Establishment of an animal model for human cellular againg

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To clarify the pattern of macaque cellular aging, a total of 40 cultures of Japanese macaque (Macaca fuscata), long-tailed macaque (Macaca fascicularis), bonnet monkey (Macaca radiata) and rhesus macaque (Macacamulatta) were carried out. Adherent cells were isolated from skin, kidney and lung, cultured in RPMI 1640 medium supplemented with 10% FBS, and subcultured until they terminated cell division. In 36 cultures, cells underwent senescence showing lager cell size and decreased saturation density, and then terminated cell division (Mortality stage 1 (M1)) at 10-20 Population Doubling Levels (PDLs). Whereas cells in four cultures first exhibited senescent morphology at 15-25 PDLs, but continued cell division through M1 up to 40-100 PDLs and then came into crisis (Mortality stage 2 (M2)). Cells in one culture of Japanese macaque do not terminate cell division (>150 PDLs) and showed several characteristics of transformed cells, such as the anchorage independent growth and loss of contact inhibition. Shortening of telomeres by PDLs and the absence of telomerase activity were identified in all of tested including the transformed one. Macaque cells showed an intermediate pattern of in vitro aging between human and rodent cells, whereas, in terms of telomerase activity, they are relatively close to human cells. It is thus suggested that the macaques serve as animal models for human cellular aging and that they provide us with a key to study possible mechanisms which play roles in the critical stages (M1 and M2) in cellular aging and transformation.