Aging in a Dish: iPSC-Derived and Directly Induced Neurons for Studying Brain Aging and Age-Related Neurodegenerative Diseases

Annu Rev Genet. 2018 Nov 23;52:271-293. doi: 10.1146/annurev-genet-120417-031534. Epub 2018 Sep 12.

Abstract

Age-associated neurological diseases represent a profound challenge in biomedical research as we are still struggling to understand the interface between the aging process and the manifestation of disease. Various pathologies in the elderly do not directly result from genetic mutations, toxins, or infectious agents but are primarily driven by the many manifestations of biological aging. Therefore, the generation of appropriate model systems to study human aging in the nervous system demands new concepts that lie beyond transgenic and drug-induced models. Although access to viable human brain specimens is limited and induced pluripotent stem cell models face limitations due to reprogramming-associated cellular rejuvenation, the direct conversion of somatic cells into induced neurons allows for the generation of human neurons that capture many aspects of aging. Here, we review advances in exploring age-associated neurodegenerative diseases using human cell reprogramming models, and we discuss general concepts, promises, and limitations of the field.

Keywords: age-associated neurodegeneration; aging; disease modeling; iNs; iPSCs; induced neurons; induced pluripotent stem cells; rejuvenation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / genetics*
  • Aging / pathology
  • Brain / growth & development
  • Brain / pathology
  • Cellular Reprogramming / genetics
  • Humans
  • Induced Pluripotent Stem Cells / metabolism
  • Induced Pluripotent Stem Cells / pathology*
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / pathology
  • Neurons / metabolism*
  • Neurons / pathology