Biologists Have Identified Pathways That Can Extend Lifespan up to 500 Years
Wed, April 21, 2021

Biologists Have Identified Pathways That Can Extend Lifespan up to 500 Years

A team of scientists identified cellular pathways that can extend the lifespan of a nematode worm—known as Caenorhabditis elegans or C. elegans—fivefold. The discovery of the cellular mechanisms behind this prolonged lifespan may help develop more effective anti-aging therapies to extend human life / Photo by: anyaberkut via 123RF

 

A team of scientists identified cellular pathways that can extend the lifespan of a nematode worm—known as Caenorhabditis elegans or C. elegans—fivefold. The discovery of the cellular mechanisms behind this prolonged lifespan may help develop more effective anti-aging therapies to extend human life.

The scientists used C. elegans for the study since most of its genes are similar to that of humans. These worms also have a short lifespan of only three to four weeks, providing a shorter waiting time to analyze the effects of various interventions in prolonging a healthy lifespan.

Scientists at the MDI Biological Laboratory collaborated with researchers from the Buck Institute for Research on Aging in California and Nanjing University in China to conduct the study, with results published in the peer-reviewed scientific journal Cell Reports.

Extending Lifespan

The average human lifespan is about 80 years, but the new study may provide the mechanism to prolong human life for up to 500 years.

Drawing on the discovery of two major pathways—the insulin signaling (IIS) and TOR pathways—facilitating the aging of the C. elegans, the researchers looked into the effects of genetic and environmental factors that can help extend the average lifespan. They wanted to identify the mechanisms that help the cellular pathways govern aging.

"By helping to characterize these interactions, our scientists are paving the way for much-needed therapies to increase healthy lifespan for a rapidly aging population," Hermann Haller, president of the MDI Biological Laboratory, said in a press release.

The IIS and TOR pathways are "conserved" pathways, meaning they are also present in humans thanks to evolution and have been the subject of intensive research.

Using double mutant to genetically alter these pathways, the researchers expected the double mutant to live 130% longer since alteration of the IIS pathways would yield to 100% lifespan increase and TOR pathway a 30% increase.

Surprisingly, the lifespan of the C. elegans amplified by 500%—a "really wild" synergistic extension, according to lead author Jarod A. Rollins.

"The effect isn’t one plus one equals two, it’s one plus one equals five," Rollins said in a statement. "Our findings demonstrate that nothing in nature exists in a vacuum; in order to develop the most effective anti-aging treatments we have to look at longevity networks rather than individual pathways."

Development of Anti-aging Therapies

The study focused on how longevity is facilitated in the mitochondria. Studies over the last decade yield to evidence suggesting a causative link between mitochondrial dysregulation and aging.

The discovery of the cellular mechanisms behind the interaction between the IIS and TOR pathways could help scientists develop more effective anti-aging therapies.

For corresponding author Pankaj Kapahi of the Buck Institute, identifying the synergistic interaction could open the door to the use of combination therapies that affect a different pathway to extend human life in the same way these therapies are used to treat cancer and HIV.

"The synergistic interaction may also explain why scientists have been unable to identify a single gene responsible for the ability of some people to live to extraordinary old ages free of major age-related diseases until shortly before their deaths," the press release on the study states.

The discovery of the cellular mechanisms behind the interaction between the IIS and TOR pathways could help scientists develop more effective anti-aging therapies / Photo by: rido via 123RF


Stress Can Also Prolong the Lifespan

In another study involving C. elegans, researchers from the University of Michigan found that stress in early life could lead to a longer life. They said oxidative stress experienced at a young age can increase stress resistance later in life.

Oxidative stress is when cells produce more oxidants and free radicals than they can handle—a normal part of aging. However, it can also occur during stressful situations like exercising and calorie restriction.

"If lifespan was determined solely by genes and environment, we would expect that genetically identical worms grown on the same petri dish would all drop dead at about the same time, but this is not at all what happens," Ursula Jakob, lead researcher of the study, said in a press release.

"Some worms live only three days while others are still happily moving around after 20 days. The question then is, what is it, apart from genetics and environment, that is causing this big difference in lifespan?"

The researchers determined that prolonged lifespan is partly caused by the uneven production of reactive oxygen species (ROS) during development. All air-breathing organisms produce ROS, which is linked with aging since the oxidative damage they elicit are what most anti-aging creams are said to combat.

Instead of having a shorter lifespan, the investigators found that C. elegans that produce more ROS during development lived longer compared to worms that produced fewer oxidants. This finding remained the same when the researchers exposed the whole population of developing worms to external ROS—resulting in an increased lifespan for the entire population.

"The general idea that early life events have such profound, positive effects later in life is truly fascinating," Jakob said.

"Given the strong connection between stress, aging, and age-related diseases, it is possible that early events in life might also affect the predisposition for age-associated diseases, such as dementia and Alzheimer’s disease."

Oxidative stress is when cells produce more oxidants and free radicals than they can handle—a normal part of aging. However, it can also occur during stressful situations like exercising and calorie restriction / Photo by: dotshock via 123RF