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.