For many years, researchers have been on a quest for therapies that can increase healthy lifespan in humans. Research into ways to promote longevity kicked into high gear following the finding in the 1990s that a single gene mutation in worm led to a dramatic increase in its lifespan.
Molecular biology researchers have been trying to unravel the genetic mechanisms having a link to the aging process. But they have found them harder to work out than they originally thought it might be.
MDI Biological Laboratory researchers Jarod Rollins, Ph.D., and Aric Rogers, Ph.D., have now described in a paper published in Life Science Alliance the mechanisms that regulate aging post-transcriptionally.
The discoveries, which are the results of five-year research by these scientists, could help in creating treatments that enhance a long life.
“Because it identifies new potential drug targets in the form of the post-transcriptional mechanisms governing longevity, this research will be hugely important in screening for new therapies to extend healthy human lifespan,” said MDI Biological Laboratory President Hermann Haller, M.D.
Rollins and Rogers carried out the research using C. elegans. This worm model shares genetic similarity with humans and, as such, is commonly used in aging research.
Developing DR mimetics
Scientists have taken an interest in dietary restriction (DR) as a means of prolonging a healthy lifespan. There is research showing this practice, which entails reducing calorie intake without suffering malnutrition, helpful for preventing age-related disorders and boosting longevity.
However, dietary or caloric restriction is not easy to practice. There are also some side effects that could come with it, including loss of energy and increased cold sensitivity.
Researchers have, therefore, been trying to develop DR mimetics – drugs mimicking DR’s effects. The current work could potentially lead to the development of more potent DR mimetics.
Rollins and Rogers made use of bioinformatics methods in their study. They compared the genes of worms given normal diets against those of worms on dietary restriction.
The researchers were able to spot the mechanisms that could be aimed at with drugs for longevity.
“With this research, we are drilling down to additional layers of regulation, which brings us one step closer to extending healthy human lifespan without the need to dramatically restrict calories or to take drugs that, because they are less selectively targeted, are more likely to cause adverse reactions,” Rollins said.
DR activates adaptive mechanisms in cells. When there are insufficient nutrients, cells use what is available for survival rather than growth and reproduction. This scarcity makes the cells more efficient, and this is a good thing for health.
The MDI Biological Laboratory research confirms theories on the adaptive response induced by DR.
The researchers were able to identify the mechanisms that regulate gene expression at post-transcriptional levels.
By post-transcriptional regulation, reference is to the regulation that takes place when a gene has been “transcribed” or “read” from the DNA in a cell’s nucleus.
The discovery of these mechanisms opens the way for the screening of more effective drugs that could promote a longer healthy lifespan.
“We found that hundreds of genes are being regulated almost solely at the post-transcriptional level,” said Rollins. “These are genes that weren’t previously known to have a role in longevity. This level of regulation can be missed if scientists are looking at the transcriptional level alone.”
The lifespan-extending potential of DR has been shown in a variety of species, ranging from single-cell organisms to primates. This research provides more knowledge of how it works.
Articles you May like: