International research group finds 17 different genetic interventions that extend life.
Researchers in Moscow and Harvard have been able to identify a group of genes that, in response to a variety of interactions, exhibited activity associated with Longevity. This meant they could be categorised as biomarkers of lifespan extension.
Scientists from Skolkovo Institute of Science and Technology (Skoltech) in Moscow, Moscow State University and Harvard University decided to focus on identifying the important molecular processes linked with Longevity and life extension. They examined the step-by-step processes of genetic interventions in mice (often used in laboratories due to their biological similarity to humans).
Longevity.Technology: Rather than work on specific interventions, these researchers decided to breakdown the actual molecular processes involved, leading to a better understanding of how Longevity can be achieved on a molecular level. Development of an app also shows a savvy approach to life-extension applications in the real world as well as providing a tool to discover new interventions.
The TRL score for this Longevity.Technology domain is currently set at: ‘Principles are demonstrated through experimentation.’
The TRL score for the technology addressed in this article is: “Early proof of concept demonstrated in the laboratory.”
Research has discovered numerous interventions that can extend the lifespan of a whole variety of organisms from yeast to worms to mammals. These life-extending interventions include chemicals like rapamycin (a drug found originally in Easter Island bacteria), behaviours such as fasting (calorie restriction promotes autophagy, a process whereby the body cleans out and regenerates its cells) or genetic interventions like mutations (when growth hormones are disrupted, lifespan can be extended [1]).
Although some of the targets of these interventions have been discovered and mapped, scientists have not had any clear understanding of the systemic molecular pathways that detail these routes to extended lifespan. Not until now, that is.
Lead researcher Alexander Tyshkovskiy explained: “In our lab, we subjected mice of different sexes and ages to 8 longevity interventions and analyzed gene expression changes induced by these treatments. Although in general the effects produced by individual treatments turned out to be rather specific, a certain group of genes changed its expression in a similar way in response to different lifespan-extending intervention [2].”
Once the team had established these “longevity signatures,” and determined both general and specific transcriptomic details of lifespan extension, they looked for different interventions in order to identify new “lifespan-extending candidates [3]”. These included chronic hypoxia, KU-0063794, and ascorbyl-palmitate [4], an ester created from ascorbic acid and palmitic acid that creates a fat-soluble form of Vitamin C.
The team also developed GENtervention; this clever app demonstrates associations between gene expression changes and Longevity and puts the gene expression profile data online in a freely-accessible form [5].
The team is looking to expand the impact of this research; “Currently, we are validating these hits by testing their effect on the mouse lifespan. We hope that our biomarkers will significantly facilitate the search for new longevity interventions and help improve the healthspan and lifespan in rodents and, in the long term, in humans,” says Alexander Tyshkovskiy [6].
