Selenoproteins and the senescence-associated epitranscriptome.

Area of Science:

• Biochemistry and Molecular Biology
• Cellular Senescence
• Epigenetics and Epitranscriptomics

Background:

• Selenium is an essential trace element with antioxidant, anticancer, and immune-boosting properties.
• Selenoproteins, incorporating the 21st amino acid selenocysteine, are key for redox homeostasis and antioxidant defense.
• Selenocysteine incorporation involves a unique UGA stop codon recoding mechanism.

Purpose of the Study:

• To investigate the role of upstream events regulating selenoprotein synthesis in senescence-associated pathologies.
• To explore the connection between epitranscriptomic marks, selenocysteine utilization, and the cellular senescence program.

Main Methods:

• Review of existing literature on selenium, selenoproteins, aging, and senescence.
• Focus on the function of alkylation repair homolog 8 (ALKBH8) in selenoprotein production.
• Analysis of the impact of ALKBH8 deficiency on reactive oxygen species (ROS) detoxification and oxidative stress.

Main Results:

• ALKBH8 is critical for selenoprotein synthesis; its deficiency reduces selenoprotein levels.
• Decreased selenoproteins lead to impaired ROS detoxification and increased oxidative stress.
• Increased oxidative stress is a major driver of cellular senescence.

Conclusions:

• Epitranscriptomic regulation of selenocysteine incorporation may play a significant role in cellular senescence.
• Dysregulation of selenoprotein synthesis due to impaired epitranscriptomic marks could contribute to senescence-associated pathologies.
• Further research into epitranscriptomic marks governing selenoprotein synthesis is warranted to understand aging and related diseases.