Cell differentiation, aging and cancer: the possible roles of superoxide and superoxide dismutases.

A unified theory of cell differentiation, aging, and cancer is discussed. All cells are hypothesized to originate from stem cells. These stem cells mature as they divide and eventually reach a fully differentiated cell, which cannot divide. Aging is caused by the loss of stem cells, either due to cell death or terminal differentiation, and by eventual death of fully differentiated cells. Both loss of stem cells and death are brought about by oxygen radicals. The cancer phenotype is caused by an inability of a stem cell to differentiate fully under the local environmental conditions. Because the cancer cell cannot differentiate, it never loses its potential for growth. The block in differentiation of cancer cells is caused by a relative lack of radical scavengers, particularly manganese superoxide dismutase, coupled with production of radicals, especially superoxide. The high reactivity of these radicals leads to changes in key subcellular structures and prevents the cell from attaining the organization needed for cell differentiation to occur.