Stem Cells Reveal Secrets of Centenarians

According to a report in Nature magazine, a cell bank composed of cells from people over 100 years old provides scientists with new resources for studying longevity.

Scientists in Boston, Massachusetts, have created reprogrammed stem cells from the blood of centenarians. They plan to share the cells with other researchers to better understand factors that contribute to longevity. Early experiments have already provided insights into brain aging.

Centenarians offer an opportunity to study longevity. People who live to 100 have an amazing ability to recover from injury, says George Murphy, a stem cell biologist at Boston University's Jobanian and Avedisian School of Medicine. One centenarian he knows has recovered from illness twice, once from the Spanish flu in 1912 and again from COVID-19. One theory to explain the robust health of centenarians is that they have a genetic makeup that protects them from disease. But testing that theory is challenging. People of such advanced age are rare, so their blood and skin samples are a valuable resource for research. That gave Murphy and his colleagues the idea to create a bank of centenarian cells that could be shared among scientists.

“This cell bank is really exciting,” says Chiara Herzig, who studies epigenetics and aging at King’s College London.

“It will be a very useful resource for the field,” says Vadim Gladyshev, an aging researcher at Harvard Medical School in Boston.

Searching for centenarians

Murphy worked with Tom Perls, a doctor specializing in geriatrics, also from the Jobanian and Avedisian School of Medicine, who oversees the New England Centenarian Study, the largest study of people aged 100 and older. They looked for centenarians in U.S. voter registration lists, news reports and long-term care facilities. Many of the elderly were happy to participate "because they know how special they are," Perls said. The researchers assessed the participants' cognitive and physical abilities and collected blood samples. Many of the elderly were cognitively healthy and able to take care of themselves.

For about 30 centenarians, the researchers isolated their blood cells and reversed them to a pluripotent state, in which cells can transform into any cell type in the body. Induced pluripotent stem cells (iPS cells) lose many aspects of their "age" during the reversal process without changing their genetic code. This allows researchers to use these cells to study the genetic determinants of aging, Herzig said.

Emerging Insights

Experiments using these cells are already underway. For example, Murphy's team has grown neurons from iPS cells taken from centenarians. One hallmark of aging is that cells lose some of the quality control mechanisms in protein production, which can lead to disease. Unpublished results show that centenarian neurons are more "quiet" under normal circumstances and do not engage in this quality control compared to non-centenarian neurons. However, when a stressor is introduced, the centenarian neurons are able to efficiently and robustly initiate these processes, rapidly separating bad proteins from good proteins at a faster rate.

Another research team created a 3D model of Alzheimer's disease using brain cells from centenarians and compared it with a model made from cells from individuals in their 60s. In preliminary studies, researchers found that brain cells from centenarians expressed high levels of genes associated with protection against Alzheimer's disease, said Do Yeon-jin, a neurology researcher at Harvard Medical School.

Ultimately, the researchers hope to use these cells to develop other cell types associated with aging, such as liver, muscle and intestinal cells, or even mini-organs.