This article focuses on crocetin, elaborating on its potential as a natural compound in delaying aging and improving neurodegenerative diseases. Studies have shown that crocetin can improve mitochondrial function in aged mice by increasing oxygen diffusion, enhance their memory, coordination, and energy levels, and extend the median survival time. Meanwhile, it reveals the molecular mechanisms of its action, such as regulating the expression of related genes, providing a basis for its application in anti-aging and the treatment of related diseases.
As the global population ages, the issue of aging and age-related diseases has attracted increasing attention. With the passage of time, the function of various organs in the human body gradually declines, and this process is closely linked to the rising incidence of neurodegenerative diseases. Among the many factors contributing to aging and neurodegenerative diseases, mitochondrial dysfunction has long been regarded as a key player. As people grow older, a series of physiological changes occur, such as decreased lung function, anemia, and microcirculatory disorders. These changes lead to insufficient oxygen supply to tissues, triggering chronic hypoxia. Chronic hypoxia, in turn, exacerbates mitochondrial dysfunction, forming a vicious cycle that promotes the progression of neurodegenerative diseases.
Crocetin, a natural compound, has long been noticed for its various biological activities, and in recent years, it has shown great potential in improving mitochondrial function. Recently, the research team led by Ajay Kumar from the Institute of Integrative Medicine in India published a research paper entitled "Crocetin Delays Brain and Body Aging by Increasing Cellular Energy Levels in Aged C57BL/6J Mice" in ACS Pharmacology & Translational Science. This groundbreaking study found that crocetin can improve mitochondrial function in aged mice by increasing oxygen diffusion, thereby enhancing their memory, coordination, and energy levels, and even extending their lifespan.
Improvements in Behavioral and Physical Functions of Aged Mice after Crocetin Treatment
The research results clearly demonstrated that crocetin, by promoting oxygen diffusion, effectively ameliorates mitochondrial function in aged mice. This improvement is not only reflected at the cellular level but also in the overall behavior and physical condition of the mice. After a four-month crocetin treatment on aged mice, significant improvements were observed in their memory behavior and motor ability. In spatial memory tests, the treatment group performed exceptionally well. They took less time to find food, spent more time in the bait arm, and made fewer mistakes by entering non-bait arms. These results strongly indicate that crocetin has a positive impact on enhancing memory function in aged mice.
Figure: Elderly mice showed significant improvements in brain function after four months of long-term treatment with crocin.
In addition to memory improvement, the crocetin-treated group also showed more frequent activities in the open field test, with increased movement distance and speed, which fully reflects the improvement in their motor ability and energy levels. Pharmacokinetic studies further revealed that crocetin has a low concentration in the brain and no accumulation phenomenon, suggesting that it may have good safety in long-term use, which is an important prerequisite for its potential clinical application. Overall, crocetin has effectively improved the cognitive and motor functions of aged mice, laying a solid foundation for further research.
Molecular Mechanisms Underlying Crocetin's Effects on Memory and Brain Function
To explore the molecular mechanism underlying the effect of crocetin on the memory behavior of mice, the researchers conducted whole-transcriptome sequencing on the mouse hippocampus. The results showed that crocetin treatment caused significant changes in gene expression. Specifically, it upregulated genes such as BDNF, GBBR2, GAD2, and DROSHA, which are closely related to the improvement of brain function and behavior. At the same time, it downregulated genes including HCK, AMIGO3, TOP1MT, and LCP1. More importantly, genes related to the mitochondrial electron transport chain (ETC) were significantly upregulated, which further supports the molecular mechanism by which crocetin improves brain function, that is, by regulating the expression of related genes to enhance mitochondrial function and then promote brain function.
Further analysis of the mitochondrial genome showed that crocetin did not change the single nucleotide polymorphisms (SNPs) or insertions/deletions (InDels) in the mitochondrial genome of aged mice. This indicates that its anti-aging effect does not depend on changes in genome stability, which is a new insight into the mechanism of crocetin's action, distinguishing it from some other anti-aging substances that act by maintaining genome stability.
Impacts of Crocetin on Cellular Oxygen Supply, Organ Function, and Lifespan
The study also found that under hypoxic conditions, crocetin can reduce the expression of HIF1α in astrocytes. HIF1α is a key factor in the body's response to hypoxia, and the reduction in its expression suggests that crocetin helps to improve the oxygen supply to cells, thereby reducing oxidative stress. Oxidative stress is an important factor in aging and neurodegenerative diseases, so the reduction of oxidative stress by crocetin is another important aspect of its beneficial effects. After treating aged astrocytes with crocetin, the mitochondrial membrane potential and the expression of inner mitochondrial membrane proteins ND5 and ND6 increased, and the levels of NAD+ and ATP also increased. These results collectively indicate that crocetin can enhance mitochondrial function and restore the cellular energy metabolism state, which is crucial for maintaining cell vitality and normal physiological functions.
In addition to its effects on the brain, long-term treatment with crocetin also had positive impacts on other important organs of the mice. It not only increased the levels of ATP and NAD+ in the heart, kidneys, lungs, and liver but also significantly improved the metabolic rate of these organs. Although no significant biochemical and hematological changes were found except for platelet counts, crocetin treatment improved the neuromuscular coordination and grip strength of the mice, which are important indicators of physical function. Most notably, crocetin extended the median survival time of the mice from 744 days to 876 days, an increase of 17.7%. This significant extension of lifespan further highlights the potential of crocetin in anti-aging.
In summary, crocetin restores mitochondrial function by increasing oxygen diffusion, thereby significantly improving the memory, coordination, and energy levels of aged mice and extending their lifespan. Genetic analysis shows that crocetin enhances brain energy by upregulating genes related to oxidative phosphorylation (OXPHOS), and long-term use does not cause oxidative stress. These results provide strong evidence for the potential application of crocetin in delaying aging and treating related diseases. With the deepening of research, it is expected that crocetin will play an important role in improving human health and quality of life in the future.