Older infertility patients have reduced oocyte mitochondrial production of ATP, which limits normal oocyte chromosomal disjunction and subsequent embryo development. Coenzyme Q10 (CoQ10) is a crucial substrate in the electron transport chain of mitochondria. The cumulus cells (CC), which nourish the oocyte, can produce and deliver CoQ10 to the oocyte like other substrates including cholesterol. The objective of the present study was to evaluate whether CoQ10 synthesis and mitochondrial activity in CC is altered with aging in mice, and if CoQ10 supplementation would improve CC mitochondrial function. Case-control study. 10 aged (12 months) and 10 young ICR mice (2-3 months) were superovulated and retrieved oocytes were stripped of CC. Another 10 aged mice were injected with coQ10 in oil (70 mg/week SC for 12 weeks). The CC from each oocyte were counted and examined by TUNEL for apoptosis, by RT-PCR for genes in the CoQ10 synthesis pathway, and by mitotracker green and red for mitochondrial content and activity. The number of CC per oocyte was decreased with aging (3050±236 young vs 1472±143 aged; P<0.001) and was abrogated (2218±276) in the aged-CoQ10 treated group. We saw a significant increase in apoptotic CC with aging (9.3% young vs 14.2% old; P<0.05, that was completely reversed by CoQ10 (6.9%). The expression of coQ10 synthesis genes was reduced in the aged compared to young animals, with significant reduction in Coq6 and Pdss2 (P<0.008 and P<0.013, respectively). Preliminary results showed reduced levels of CC mitochondrial content and activity with aging. Reduced CoQ10 synthesis gene expression was found in CC and was associated with decreased CC number, increased apoptosis, and decreased mitochondrial energy. Our results support reduced substrate synthesis in CC as a factor in reproductive aging in mammals. We are presently analyzing expression of CoQ10 synthesis genes in CC of older women undergoing IVF/ICSI and measuring coQ10 levels in follicular fluid.