A longevity-specific bank of induced pluripotent stem cells from centenarians and their offspring.
Todd W DowreySamuel F CranstonNicholas SkvirYvonne LokBrian GouldBradley PetrowitzDaniel VillarJidong ShanMarianne JamesMark DodgeAnna C BelkinaRichard M GiadonePaola SebastianiThomas T PerlsStacy L AndersenGeorge F MurphyPublished in: bioRxiv : the preprint server for biology (2024)
Centenarians provide a unique lens through which to study longevity, healthy aging, and resiliency. Moreover, models of human aging 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.
Keyphrases
- induced pluripotent stem cells
- stem cells
- endothelial cells
- peripheral blood
- cognitive impairment
- high fat diet
- small molecule
- climate change
- magnetic resonance
- high glucose
- drosophila melanogaster
- physical activity
- multiple sclerosis
- palliative care
- electronic health record
- genome wide
- pluripotent stem cells
- machine learning
- high throughput
- type diabetes
- insulin resistance
- oxidative stress
- big data
- magnetic resonance imaging
- single cell
- stress induced
- data analysis