Individuals who demonstrate exceptional longevity are proof that people can live longer, healthier lives. Centenarians (over 100 years old) provide a unique lens through which to study longevity and healthy aging, as they have the ability to delay or escape aging-related diseases such as cancer, cardiovascular disease, and Alzheimer’s disease. while disability is clearly avoided. Problematically, models of human aging and resilience to diseases that allow testing of potential interventions are virtually non-existent.
In an effort to solve this problem, researchers from Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center (BMC) have created the world’s largest library of induced pluripotent stem cells (iPSCs) from centenarians and their descendants. iPSCs can be grown indefinitely, differentiated into any cell or tissue type in the body, and faithfully record the genetic background of the person from whom they were created.
By creating centenarian stem cells, we hope to decipher how these individuals delay or avoid age-related diseases and, in the same capacity, develop and/or validate therapies. This research provides a unique resource that can be used to better understand the mechanisms behind centennial resilience and help others maximize their healthy years of life.”
Todd Dowrey, first author, a PhD candidate in the department of molecular and translational medicine, Boston University School of Medicine
The researchers obtained and characterized more than 100 peripheral blood samples from centenarians and descendants, including those containing data on their resistance to disability and cognitive impairment. The team analyzed how gene expression is regulated in molecular aging clocks to compare and contrast the differences between biological and chronological age in these specialized subjects. Isolated peripheral blood mononuclear cells were then successfully reprogrammed into high-quality iPSC lines that were functionally characterized for pluripotency, genomic stability, and the ability to develop and differentiate into multiple cell types.
Additionally, the researchers found that centenarians and their offspring showed significantly younger biological ages. Some individuals showed a difference of as much as twenty years in biological versus chronological age.
According to the researchers, this work highlights the significant, growing connection between regenerative medicine and aging biology. “By harnessing our ability to study the resilience of centenarians ‘in a dish,’ we hope to unlock a detailed roadmap to healthy living, disease resistance and longevity,” said corresponding author George J. Murphy, PhD, University associate professor of medicine at the school and co-founder of the BU and BMC Center for Regenerative Medicine (CReM).
CReM brings together nine principal investigators working on various aspects of developmental biology, stem cells, regeneration and injury, cell lineage specification and disease modeling, with a key focus on iPSCs.
“Our participants are always incredibly generous and without them we wouldn’t be able to conduct these unique studies. In turn, we hope to cement their legacy, as the stem cell lines we create from them will last forever and be used by researchers around the world. world,” added study co-author Thomas T. Perls, MD, professor of medicine and founding director of the school’s New England Centenarian Study.
The study appears online in the journal Aging Cell.
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Magazine reference:
Dowrey, T.W. et al. (2024) A lifespan-specific bank of induced pluripotent stem cells from centenarians and their offspring. Aging cell. doi.org/10.1111/acel.14351.