Partial Reprogramming as a Method for Regenerating Neural Tissues in Aged Organisms

Cell Reprogram. 2024 Feb;26(1):10-23. doi: 10.1089/cell.2023.0123.

Abstract

Aging causes numerous age-related diseases, leading the human species to death. Nevertheless, rejuvenating strategies based on cell epigenetic modifications are a possible approach to counteract disease progression while getting old. Cell reprogramming of adult somatic cells toward pluripotency ought to be a promising tool for age-related diseases. However, researchers do not have control over this process as cells lose their fate, and cause potential cancerous cells or unexpected cell phenotypes. Direct and partial reprogramming were introduced in recent years with distinctive applications. Although direct reprogramming makes cells lose their identity, it has various applications in regeneration medicine. Temporary and regulated in vivo overexpression of Yamanaka factors has been shown in several experimental contexts to be achievable and is used to rejuvenate mice models. This regeneration can be accomplished by altering the epigenetic adult cell signature to the signature of a younger cell. The greatest advantage of partial reprogramming is that this method does not allow cells to lose their identity when they are resetting their epigenetic clock. It is a regimen of short-term Oct3/4, Sox2, Klf4, and c-Myc expression in vivo that prevents full reprogramming to the pluripotent state and avoids both tumorigenesis and the presence of unwanted undifferentiated cells. We know that many neurological age-related diseases, such as Alzheimer's disease, stroke, dementia, and Parkinson's disease, are the main cause of death in the last decades of life. Therefore, scientists have a special tendency regarding neuroregeneration methods to increase human life expectancy.

Keywords: aging; cell reprogramming; epigenetics; neuron regeneration; partial reprogramming.

Publication types

  • Review

MeSH terms

  • Adult
  • Aged
  • Aging*
  • Alzheimer Disease*
  • Animals
  • Cell Transformation, Neoplastic
  • Cellular Reprogramming
  • Epigenesis, Genetic
  • Humans
  • Mice