ABSTRACT
More than four decades ago, Hayflick and colleagues formally showed that
normal human cells-in this case, fibroblasts from fetal and adult tissue-have
only a limited ability to divide in culture (1,2). These now classic studies
established that freshly explanted human fibroblasts initially proliferate robustly
in culture; however, with each passage, the cultures gradually accumulate viable
but nondividing cells. Eventually, the cultures become entirely postmitotic
(incapable of proliferation), despite optimal culture conditions. This decline in
proliferative capacity was termed cellular senescence because it was proposed to
recapitulate the loss of regenerative capacity that is a hallmark of organismal
aging.