% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Falckenhayn:289032,
      author       = {C. Falckenhayn and A. Bienkowska and J. Söhle and K.
                      Wegner and G. Raddatz$^*$ and B. Kristof and D. Kuck and R.
                      Siegner and R. Kaufmann and J. Korn and S. Baumann and D.
                      Lange and A. Schepky and H. Völzke and L. Kaderali and M.
                      Winnefeld and F. Lyko$^*$ and E. Grönniger},
      title        = {{I}dentification of dihydromyricetin as a natural {DNA}
                      methylation inhibitor with rejuvenating activity in human
                      skin.},
      journal      = {Frontiers in aging},
      volume       = {4},
      issn         = {2673-6217},
      address      = {Lausanne},
      publisher    = {Frontiers Media S.A.},
      reportid     = {DKFZ-2024-00564},
      pages        = {1258184},
      year         = {2023},
      note         = {DKFZ-ZMBH Alliance},
      abstract     = {Changes in DNA methylation patterning have been reported to
                      be a key hallmark of aged human skin. The altered DNA
                      methylation patterns are correlated with deregulated gene
                      expression and impaired tissue functionality, leading to the
                      well-known skin aging phenotype. Searching for small
                      molecules, which correct the aged methylation pattern
                      therefore represents a novel and attractive strategy for the
                      identification of anti-aging compounds. DNMT1 maintains
                      epigenetic information by copying methylation patterns from
                      the parental (methylated) strand to the newly synthesized
                      strand after DNA replication. We hypothesized that a modest
                      inhibition of this process promotes the restoration of the
                      ground-state epigenetic pattern, thereby inducing
                      rejuvenating effects. In this study, we screened a library
                      of 1800 natural substances and 640 FDA-approved drugs and
                      identified the well-known antioxidant and anti-inflammatory
                      molecule dihydromyricetin (DHM) as an inhibitor of the DNA
                      methyltransferase DNMT1. DHM is the active ingredient of
                      several plants with medicinal use and showed robust
                      inhibition of DNMT1 in biochemical assays. We also analyzed
                      the effect of DHM in cultivated keratinocytes by array-based
                      methylation profiling and observed a moderate, but
                      significant global hypomethylation effect upon treatment. To
                      further characterize DHM-induced methylation changes, we
                      used published DNA methylation clocks and newly established
                      age predictors to demonstrate that the DHM-induced
                      methylation change is associated with a reduction in the
                      biological age of the cells. Further studies also revealed
                      re-activation of age-dependently hypermethylated and
                      silenced genes in vivo and a reduction in age-dependent
                      epidermal thinning in a 3-dimensional skin model. Our
                      findings thus establish DHM as an epigenetic inhibitor with
                      rejuvenating effects for aged human skin.},
      keywords     = {DNA methylation (Other) / DNAm age clock (Other) / DNMT1
                      inhibition (Other) / dihydromyricetin (Other) / rejuvenation
                      (Other) / skin (Other)},
      cin          = {A130},
      ddc          = {610},
      cid          = {I:(DE-He78)A130-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38500495},
      pmc          = {pmc:PMC10944877},
      doi          = {10.3389/fragi.2023.1258184},
      url          = {https://inrepo02.dkfz.de/record/289032},
}