bims-caglex Biomed News
on Cellular aging and life extension
Issue of 2026–02–15
two papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño
  1. Cognitive rejuvenation through partial reprogramming of engram cells.
  2. Convergence of aging- and rejuvenation-related epigenetic alterations on PRC2 targets.
  1. Neuron. 2026 Feb 10. pii: S0896-6273(25)00925-0. [Epub ahead of print]
    Cognitive rejuvenation through partial reprogramming of engram cells.
    Gabriel Berdugo-Vega, Cesar Sierra, Simone Astori, Veronika Calati, Jules Orsat, Marianne Julie Scoglio, Carmen Sandi, Johannes Gräff.
      Counteracting cognitive decline is a declared goal of regenerative medicine. Recently, partial cellular reprogramming has emerged as a promising strategy to promote tissue regeneration and restore cellular function, but whether this approach bears fruit when targeted to cell populations underlying cognitive processes remains unknown. Here, we report that partial reprogramming of engram neurons-bona fide memory trace cells-by OSK-mediated gene therapy reversed the expression of senescence- and disease-related cellular hallmarks in aged mice and models of Alzheimer's disease (AD), re-established aberrant epigenetic-transcriptional patterns pertaining to synaptic plasticity, and counteracted AD-typical neuronal hyperexcitability. Importantly, irrespective of the brain area targeted or the behavioral paradigm employed, engram reprogramming also recovered learning and memory capacities to levels of healthy young animals, suggesting cognitive rejuvenation. These results posit that partial reprogramming of specific cell populations in the brain can be exploited for cognitive restoration in aging and disease.
    Keywords:  Alzheimer's disease; OSK; age; engram; epigenetic; partial reprogramming; rejuvenation; transcription
    DOI:  https://doi.org/10.1016/j.neuron.2025.11.028
  2. Mol Syst Biol. 2026 Feb 10.
    Convergence of aging- and rejuvenation-related epigenetic alterations on PRC2 targets.
    Oscar Camacho, Michael A Koldobskiy, Pradeep Reddy, Atharv Oak, Yuxiang Sun, Kenna Sherman, Juan Carlos Izpisua Belmonte, Andrew P Feinberg.
      Rejuvenation of tissues in physiologically aging mice can be accomplished by long-term partial reprogramming via expression of reprogramming factors (Oct4, Sox2, Klf4, and c-Myc). To investigate the epigenetic determinants of partial reprogramming-mediated rejuvenation, we used whole-genome bisulfite sequencing to carry out unbiased comprehensive profiling of DNA methylation changes in skin from mice subjected to partial reprogramming, as well as young and untreated old controls. We found a striking convergence of age- and rejuvenation-related epigenetic alterations on targets of the Polycomb repressive complex 2 (PRC2), with increased DNA methylation level and entropy over these regions. Native ChIP demonstrated extensive loss of H3K27me3 in aged epidermis compared to young, partially overlapping regions with age- and rejuvenation-related DNA methylation changes. In addition, large H3K9me2-marked "LOCK" heterochromatin domains defined the boundaries for hypomethylated highly entropic regions during aging. These results are also supported by a likewise prominent enrichment of PRC2 targets in gene expression data, suggesting that PRC2 activity can modulate aging and mediate tissue rejuvenation.
    Keywords:  Aging; DNA Methylation; LOCKs; PRC2; Rejuvenation
    DOI:  https://doi.org/10.1038/s44320-026-00195-9
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