Methods and compositions for rejuvenating CNS glial populations by suppresion of transcription factors

A method of suppressing expression of either CDKN1A/p21 or CDKN2A/p16, or both in a population of adult glial progenitor cells, said method comprising:

• administering, to the population of adult glial progenitor cells, an agent that suppresses one or more transcription factors, wherein the one or more transcription factors are selected from zinc finger protein 274 (ZNF274) and E2F transcription factor 6 (E2F6),
• wherein the agent comprises one or more nucleic acid molecules that comprise a first nucleic acid sequence encoding a Cas protein and a second nucleic acid sequence encoding a guide RNA comprising a nucleotide sequence that is complementary to a portion of a gene encoding one or more of the transcription factors;
• and
• wherein the nucleotide sequence of the guide RNA is complementary to an E2F6 gene of Accession No:
• NM 001278277.2 or is complementary to a ZNF274 gene of Accession No:
• XR 001753588.2, wherein the guide RNA is 5 to 100 nucleic acid residues in length.