Department of Biochemistry, Aging and Physical Culture Research Institute, Seoul National University College of Medicine, Seoul, 110-799, Korea
We observed that the transglutaminase (tTGase) level and activity
increased in aged rats and senescent primary fibroblasts, suggesting
that the tTGase-mediated macromolecule crosslinking may play
a mechanistic role during aging. Although preliminary, our
in vitro experiment suggests that the target of tTGase is core
histones: H2A:H2B and H3:H4 are specifically crosslinked by
tTGase. On the basis of these data, we postulate that the changes
of DNA metabolism in association with cellular aging may be
ascribed primarily to the crosslinking of core histone subunits.
Further speculation awaits substantive data showing increased
histone crosslinking in senescent cells and also what crosslinked
histones in various DNA metabolisms may imply. At the moment,
present data are sufficient to propose that tTGase is a senescence
marker and it may be primarily responsible for the phenotypes
associated with cellular senescence.
