When Jeanne Calment died on the age of 122, her longevity had researchers scratching their heads. Although physically lively for many of her life, she was also a daily smoker and enjoyed wine—lifestyle decisions which might be generally thought to diminish healthy lifespan.
Teasing apart the intricacies of human longevity is complicated. Weight loss program, exercise, and other habits can change the trajectory of an individual’s health as they get older. Genetics also plays a job—especially throughout the twilight years. But experiments to check these ideas are difficult, partially due to our relatively long lifespan. Following a big population of individuals as they age is prohibitively expensive, and results could take many years. So, most studies have turned to animal aging models—including flies, rodents, and dogs—with far shorter lives.
But what if we could model human “aging in a dish” using cells derived from individuals with exceptionally long lives?
A brand new study, published in Aging Cell, did just that. Leveraging blood draws from the Latest England Centenarian Study—the biggest and most comprehensive database of centenarians—they transformed blood cells into induced-pluripotent stem cells (iPSCs).
These cells contain their donor’s genetic blueprint. In essence, the team created a biobank of cells that might aid researchers of their seek for longevity-related genes.
“Models of human aging, longevity, and resistance to and/or resilience against disease that allow for the functional testing of potential interventions are virtually non-existent,” wrote the team.
They’ve already shared these “super-aging” stem cells with the remainder of the longevity community to advance understanding of the genes and other aspects contributing to a healthier, longer life.
“This bank is actually exciting,” Chiara Herzog, a long life researcher at Kings College London, who was not involved within the study, told Nature.
Precious Resource
Centenarians are rare. In response to the Pew Research Center, based on data from the US Census Bureau, they make up only 0.03 percent of the country’s population. Across the globe, roughly 722,000 people have celebrated their one centesimal birthday—a tiny fraction of the over eight billion people currently on Earth.
Centenarians don’t just live longer. They’re also healthier, even in extreme old age, and fewer more likely to suffer age-related diseases, corresponding to dementia, Type 2 diabetes, cancer, or stroke. Some evade these dangerous health problems altogether until the very end.
What makes them special? Within the last decade, several studies have begun digging into their genes to see that are lively (or not) and the way this pertains to healthy aging. Others have developed aging clocks, which use myriad biomarkers to find out an individual’s biological age—that’s, how well their bodies are working. Centenarians regularly stood out, with a genetic landscape and bodily functions resembling people far younger than expected for his or her chronological age.
Realizing the potential for studying human aging, the Latest England Centenarian Study launched in 1995. Now based at Boston University and led by Tom Perls and Stacy Andersen, each authors of the brand new study, the project has recruited centenarians through quite a lot of methods—voter registries, news articles, or mail to elderly care facilities.
Because longevity could have a genetic basis, their children were also invited to hitch, with spouses serving as controls. All participants reported on their socioeconomic status and medical history. Researchers assessed their cognition on video calls and screened for potential mental health problems. Finally, some participants had blood samples taken. Despite their age, many centenarians remained sharp and will deal with themselves.
Super-Ager Stem Cells
The team first tested participants with quite a lot of aging clocks. These measured methylation, which shuts genes down without changing their DNA sequences. Matching previous results, centenarians were, on average, six and a half years younger than their chronological age.
The anti-aging boost wasn’t as distinguished of their children. Some had higher biological ages and others lower. This might be due to variation in who inherited a genetic “signature” related to longevity, wrote the team.
They then transformed blood cells from 45 centenarians into iPSCs. The people they selected were “on the extremes of health and functionality,” the team wrote. Due to their age, they initially expected that turning back the clock may not work on old blood cells.
Luckily, they were fallacious. Several proteins showed the iPSCs were healthy and capable of creating other cells. In addition they mostly maintained their genomic integrity—although surprisingly, cells from three male centenarians showed a slight lack of the Y chromosome.
Previous studies have found the same deletion pattern in blood cells from males over 70 years of age. It might be a marker for aging and a possible risk factor for age-related conditions corresponding to cancer and heart disease. Women, on average, live longer than men. The findings “allow for interesting research opportunities” to raised understand why Y chromosome loss happens.
Unraveling Aging
Turning blood cells into stem cells erases signs of aging, especially those related to the cells’ epigenetic state. This controls whether genes are turned on or off, and it changes with age. However the underlying genetic code stays the identical.
If the secrets to longevity are, even only partially, hidden within the genes, these super-aging stem cells could help researchers determine what’s protective or damaging, in turn prompting latest ideas that slow the ticking of the clock.
In a single example, the team nudged the stem cells to change into cortical neurons. These neurons form the outermost a part of the brain liable for sensing and reasoning. They’re also the primary to decay in dementia or Alzheimer’s disease. Those derived from centenarians higher fought off damage, corresponding to rapidly limiting the spread of toxic proteins that accumulate with age.
Researchers are also using the cells to check for resilience against Alzheimer’s. One other experiment observed cell cultures made from healthy neurons, immune cells, and astrocytes. The latter, supporting cells that help keep brains healthy, were created using centenarian stem cells. Astrocytes have increasingly been implicated in Alzheimer’s, but their role has been hard to check in humans. Those derived from centenarian stem cells offer a way forward.
Each line of centenarian stem cells is linked to its donor—their demographics, cognitive, and physical state. This extra information could guide researchers in selecting one of the best centenarian cell line for his or her investigations into different facets of aging. And since the cells might be transformed right into a wide selection of tissues that decline with age—muscles, heart, or immune cells—they provide a brand new option to explore how aging affects different organs, and at what pace.
“The results of this work is a one-of-a-kind resource for studies of human longevity and resilience that may fuel the invention and validation of novel therapeutics for aging-related disease,” wrote the authors.
