Changes of serum‐induced ornithine decarboxylase activity and putrescine content during aging of IMR‐90 human diploid fibroblasts

The roles of ornithine decarboxylase (ODC, EC 4.1.1.17) and polyamines in cellular aging were investigated by examining serum‐induced changes of these parameters in quiescent IMR‐90 human diploid fibroblasts as a function of their population doubling level (PDL) and in human progeria fibroblasts. Serum stimulation caused increases of ODC and DNA synthesis in IMR‐90 human diploid fibroblasts, with maximal values occurring, respectively, 10 hr and 22 hr after serum stimulation. Both serum‐induced ODC activity and DNA synthesis in IMR‐90 cells were found to be inversely related to their PDL. Maximal ODC activity and DNa synthesis in young cells (PDL = ∼ 18–22) were, respectively, five‐fold and six‐fold greater than that in old cells (PDL = ∼ 50–55), which in turn were comparable or slightly higher than that in progeria fibroblasts. Polyamine contents (putrescine, spermidine, and spermine) in quiescent IMR‐90 cells did not show significant PDL‐dependency. The putrescine and spermine contents in quiescent progeria cells were comparable to those in quiescent IMR‐90 cells. The spermidine content in quiescent progeria cells, however, was extremely low, less than half of that in quiescent IMR‐90 cells. Serum stimulation caused a marked increase in putrescine content in young cells but not in old cells or in progeria cells. The spermidine and the spermine content in IMR‐90 cells, either young or old, and in progeria cells did not change significantly after serum stimulation. Our study indicated that aging of IMR‐90 human diploid fibroblasts was accompanied by specific changes of polyamine metabolism, namely, the serum‐induced ODC activity and putrescine accumulation. These changes were also observed in progeria fibroblasts derived from patients with Hutchinson‐Cilford syndrome.