The role of nutritional restrictions in delaying aging and increasing life expectancy in organisms, ranging from worms to primates, is well known. Now, a multi-institutional team from India has uncovered one of the mechanisms by which worms (C. elegans) who are exposed to an early, moderate stress in the form of dietary restrictions can deal with chronic stress comes along with the Aging.
The role of stress
Arnab Mukhopadhyay from the National Institute of Immunology (NII) in Delhi also showed that certain organelles in the cells (endoplasmic reticulum) are stressed early by dietary restrictions can do his job more efficiently later in life, thereby delaying aging and increasing lifespan. Moderate stress at a young age prepares the endoplasmic reticulum mainly to deal with age-related stress later in life. It also delays the onset of age-related diseases such as Huntington's and Alzheimer's.
Instead of diet restrictions, the researchers used a small molecule in small doses for 24 hours to produce the same type of stress in C. elegans. They could delay aging and increase lifespan.
The endoplasmic reticulum is responsible for much of the demands on cellular protein folding and the destruction of terminal misfolded proteins. Normally, the ability of the endoplasmic reticulum to fold proteins and destroy misfolded proteins is compromised by aging. "Priming helps delay the deterioration of the endoplasmic reticulum in protein folding," Dr. Latika Matai of the NII and co-lead author of a paper published in the Proceedings of the National Academy of Sciences (PNAS).
"The worms, which were subject to diet restriction at a young age, showed a 30-40% longer lifespan compared to C. elegans who had no dietary restrictions," says Dr. Mukhopadhyay. "We can bypass the diet restriction to induce stress by using a small molecule." It has been found that a small dose of the molecule, which is a form of glucose that can not be used by the cells and is administered 24 hours at the beginning of life, stimulates the endoplasmic reticulum and enhances protein folding capacity and degradation of aggregated proteins In adults.
Endoplasmic reticulum requires glucose to optimally fold proteins. When the small molecule is used, the availability of glucose is limited and the organelle is burdened by the charge of misfolded proteins. The defense mechanism against stress is upregulated and attempts to properly fold or break down the proteins.
The primer helps the endoplasmic reticulum to cope with stress as the worm ages. "We observed an increase in worm life of about 20% when only the small molecule was used," says Dr. Matai.
"By using the small molecule, we were able to mimic stress in mouse cell lines. We then made the cells produce protein aggregates, and we could see that the cells better suppress and degrade the aggregates than the controls. As a result, the cells survived better, "says Dr. Mukhopadhyay.
Delaying the onset of disease
In addition to delaying aging and extending lifespan, priming the endoplasmic reticulum with low stress helps treat certain age-related diseases such as Huntington's and Alzheimer's.
With increasing age, the protein folding mechanism is generally compromised, causing the protein to misfold and form aggregates. Protein aggregates cause HD and Alzheimer's. "In C. elegans stress, we observed a delay in protein aggregation and a decrease in aggregate numbers. The delay in aggregation was 50% more pronounced than in the controls. "
" It is now important to test them on mouse models of HD and Alzheimer's, "says Dr. Mukhopadhyay.