Oxidant-induced macromolecular damage is believed to be an important contributor to aging, which mainly affects postmitotic cells, such as cardiac myocytes and neurons (1). Neonatal rat cardiac myocytes maintained in culture develop progressive senescent-like alterations, similar to those observed in the aging heart in vivo. These changes include the accumulation of functionally effete, often mutant and enlarged mitochondria, as well as the deposition of lipofuscin (age pigment) within the lysosomal compartment. We determined lipofuscin content, mitochondrial membrane potential, and the formation of reactive oxygen species (ROS) in single cultured cardiac myocytes, and also studied the relationship between these parameters. Individual cardiac myocytes showed a linear pattern of lipofuscin accumulation over time. However, the rate of this accumulation varied dramatically between cells. Cells that had accumulated large quantities of lipofuscin usually contained increased numbers of defective mitochondria with low membrane potential and showed high levels of ROS production. The results suggest that oxidative stress, lipofuscin accumulation and mitochondrial damage are interrelated in postmitotic cells and provide further support for the mitochondrial-lysosomal axis theory of aging (2).
1. Harman D. (1956) J. Gerontol., 211: 298-300.
2. Brunk U.T., Terman A. (2002) Eur. J. Biochem., 269: 1996-2002.