Anti-Aging Effect of Urolithin A on Bovine Oocytes In Vitro

Fonseca, Élisa; Marques, C.C.; Pimenta, Jorge; Jorge, Joana; Baptista, M.C.; Gonçalves, Ana Cristina; Pereira, Manuel F. O. Seabra

doi:10.3390/ani11072048

Cited by 7 publications

(4 citation statements)

References 64 publications

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“…Further, Urolithin A has been found to be safe and effective in humans and improves muscle strength [53,60]. A recent 'in vitro aging' study of bovine oocytes suggests that UA may be beneficial for mammalian in vitro ART applications [61]. Our in vivo studies of reproductive aging suggest that UA may improve reproductive span with age by promoting maintenance of oocyte quality, supporting our model that mitophagy may be a key component to combating reproductive decline.…”

Section: Plos Geneticssupporting

confidence: 77%

Oocyte mitophagy is critical for extended reproductive longevity

Cota

Sohrabi²,

Kaletsky³

et al. 2022

PLoS Genet

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Women’s reproductive cessation is the earliest sign of human aging and is caused by decreasing oocyte quality. Similarly, C. elegans’ reproduction declines in mid-adulthood and is caused by oocyte quality decline. Aberrant mitochondrial morphology is a hallmark of age-related dysfunction, but the role of mitochondrial morphology and dynamics in reproductive aging is unclear. We examined the requirements for mitochondrial fusion and fission in oocytes of both wild-type worms and the long-lived, long-reproducing insulin-like receptor mutant daf-2. We find that normal reproduction requires both fusion and fission, but that daf-2 mutants utilize a shift towards fission, but not fusion, to extend their reproductive span and oocyte health. daf-2 mutant oocytes’ mitochondria are punctate (fissioned) and this morphology is primed for mitophagy, as loss of the mitophagy regulator PINK-1 shortens daf-2’s reproductive span. daf-2 mutants maintain oocyte mitochondria quality with age at least in part through a shift toward punctate mitochondrial morphology and subsequent mitophagy. Supporting this model, Urolithin A, a metabolite that promotes mitophagy, extends reproductive span in wild-type mothers–even in mid-reproduction—by maintaining youthful oocytes with age. Our data suggest that promotion of mitophagy may be an effective strategy to maintain oocyte health with age.

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Section: Plos Geneticssupporting

confidence: 77%

Oocyte mitophagy is critical for extended reproductive longevity

Cota

Sohrabi²,

Kaletsky³

et al. 2022

PLoS Genet

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“…UA has previously been reported to exert anti-aging effects in several cells 27 . UA improves mitochondrial respiratory capacity and induces the expression of mitochondrial oxidative phosphorylation proteins 11 .…”

Section: Discussionmentioning

confidence: 99%

Urolithin A attenuates auditory cell senescence by activating mitophagy

Cho

Song

2022

Sci Rep

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Aging of sensory organs is associated with a decline in mitochondrial function and the accumulation of dysfunctional mitochondria. Impaired mitophagy blocks the turnover of dysfunctional mitochondria and leads to their accumulation. Urolithin A (UA) induces mitophagy in various mammalian cells. This study was aimed at investigating the effect of the mitophagy activator, UA, on premature senescent auditory cells. The levels of cellular senescence-associated p53 and p21 significantly increased in H2O2-induced senescent House Ear Institute‐Organ of Corti 1 (HEI-OC1) cells and cochlear explants. However, the levels of mitophagy-related molecules significantly decreased. UA significantly decreased the expression of senescence-associated p53 and p21, and increased the expression of mitophagy-related proteins, in H2O2-induced senescent cells and cochlear explants. The percentage of β-galactosidase-stained senescent cells also reduced in H2O2-treated cells and cochlear explants upon UA pre-treatment. The formation of mitophagosomes and mitophagolysosomes was restored upon UA pre-treatment of H2O2-induced senescent cells. The knockdown of mitophagy-related genes (Parkin and Bnip3) resulted in annulment of UA-induced anti-senescent activity. UA significantly increased the ATP content, mitochondrial DNA (mtDNA) integrity, and mitochondrial membrane potential in senescent HEI-OC1 cells. These findings indicate that UA counteracted mitophagy decline and prevented premature senescence in auditory cells. Hence, UA administration might be a promising strategy for preventing mitochondrial dysfunction in patients with age-related hearing loss.

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“…NRF2 localizes around the meiotic spindle and is associated with the proper formation or stabilization of the spindle, and its expression is significantly decreased in aged oocytes, resulting in the loss of GSH synthesis [33]. In addition, accumulating studies have indicated that the activation of NRF2 signaling could be a potential regulator to suppress oxidative stress to normalize reproductive functions [34,35].…”

Section: Discussionmentioning

confidence: 99%

The Antioxidant Auraptene Improves Aged Oocyte Quality and Embryo Development in Mice

et al. 2022

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Decrease in quality of postovulatory aged oocytes occurs due to oxidative stress and leads to low fertilization and development competence. It is one of the main causes that exerting detrimental effect on the success rate in assisted reproductive technology (ART). Auraptene (AUR), a citrus coumarin, has been reported to possess an antioxidant effects in other tissues. In this study, we aimed to confirm the potential of AUR to delay the oocyte aging process by alleviating oxidative stress. Superovulated mouse oocytes in metaphase of second meiosis (MII) were exposed to 0, 1 or 10 μM AUR for 12 h of in vitro aging. AUR addition to the culture medium recovered abnormal spindle and chromosome morphology and mitigated mitochondrial distribution and mitochondrial membrane potential (ΔΨ) in aged oocytes. AUR-treated aged oocytes also showed suppressed oxidative stress, with lower reactive oxygen species (ROS) levels, higher glutathione (GSH) levels and increased expression of several genes involved in antioxidation. Furthermore, AUR significantly elevated the fertilization and embryo developmental rates. Oocytes aged with 1 μM AUR exhibited morphokinetics that were very similar to those of the control group. Altogether, these data allowed us to conclude that AUR improved the quality of aged oocytes and suggest AUR as an effective clinical supplement candidate to prevent postovulatory aging.

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Anti-Aging Effect of Urolithin A on Bovine Oocytes In Vitro

Cited by 7 publications

References 64 publications

Oocyte mitophagy is critical for extended reproductive longevity

Oocyte mitophagy is critical for extended reproductive longevity

Urolithin A attenuates auditory cell senescence by activating mitophagy

The Antioxidant Auraptene Improves Aged Oocyte Quality and Embryo Development in Mice

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