| Transgenic growth hormone mice have many features resembling accelerated aging, but have historically been dismissed as merely pathological. However, enough experimental evidence has accumulated to re-evaluate whether TGM are a valid model of accelerated aging. Dramatic age-related cognitive decline and massive brain cell losses, along with increased incidence of early onset arthritis, cataracts and muscle wasting provide strong evidence to support the re-evaluation. Interestingly, although old TGM do not show elevated lymphocyte apoptosis or increased chromosome aberrations as would be expected with chronic oxidative stress (possibly through the upregulation of cell repair processes), it is apparent that TGM do have much higher levels of accumulated oxidative damage. The significant increase in apoptosis and structural chromosome aberrations after exposure to increased free radicals (i.e. ionizing radiation) in old TGM compared to age-matched normal mice suggests that TGM cells are already at the limit of their ability to cope with the damage produced by their elevated endogenous free radical production. The additional oxidative stress induced by the radiation dose pushes TGM cells over an upper defensive threshold and their cells literally "fall apart". |
