A longevity-specific bank of induced pluripotent stem cells from centenarians and their offspring

Author:

Dowrey Todd W.ORCID,Cranston Samuel F.,Skvir NicholasORCID,Lok Yvonne,Gould Brian,Petrowitz Bradley,Villar Daniel,Shan Jidong,James Marianne,Dodge Mark,Belkina Anna C.ORCID,Giadone Richard M.ORCID,Sebastiani Paola,Perls Thomas T.,Andersen Stacy L.,Murphy George J.ORCID

Abstract

ABSTRACTCentenarians provide a unique lens through which to study longevity, healthy aging, and resiliency. Moreover, models ofhumanaging and resilience to disease that allow for the testing of potential interventions are virtually non-existent. We obtained and characterized over 50 centenarian and offspring peripheral blood samples including those connected to functional independence data highlighting resistance to disability and cognitive impairment. Targeted methylation arrays were used in molecular aging clocks to compare and contrast differences between biological and chronological age in these specialized subjects. Isolated peripheral blood mononuclear cells (PBMCs) were then successfully reprogrammed into high-quality induced pluripotent stem cell (iPSC) lines which were functionally characterized for pluripotency, genomic stability, and the ability to undergo directed differentiation. The result of this work is a one-of-a-kind resource for studies of human longevity and resilience that can fuel the discovery and validation of novel therapeutics for aging-related disease.

Publisher

Cold Spring Harbor Laboratory

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