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Crocetin delays brain and body aging by increasing cellular energy levels and enhances the median life span in aged C57BL/6J mice
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  • Sushil Choudhary,
  • Vishnu Kumar,
  • Kuhu Sharma,
  • Abhishek Gour,
  • Ashish Sahrawat,
  • Anshika Jotshi,
  • Diksha Manhas,
  • Utpal Nandi,
  • Sandip Bharate,
  • Zabeer Ahmed,
  • Ajay Kumar
Sushil Choudhary
CSIR Indian Institute of Integrative Medicine
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Vishnu Kumar
Justus Liebig University Giessen Institute of Anatomy and Cell Biology
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Kuhu Sharma
Indian Institute of Integrative Medicine CSIR
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Abhishek Gour
Indian Institute of Integrative Medicine CSIR
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Ashish Sahrawat
Indian Institute of Science
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Anshika Jotshi
Indian Institute of Integrative Medicine CSIR
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Diksha Manhas
Indian Institute of Integrative Medicine CSIR
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Utpal Nandi
Indian Institute of Integrative Medicine CSIR
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Sandip Bharate
Indian Institute of Chemical Technology
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Zabeer Ahmed
Council of Scientific & Industrial Research Indian Institute of Integrative Medicine
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Ajay Kumar
Indian Institute of Integrative Medicine CSIR

Corresponding Author:[email protected]

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Abstract

Abstract Background and Purpose Aging is usually accompanied by mitochondrial dysfunction, reduced energy levels, and cell death in the brain and other tissues. Mitochondria play a crucial role in maintaining cellular energy through oxidative phosphorylation (OXPHOS). However, OXPHOS is impaired as mitochondrial oxygen supply decreases with age. We explored whether pharmacologically increased oxygen diffusion by crocetin can restore OXPHOS and help delay aging of brain and other vital organs. Experimental Approach Stress-free chronic treatment of aged C57BL/6J mice with crocetin followed by an analysis of behavior, hippocampi whole transcriptome, and key energy metabolites by LCMS was performed. Key Results The aged mice treated with crocetin for four months displayed significantly improved memory behavior, neuromuscular coordination, and ATP and NAD+ levels in the brain and other vital organs, leading to an increased median life span. The transcriptomic analysis of hippocampi from crocetin-treated mice revealed that enhanced brain energy level was caused by the upregulation of genes linked to OXPHOS, and their expression was close to the expression in young mice. The chronic treatment of aged astrocytes also showed improved mitochondrial membrane potential and energy state of the cells. Conclusion and Implications Our data suggest that restoring the OXPHOS and the normal energy state of the cell can delay aging and enhance longevity. Therefore, molecules like crocetin should further be explored to treat age-related diseases.
28 Sep 2023Submitted to British Journal of Pharmacology
04 Oct 2023Submission Checks Completed
04 Oct 2023Assigned to Editor
04 Oct 2023Review(s) Completed, Editorial Evaluation Pending
23 Oct 2023Reviewer(s) Assigned