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Urolithin A attenuates auditory cell senescence by activating mitophagy.
Sung Il Cho1, Eu-Ri Jo2, Hansoo Song3
1Department of Otolaryngology-Head and Neck Surgery, Chosun University College of Medicine, 365 Pilmun-daero, Dong-gu, Gwangju, 61453, South Korea. chosi@chosun.ac.kr.
Scientific Reports
|May 13, 2022
Summary
Urolithin A (UA) combats premature aging in auditory cells by enhancing mitophagy, a process that clears damaged mitochondria. This research suggests UA may help prevent age-related hearing loss by restoring mitochondrial function.
Area of Science:
- Cellular Biology
- Mitochondrial Biology
- Otolaryngology
Background:
- Aging sensory organs exhibit mitochondrial dysfunction and impaired mitophagy, leading to the accumulation of damaged mitochondria.
- Premature senescence in auditory cells is linked to decreased mitophagy and increased senescence markers like p53 and p21.
Purpose of the Study:
- To investigate the effects of Urolithin A (UA), a mitophagy activator, on premature senescence in auditory cells.
- To determine if UA can counteract the decline in mitophagy and prevent senescence in cochlear cells.
Main Methods:
- Induced premature senescence in HEI-OC1 cells and cochlear explants using hydrogen peroxide (H2O2).
- Assessed senescence markers (p53, p21, β-galactosidase) and mitophagy-related proteins.
- Evaluated the impact of UA pre-treatment on mitophagy, mitochondrial function (ATP content, mtDNA integrity, membrane potential), and senescence markers.
- Utilized gene knockdown of mitophagy-related genes (Parkin, Bnip3) to confirm UA's mechanism of action.
Main Results:
- UA significantly reduced senescence markers (p53, p21, β-galactosidase) in senescent auditory cells and cochlear explants.
- UA restored the formation of mitophagosomes and mitophagolysosomes, indicating enhanced mitophagy.
- UA improved mitochondrial function by increasing ATP content, mtDNA integrity, and mitochondrial membrane potential.
- The anti-senescent effects of UA were dependent on mitophagy-related genes Parkin and Bnip3.
Conclusions:
- Urolithin A effectively counteracts mitophagy decline and prevents premature senescence in auditory cells.
- UA administration shows promise as a therapeutic strategy for mitigating mitochondrial dysfunction associated with age-related hearing loss.
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