Proliferation Cycle Causes Age Dependent Mitochondrial Deficiencies and Contributes to the Aging of Stem Cells

Abstract

In addition to chronological aging, stem cells are also subject to proliferative aging during the adult life span. However, the consequences of proliferative cycle and their contributions to stem cells aging have not been well investigated. Using Drosophila female germ line stem cells as a model, we found that the replication cycle leads to the age dependent decline of female fecundity, and is a major factor causing developmental abnormalities in the progeny of old females. The proliferative aging does not cause telomere shortening, but causes an accumulation of mitochondrial DNA (mtDNA) mutations or rearrangements at the control region. We propose that damaging mutations on mtDNA caused by accumulation of proliferation cycles in aged stem cells may disrupt mitochondrial respiration chain and impair mtDNA replication and represent a conserved mechanism underlying stem cell aging.

Direct Imaging of Lipid Metabolic Changes in Drosophila Ovary During Aging Using DO-SRS Microscopy

“…The continued oocyte production requires consecutive division of the stem cells. The egg production is dramatically decreased during female aging, indicating a significant compromise in the rate of stem cell division ( Ren et al, 2017 ; Dipali et al, 2019 ; Armstrong, 2020 ). Both autonomous signals from a defect in the stem cells and the nonautonomous signals sent to the germ stem cells from the surrounding niche can contribute to replicative senescence ( Narbonne, 2018 ; Sênos Demarco and Jones, 2019 ).…”

Mitochondrial Control of Stem Cell State and Fate: Lessons From Drosophila

“…Preventing mitochondrial fission in aged GSCs enhances their maintenance by preventing their loss due to low mitochondrial membrane potential, decreased ROS levels, and reduced BMP signaling ( Amartuvshin et al, 2020 ). Furthermore, it has been documented that proliferative aging of the GSCs causes dramatic decrease in cytochrome C oxidase activity, impaired mtDNA replication, and accumulation of mutations on mtDNA ( Ren et al, 2017 ). Based on these strong correlations, mitochondrial fission can be considered as an important contributing factor for age-dependent decline in GSC activity, eventually responsible for the reduced hatching rate of embryos produced by old mothers.…”