Post-translational epigenetic modifications take place in mouse neurons of the dentate gyrus (DG) with age. Here, we report that agedependent reduction in H3K9 trimethylation (H3K9me3) is prevented by cyclic induction of the Yamanaka factors used for cell reprogramming. Interestingly, Yamanaka factors elevated the levels of migrating cells containing the neurogenic markers doublecortin and calretinin, and the levels of the NMDA receptor subunit GluN2B. These changes could result in an increase in the survival of newborn DG neurons during their maturation and higher synaptic plasticity in mature neurons. Importantly, these cellular changes were accompanied by an improvement in mouse performance in the object recognition test over long time. We conclude that transient cyclic reprogramming in vivo in the central nervous system could be an effective strategy to ameliorate aging of the central nervous system and neurodegenerative diseases.

Human tauopathies, such as Alzheimer's disease (AD), have been widely studied in transgenic mice overexpressing human tau in the brain. The longest brain isoforms of Tau in mice and humans show 89% amino acid identity; however, the expression of the isoforms of this protein in the adult brain of the two species differs. Tau 3R isoforms are not present in adult mice. In contrast, the adult human brain contains Tau 3R and also Tau 4R isoforms. In addition, the N-terminal sequence of Tau protein in mice and humans differs, a Tau peptide (residues 17-28) being present in the latter but absent in the former.Here we review the main published data on this N-terminal sequence that suggests that human and mouse Tau proteins interact with different endogenous proteins and also show distinct secretion patterns.