Scientists Have Reset Cells From a Supercentenarian, Giving Clues to Their Extreme Longevity
Scientists have taken cells from a 114-year-old and reprogrammed them to be stem cells, effectively resetting the age to zero. The experiment could open the door to new fields of research relating to the aging process, researchers say.
Supercentenarians are people who live beyond the age of 110. Studying these people is of interest to scientists as not only do they live longer than the vast majority of people, they appear to stay healthy for far longer too. According to the Gerontology Research Group, which tracks supercentenarians, there are just 56 people in the world alive today who are verified as being over 110 years old.
Researchers trying to find shared characteristics of people who live to this extreme old age have found a number of common traits. One study from 2008 looking at supercentenarians in Japan found they have little to no history of cardiovascular disease, and no history of cancer or diabetes. Most were able to continue with normal daily activities until they were 100, but started to become more frail from around 105.
Of the people who live to become a centenarian, only a very small proportion make it another 10 years to become a supercentenarian. What allows them to live this extra decade is unknown.
In a study published in Biochemical and Biophysical Research Communications, researchers based in California attempted to reprogram the blood cells of a 114-year-old woman.
"We set out to answer a big question: Can you reprogram cells this old?" study author Evan Y. Snyder, director of the Center for Stem Cells and Regenerative Medicine at Sanford Burnham Prebys in California, said in a statement.
Cell reprogramming involves reverting mature, specialist cells into pluripotent stem cells. It was developed by Shinya Yamanaka from Japan's Kyoto University in 2006. He created induced pluripotent stem cells from mouse skin cells. These cells could then be used to make any of the tissues in the body.
As well as the 114-year-old, the team, led by Jieun Lee AgeX Therapeutics Inc., also reprogrammed the cells of a health 43-year-old and an eight-year-old with a condition that causes rapid aging. Being able to transform stem cells from supercentenarians could offer an insight into how they live so long.
Their findings showed the supercentenarian cells could be reprogrammed as easily as the cells from the other two subjects. They also found that in some experiments telomeres, which protect the ends of chromosomes from deterioration, but also shorten over time as cells divide, were reset by reprogramming. This meant that effectively, they went from being 114 to zero. Not all telomeres reset, however, suggesting aging does have lasting effects on cells.
Researchers believe that by turning supercentenarian cells back to stem cells, they will be able to work out what allows them to live such long and healthy lives. They hope to look at different types of cells to see if there are any processes unique to this group. "Now we have shown it can be done, and we have a valuable tool for finding the genes and other factors that slow down the aging process," Snyder said in a statement. "Why do supercentenarians age so slowly? We are now set to answer that question in a way no one has been able to before."
Stem cell scientist Peter Rugg-Gunn, from the Babraham Institute, a life sciences research institution in the U.K., said the interest in supercentenarians comes from the potential to uncover ways to extend human lifespan. Rugg-Gunn, who was not involved in the latest study, said the finding that the reset supercentenarian cells were almost indistinguishable from the other cells of younger people was interesting.
"This tells us that there is probably no upper age barrier for cells to undergo reprogramming when given the appropriate conditions, and that cells do not accumulate sufficient damage over a long life that would completely prevent their ability to reprogram," he told Newsweek.
Rugg-Gunn said cells from additional supercentenarians will need to be examined to extend the findings. "Nevertheless, one interesting feature of the research is that the starting donor cells showed consistent differences in the activity of a fairly large number of genes, but these differences disappeared after reprogramming," he said. "This observation implies that genes that are potentially misregulated in aging could be amenable to some sort of correction under certain conditions.
"This may not be so straightforward though because other biological measures of aging, such as the length of chromosome ends called telomeres, were much more variable. In one experiment, telomeres in supercentenarian cells were lengthened as would be predicted from reversing the aging process after reprogramming. In two other experiments using the same donor cells, however, telomere length was not rejuvenated. These findings suggest that there are hurdles to reversing the aging process that we still do not fully understand. One exciting future research direction is to define whether there are pathways that can be targeted in aging to partially restore the cell's function and improve health as we age."
Joao Passos, who studies cells in aging and age-related disease at the Mayo Clinic and was also not involved in the research, told Newsweek the study was interesting, but "not conceptually novel."
However, he added: "As far as I understand, the novelty of the paper... lies in the fact that it shows that there is feasibility in reprogramming of banked...cell lines derived from donors and that it is possible to do so in extreme aged individuals." He added: "The applicability of such strategies to combat aging and age-related disease are still in its infancy."
