For thousands of years, we've been searching for a way to extend our lives — without much luck. The average human lifespan in developed countries has more than doubled from 37 to 79 in the past 200 years, but most of that gain is attributable to reduced infant mortality. When it comes to adding years of adult life, we've barely moved the needle.
But things may be about to change — in part because of one very chilly fish.
Deep in the icy waters of the Arctic, the Greenland shark (Somniosus microcephalus) has already mastered the art of living for centuries. Scientists believe this odd species may hold secrets to prolonging our own lives.
Last year, scientists reported in the journal Science that S. microcephalus can live for about 400 years, and possibly much longer. The extreme life span of this species — now believed to be the world's longest-lived vertebrate — was discovered via radiocarbon dating of proteins in the sharks' eyes.
Since that research was published, scientists in Denmark, England, and elsewhere have been trying to figure out why these fish live so long — and what to make of the fact that they seem to avoid cancer, heart disease, and other ailments that go along with aging in humans.gi
One possible explanation for the sharks' longevity is that they spend their lives 2,000 meters down, where the water temperature is around 29 degrees Fahrenheit. Extreme cold is associated with slow metabolism and maturation — Greenland sharks don't reach adulthood until age 150 — as well as long life spans.
Of course, humans aren't about to start living underwater. But scientists think we might be able to incorporate into our own bodies some of the shark's life-extending biological adaptations.
Take the sharks' hearts. They pump slowly — about one beat every 12 seconds — and they beat for centuries. Human hearts beat about once a second in adulthood but slow down over time as they stiffen with age.
"Heart disease is a disease of aging," says Holly Shiels, a University of Manchester environmental physiologist who is studying the cardiovascular function of S. microcephalus. "For humans, our likelihood of having any type of heart disease rockets up each year we live beyond the age of 65. So how do these shark hearts continue beating, in some cases for more than 500 years?"
To find out, scientists at the University of Manchester and the University of Copenhagen recently spent several months in the Arctic, extracting hearts from Greenland sharks that had died after being trapped in fishermen's nets. Over the next year, the researchers will examine the specimens with MRI scans, mass spectrometry, and other techniques to identify any molecules that seem to protect the cardiovascular tissue.
"No one has studied Greenland shark hearts before, so we're hoping to find some completely new drug targets," Shiels says. "If we discover pathways which prevent the heart from changing form and function with age, we can then try to develop drugs which mimic this process in humans. This may be beneficial for people particularly at risk of heart problems due to family history."
Different Immune Systems
In addition to resilient hearts, Greenland sharks seem to have an extremely low risk for cancer and infectious diseases — and the explanation for that may lie with their unusual immune system.
Most of the white cells that are a key component of the human immune system — and which gobble up cancer cells and harmful pathogens as fast as they can — are produced within our bone marrow. The Greenland shark has no bone marrow, and no white cells. How can their bodies fight off these threats?
At the Arctic University of Norway, researchers are sequencing samples of DNA taken from the fins of 100 Greenland sharks that are at least 300 years old. They intend to compare the sharks' DNA with that of other shark species to identify genetic mutations that help stop cancer cells and fight off bacterial and viral invaders.
"We're particularly interested in a family of genes called the major histocompatibility complex," says Kim Praebel, professor of marine ecology at the university and the leader of the research. "The more combinations of gene mutations you have in this family, the stronger your immune system is, and we're searching for particular combinations which are only found in Greenland sharks that live for hundreds of years."
If researchers do tie the shark's reduced risk of disease to specific gene mutations, it might be possible to develop drugs that would mimic the effects of the mutations. Another possibility would be to use a gene-editing tool like CRISPR to modify analogous genes in our own bodies so that they too have the beneficial mutations.
"These genetic manipulation approaches using stem cells are already possible," says the University of Liverpool's Joao Magalhaes, a noted researcher on aging. "As we discover more anticancer or immune-boosting mechanisms in other species like these sharks, we may be able to convert them into therapies in the next few years."
Transplanting Shark Genes
In a decade or so, gene therapy techniques may be advanced enough that we could simply add beneficial shark genes to the human genome. Thus we may modify our bodies so that we avoid disease and have longer lives in exactly the way the sharks do.
The first step will be to insert the beneficial genes into mice and to observe the effect. If the results of this research are promising, research involving humans will follow.
"One of the possible approaches would be to use a virus to introduce the new genes into the cells of the individual through a viral infection," says Magalhaes. "Right now this is still an emerging technology, and there's lots of challenges. Sometimes the body's immune system responds to the virus and that causes problems, but in the future, our capacity to modify the human genome in this way is going to increase significantly."
Complex social, economic, and environmental challenges would no doubt arise if humans were to start living significantly longer lives. Yet it seems inevitable that in coming years scientists will continue to study the sharks, along with other long-lived animals, to see if it might be possible to reprogram our bodies' cells to make advantageous adaptations from these creatures our own.