A newly developed resource enables research into human longevity and resilience, potentially leading to the creation and validation of new treatments for age-related diseases.
People who exhibit extraordinary longevity provide insight into how humans can enjoy longer, healthier lives. Centenarians—those over 100 years old—afford a unique perspective for studying longevity and healthy aging, as they often manage to postpone or evade age-related illnesses such as cancer, heart disease, and Alzheimer’s while significantly reducing their chances of becoming disabled. Unfortunately, there are hardly any models of human aging and disease resilience that allow for testing possible treatments.
To address this gap, researchers at Boston University’s Chobanian & Avedisian School of Medicine and Boston Medical Center have assembled the world’s largest collection of induced pluripotent stem cells (iPSCs) derived from centenarians and their descendants. iPSCs can proliferate indefinitely and can be transformed into any type of cell or tissue, while effectively preserving the genetic profile of the original donor.
“By generating stem cells from centenarians, we aim to uncover how these individuals manage to delay or steer clear of age-related diseases, and to develop and validate medical treatments related to this. This research offers a valuable resource to enhance our understanding of how centenarians maintain their resilience and assist others in maximizing their healthy lifespan,” said lead author Todd Dowrey, a PhD candidate in the molecular & translational medicine department at the school.
The research team analyzed and categorized over 100 blood samples from centenarians and their descendants, including data concerning their resilience against disability and cognitive decline. They examined how gene expression is controlled in molecular aging clocks to explore the differences between biological and chronological age among these unique subjects. The team successfully reprogrammed isolated peripheral blood mononuclear cells into top-quality iPSC lines, which were analyzed for features like pluripotency, genomic stability, and potential to differentiate into various cell types.
Moreover, the researchers found that centenarians and their descendants exhibited notably younger biological ages, with some individuals showing a disparity of up to 20 years between biological and chronological age.
This research underscores the growing link between regenerative medicine and the biology of aging. “By leveraging our ability to study the resilience of centenarians ‘in vitro’, we aspire to unlock a comprehensive guide to healthy living, disease resistance, and longevity,” stated corresponding author George J. Murphy, PhD, 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 who study different facets of developmental biology, stem cells, regeneration and injury, lineage specification, and disease modeling, focusing primarily on iPSCs. Learn more about CReM here.
“Our study participants are incredibly generous, and without their cooperation, we couldn’t conduct these pioneering studies. We hope to honor their legacy by ensuring that the stem cell lines derived from them endure and are utilized by researchers globally,” remarked co-author Thomas T. Perls, MD, professor of medicine and founding director of the New England Centenarian Study at the school.
The findings have been published online in the journal Aging Cell.
GJM, TP, PS, and SA receive funding from NIH-NIA (UH3 AG064704) and U19 AG073172).
