Elevated mtDNA content in RBCs promotes oxidative stress may be responsible for faster senescence in men

Both we and others have found that RBC counts are significantly lower in older compared to younger. However, when gender is factored in, a significant age-related decrease of RBC counts is observed only in men but not in women.

qPCR and confocal microscopy were used to detect the presence of mtDNA in RBCs. Flow cytometry and specific inhibitors were used to determine how RBCs uptake cf-mtDNA. The peripheral blood was collected from 202 young adults and 207 older adults and RBC and plasma were isolated. The levels of TLR9⁺RBCs and apoptotic RBCs after uptake of cf-mtDNA by RBCs were measured by flow cytometry. The kit detects changes in SOD and MDA levels after cf-mtDNA uptake by RBCs. Young RBCs (YR) and old RBCs (OR) from single individuals were separated by Percoll centrifugation.

We found a significant decrease in RBC counts and a significant increase in the RDW with aging only in men. We also found that significantly elevated mtDNA content in RBCs was observed only in men during aging and was not found in women. Further studies demonstrated that RBCs could take up cf-mtDNA via TLR9, and the uptake of mtDNA might lead to a decrease in the RBC number and an increase in RDW due to an increase of oxidative stress.

The RBC mtDNA content might be a potential marker of RBC aging and the elevated RBC mtDNA content might be the cause of faster senescence in males than females.