints in slowing aging and increasing longevity between organisms ranging from worms to primates is well known. Now a multi-institutional team from India has figured out one of the mechanisms by which the worms (C. Elegans) exposed to moderate stress at an early age in the form of dietary restrictions are able to cope with the chronic stress that comes with aging. The role of stress it does its job more effectively later in life, thus slowing down aging and increasing longevity. Moderate early-stage stress essentially primes the endoplasmic reticulum to cope with age-related stress later in life. It also slows the occurrence of age-related diseases such as Huntington and Alzheimer's.
Instead of restricting the diet, the researchers used a small molecule at an early age in small doses for 24 hours to produce the same kind of stress in C. C. ELEGANCE. They were able to slow down aging and increase longevity.
The endoplasmic reticulum is responsible for much of the requirements for cellular protein folding and the destruction of extremely misfolded proteins. Typically, the ability of the endoplasmic reticulum to fold proteins and destroy misfolded proteins is compromised with aging. "Priming helps delay the deterioration of the endoplasmic reticulum when folding proteins," says Dr. Latika Matay of NII and co-author of a paper published in Proceedings of the National Academy of Sciences (PNAS).
"Worms subjected to dietary restriction early in life show a 30-40% increase in longevity compared to C. elegans that were not diet restricted," says e ̵
The endoplasmic reticulum requires glucose for optimal protein folding. So when using the small molecule, glucose availability is limited and the organelle is stressed by the load of misfolded proteins. The stress control mechanism adjusts and tries to either fold the proteins properly or break them down.
Priming helps the endoplasmic reticulum to deal with stress as the worm progresses. "We've seen about a 20% increase in worm life when the small molecule is used alone," says Dr. Matay.
"Using the small molecule, we were able to simulate stress in mouse cell lines. We then challenged the cells to produce protein aggregates and could see the cells suppress and degrade the aggregates better than controls. As a result, the cells survived better, says Dr. Mukhopadhyay.
Delaying the onset of the disease
In addition to delaying aging and increasing life, priming the endoplasmic reticulum with low stress helps to delay some early-onset diseases such as Huntington and Alzheimer's.
With aging, the mechanism of protein folding is usually disrupted and so the protein tends to fold more tightly and the aggregates tend to form. Protein aggregates cause Huntington and Alzheimer's. "In C. elegans under stress, we can observe a slowdown in protein aggregation and a decrease in the number of aggregates. The delay in aggregation is more noticeable (50%) than that observed in controls, "says Dr. Matay.
" It is now important to test mouse models for Huntington and Alzheimer's, "says Dr. Muhopadhey p.