Successful Life Extension Study Is a Sign That Human Aging Could Be Stalled

What works for worms could work for us too.

Unsplash / Huyen Nguyen

On average, humans live to be about 72 years old. But a tiny worm, Caenorhabditis elegans, could help change that, even though it lives for just two to three weeks. Despite this difference in longevity, C. elegans — a transparent, one-millimeter long roundworm — might be what helps humans live longer, healthier lives. That’s because scientists recently discovered how to dramatically extend the worm’s lifespan with a technique they suspect could help us as well.

In a study published in the October issue of the journal Developmental Cell, scientists affiliated with the National University of Singapore report that giving these tiny worms a mixture of pharmaceutical drugs both increases their lifespan and delays their rate of aging. These drugs — which included rapamycin, rifampicin, Psora-4, allantoin, and metformin — were chosen because previous animal model studies found they interact with proteins and extend lifespan. Now, scientists discovered that pairing two of these drugs extended the lifespan of the worms, and combining three doubled their lifespan.

Jan Gruber, Ph.D., the study’s principal investigator, is an assistant biochemistry professor at Yale-NUS College, a collaboration between Yale University and the National University of Singapore. He believes that this research can one day alleviate the financial and societal burdens of aging.

“If we can find a way to extend healthy lifespan and delay aging in people, we can counteract the detrimental effects of an aging population, providing countries not only medical and economic benefits, but also a better quality of life for their people,” Gruber said on Monday.

A microscopic image of the Caenorhabditis elegans worms used in the study.

Dr. Jan Gruber 

The effect found in this study was larger than that found in similar studies in which drug interventions were used to extend the lifespans of animals. By targeting the overlapping segments of the genetic network that regulates aging, Gruber and his team were able to slow down the worm’s biological aging rate by around 20 percent. There was also a demonstrable change in the worm’s lipid metabolism, which they believe affected the gene-regulatory network that controls aging.

Drug combinations that work for C. elegans could likely work for humans as well because it’s hypothesized that we share evolutionarily conserved aging pathways. In a previous study, Gruber also found that a similar drug cocktail extended the lives of fruit flies (Drosophila melanogaster). Because the fruit fly and *C. elegans are evolutionarily distant from each other — their common ancestor lived about 1.2 billion years ago — but the cocktail induced complementary results, the team reasons that there are “synergies between pathways controlling lifespan” that have “been present in the phylogenetic tree for at least a billion years and likely trace back to a common ancestor more ancient than that.” This ancient ancestor is likely why such different animals — including humans, worms, and flies — would be affected similarly by a specific set of drugs.

Now that the scientists know something about the application of these drugs is causing the worms to live longer, their goal is to figure out exactly what molecular and biological mechanisms are causing this to happen. The ultimate goal is to develop something that can help humans age slower and experience fewer illnesses linked to aging, like cardiovascular disease, cancer, and Alzheimer’s disease.

There is growing interest in pharmacological interventions directly targeting the aging process. Pharmacological interventions against aging should be efficacious when started in adults and, ideally, repurpose existing drugs. We show that dramatic lifespan extension can be achieved by targeting multiple, evolutionarily conserved aging pathways and mechanisms using drug combinations. Using this approach in C. elegans, we were able to slow aging and significantly extend healthy lifespan. To identify the mechanism of these drug synergies, we applied transcriptomics and lipidomics analysis. We found that drug interactions involved the TGF-b pathway and recruited genes related with IGF signaling. daf-2, daf-7, and sbp-1 interact upstream of changes in lipid metabolism, resulting in increased monounsaturated fatty acid content and this is required for healthy lifespan extension. These data suggest that combinations of drugs targeting distinct subsets of the aging gene regulatory network can be leveraged to cause synergistic lifespan benefits.
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