Cellular Reprogramming, Transdifferentiation and Alleviation of the Aging Pathology

Abstract

Cellular reprogramming and transdifferentiation have emerged as transformative technologies in regenerative medicine, holding significant promise for addressing age-related pathologies and rare genetic disorders. Dr. Shinya Yamanaka's pioneering work in cellular reprogramming paved the way for the restoration of pluripotency in terminally differentiated cells. The understanding that exogenous introduction of the key transcription factors (Oct4, Sox2, KLF4 and c-Myc) enables cells for reprogramming, regaining pluripotency has provided tremendous opportunities and better platforms for therapeutic implications. Transdifferentiation, the conversion of one differentiated cell type to another, offers a complementary approach to cellular reprogramming and can be procured by modulating the expression of specific transcription factors, miRNAs, or other small molecules. Therapeutic approaches that utilize transdifferentiated cells are promising in addressing the age-related pathologies of vital organs such as the pancreas, liver, cardiovascular system as well as neurological disorders. Additionally, the emerging field of epigenetic rejuvenation offers extended possibilities for targeted interventions as it focuses on targeting age-associated CpG signatures of the epigenome. Induced pluripotent stem cells (iPSCs) obtained by cellular reprogramming have become invaluable tools for studying rare monogenic syndromes and premature aging diseases that include Hutchinson-Gilford Progeria Syndrome (HGPS) and Werner syndrome. iPSCs enable researchers to model diseases and gain insights into their underlying mechanisms. Translation of these technologies into clinical practice just needs bypassing hurdles related to safe, efficient, specific therapeutic outcomes. Thus, recent advancements in stem cell technologies highlight that cellular reprogramming and transdifferentiation are poised to revolutionize healthcare, providing novel approaches to address age-related pathologies and other genetic disorders.