Researchers here stop the reduction in number of sensory cells in the ear, one of the causes of progressive age-related deafness, by slowing the pace of programmed cell death (apoptosis). If employed as a general strategy for reducing losses in any important cell population this will probably lead to an increased risk of cancer: researchers are in effect making damaged cells work for longer. It is unclear at this point as to whether that is either true or a meaningful risk in any specific case, however, especially when small numbers of cells are involved:
Mcl-1 is an anti-apoptotic member of the Bcl-2 family that modulates apoptosis-related signaling pathways and promotes cell survival. We have previously demonstrated a reduction of Mcl-1 expression in aging cochleae. To investigate whether restoring Mcl-1 expression would reduce aging-related cochlear degeneration, we developed a rat model of Mcl-1 overexpression.
A plasmid encoding human Mcl-1/enhanced green fluorescent protein was applied to the round window of the cochlea. This in vivo treatment transfected both the sensory and supporting cells of the cochlear sensory epithelium and enhanced Mcl-1 expression at both the mRNA and the protein level. The upregulation of Mcl-1 expression reduced the progression of age-related cochlear dysfunction and sensory cell death. Furthermore, the transfection of Mcl-1 exerted its protective effect by suppressing cochlear apoptosis at the mitochondrial level. This study demonstrates that the genetic modulation of Mcl-1 expression reduces the progression of age-related cochlear degeneration.