[A study on alterations in mitochondrial biological characteristics during cellular senescence of human embryonic...

Objective: To study the alterations of mitochondrial biological characteristics during both cellular replicative and premature senescence induced by hydrogen peroxide in human embryonic lung fibroblasts (HEFs). Methods: The premature senescence was induced by 400 μmol/L H(2)O(2) once a day at the same time and with 2 hours each time, after four consecutive days the premature senescence models were classified into premature senescence initiation group (PSi) and premature senescence persistence group (PSp). Based on the life span of HEFs, the cell replicative senescence was divided into five groups included young-age (22 PDL), middle-age (35 PDL), replicative senescence (49 PDL), PSi and PSp. The mitochondrial distribution, relative content, adenosine triphosphate (ATP) contents, 8-hydroxydeoxyguanosine (8-OHdG) levels, the relative mitochondrial transcription factor A (TFAM) as well as mitochondrial DNA methyltransferase 1 (mtDNMT1) mRNA levels, mtDNA copy number, the relative TFAM protein level and the total enzyme activity of mitochondrial DNA methyltransferases (mtDNMTs) were detected in five senescence groups. Results: The mtDNA copy number, 8-OHdG contents, level of mtDNMT1 mRNA and mtDNMTs activity in 49 PDL group were higher than those in 22 PDL group (all P values <0.05); The level of 8-OHdG in PSi was higher than that in 22 PDL group (P<0.05); The ATP contents, mtDNA copy number, the mRNA and protein expression levels of TFAM and mtDNMTs activity of PSp were higher than those in 22 PDL group (all P values<0.05). Conclusion: During the cellular senescence of HEFs, the higher mtDNA copy number and mtDNMTs activity were common features regardless of replicative or premature senescence, with possibility that oxidative stress was involved in modifying the occurrence of premature senescence.