Sirtuin Signaling in Oocyte Quality and Aging
Summary
Sirtuin proteins are emerging as central regulators of oocyte competence and ovarian ageing, acting through their NAD⁺-dependent deacetylase activities to coordinate genome stability, mitochondrial function and redox homeostasis. In young oocytes, SIRT1 ensures proper chromatin modifications and DNA repair, while mitochondrial sirtuins such as SIRT3 and SIRT4 maintain ATP production, control reactive oxygen species levels and support meiotic spindle assembly. With advancing maternal age, depleted NAD⁺ pools and impaired sirtuin signalling contribute to mitochondrial dysfunction, oxidative damage, spindle anomalies and reduced ovarian reserve. Experimental restoration of NAD⁺ levels or direct activation of sirtuins has been shown to rejuvenate oocyte mitochondrial bioenergetics, stabilise spindle integrity and diminish oxidative insults, highlighting sirtuin pathways as promising targets to mitigate age-related fertility decline and enhance outcomes in assisted reproductive technologies.
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Sirtuin Signaling in Oocyte Quality and Aging publication trend
The graph below shows the total number of articles in sirtuin signaling in oocyte quality and aging across all publications each year (not limited to Nature Index journals).
Technical terms
Sirtuins: A family of nicotinamide adenine dinucleotide (NAD⁺)-dependent enzymes that remove acetyl groups from proteins, influencing chromatin structure, metabolism and stress responses.
NAD⁺ (nicotinamide adenine dinucleotide): A coenzyme essential for energy metabolism and the obligatory substrate for sirtuin-catalysed deacetylation reactions.
Deacetylase: An enzyme that removes acetyl groups from lysine residues on histones and other proteins, modulating their activity and interactions.
Autophagy: A lysosome-mediated process that degrades and recycles damaged organelles and proteins to maintain cellular homeostasis.
Mitophagy: The selective form of autophagy targeting dysfunctional mitochondria for removal, essential for mitochondrial quality control.
Reactive oxygen species (ROS): Highly reactive oxygen-containing molecules that, at elevated levels, cause oxidative damage to lipids, proteins and DNA.
Granulosa cells: Somatic cells surrounding the oocyte within the follicle that provide metabolic substrates, signalling factors and structural support critical for oocyte growth and maturation.
References
- Nicotinamide mononucleotide supplementation rescues mitochondrial and energy metabolism functions and ameliorates inflammatory states in the ovaries of aging mice. MedComm (2024).
- NAD+ Metabolism and Mitochondrial Activity in the Aged Oocyte: Focus on the Effects of NAMPT Stimulation. Aging and Disease (2024).
- Sirtuin 3 regulation: a target to alleviate β-hydroxybutyric acid-induced mitochondrial dysfunction in bovine granulosa cells. Journal of Animal Science and Biotechnology (2023).
- SIRT4 is essential for metabolic control and meiotic structure during mouse oocyte maturation. Aging Cell (2018).
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