1. Induced pluripotency and spontaneous reversal of cellular aging in supercentenarian donor cells
- Author
-
Paola A. Bignone, Dana Larocca, L.S. Coles, Evan Y. Snyder, Yang Liu, and Ji-Eun Lee
- Subjects
Adult ,0301 basic medicine ,Induced Pluripotent Stem Cells ,Population ,Biophysics ,Clone (cell biology) ,Biology ,Biochemistry ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Progenitor cell ,Child ,education ,Induced pluripotent stem cell ,Molecular Biology ,Cellular Senescence ,Aged, 80 and over ,Progeria ,education.field_of_study ,Mesenchymal stem cell ,Telomere Homeostasis ,Cell Differentiation ,Mesenchymal Stem Cells ,Cell Biology ,Cellular Reprogramming ,medicine.disease ,Tissue Donors ,Clone Cells ,Cell biology ,Telomere ,030104 developmental biology ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,Transcriptome ,Reprogramming - Abstract
Supercentenarians (≥110-year-old, SC) are a uniquely informative population not only because they surpass centenarians in age, but because they appear to age more slowly with fewer incidences of chronic age-related disease than centenarians. We reprogramed donor B-lymphoblastoid cell lines (LCL) derived from a 114-year-old (SC), a 43-year-old healthy disease-free control (HDC) and an 8-year-old with a rapid aging disease (Hutchinson-Gilford progeria syndrome (HGPS)) and compared SC-iPSC to HDC-iPSC and HGPS-iPSCs. Reprogramming to pluripotency was confirmed by pluripotency marker expression and differentiation to 3 germ-layers. Each iPSC clone differentiated efficiently to mesenchymal progenitor cells (MPC) as determined by surface marker expression and RNAseq analysis. We identified supercentenarian and HGPS associated gene expression patterns in the differentiated MPC lines that were not evident in the parental iPSC lines. Importantly, telomere length resetting occurred in iPSC from all donors albeit at a lower incidence in supercentenarian iPSCs. These data indicate the potential to use reprogramming to reset both developmental state and cellular age in the "oldest of the old." We anticipate that supercentenarian iPSC and their differentiated derivatives will be valuable tools for studying the underlying mechanisms of extreme longevity and disease resistance.
- Published
- 2020