Age-dependent metabolic changes in cultured human fibroblasts

Summary The effects of metabolic poisons on the ATP content of cultured human skin fibroblasts at selected in vitro and in vivo ages were studied. Potassium cyanide, iodacetemide, and Arsenate were used to inhibit ATP restoration by glycolysis and oxidative phosphorylation. Cells treated with these metabolic poisons showed an age-dependent change in their ATP content. The decrease in cellular ATP content after exposure to these drugs was taken as an estimate of ATP turnover. It was found that there was a decrease in the ATP turnover with increasing population doubling level (i.e. in vitro age), and cells cultured from a 68-yr-old donor had a lower ATP turnover than those cultured from a neonatal donor. This decreased ATP turnover correlates with a previous finding of a decreased ability of “older” cells to be stimulated to migrate in culture and suggests that there is a metabolic component to this age-related functional deficiency. This work was supported by National Institutes of Health grants 2, RO1 EY02523 and 1 RO1 1, AGO 1212 awarded to A.L. Muggleton-Harris.