The role of curcumin supplements in delaying aging
Aging, as a natural and irreversible physiological process, is closely related to various geriatric diseases. Curcumin, as the main active component in turmeric, has attracted much attention in the field of aging research in recent years. This article comprehensively reviews the chemical properties, metabolic process and biological activities of curcumin, elaborates in detail its mechanism of action in delaying aging and preventing and treating related diseases, and comprehensively analyzes the relevant clinical research results, aiming to provide a reference basis for the in-depth research and application of curcumin in the field of aging intervention.
Key words: Curcumin Aging Antioxidant Anti-inflammatory Cellular signaling pathways.
1. Introduction
The acceleration of the global aging process has made the prevention and treatment of aging-related diseases an important research direction in the current biomedical field. Aging can lead to the continuous decline of the body's functions and significantly increase the risk of various diseases such as cardiovascular diseases, neurodegenerative diseases and cancer. Therefore, exploring safe and effective anti-aging intervention measures has become the focus of attention for many scientific researchers. Curcumin is a natural compound extracted from the plant turmeric. With its diverse biological activities and potential health benefits, it has demonstrated unique value in the research of anti-aging.
2. Biological Mechanisms of Aging
The occurrence and development of aging is an extremely complex process, which is jointly influenced by multiple factors such as genetics, environment and lifestyle. From the molecular and cellular levels, in-depth analysis reveals that aging has multiple typical characteristics, covering abnormal DNA damage and repair, telomere shortening, epigenetic changes, imbalance of protein homeostasis, dysregulation of nutritional perception, mitochondrial dysfunction, cellular aging, stem cell exhaustion, and abnormal intercellular communication, among others. These characteristics interweave with each other, jointly driving the body towards aging, which in turn leads to the decline of cell functions, damage to tissues and organs, and a significant increase in the body's susceptibility to diseases. Oxidative stress plays a key role in the aging process. It mainly stems from the imbalance between the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the body and the antioxidant defense system. With the increase of age, the antioxidant capacity of the human body gradually declines, and ROS and RNS accumulate continuously in the body. These excessive free radicals can cause oxidative damage to lipids, proteins and DNA within cells, thereby triggering cellular dysfunction and becoming an important inducement for the occurrence and development of aging-related diseases. Meanwhile, the inflammatory response gradually intensifies during the aging process. The chronic inflammatory state is closely related to various geriatric diseases, further accelerating the pace of aging.
3. Chemical Properties and Metabolism of Curcumin
Curcumin is an orange-yellow pigment extracted from the rhizome of turmeric, with the chemical name of diferulic acmethane. Its molecular structure is symmetrical. At present, common extraction methods include solvent extraction and column chromatography, etc. These methods can effectively separate curcumin from turmeric. The metabolism of curcumin in the human body mainly occurs in the liver, intestines and intestinal flora. After oral administration, it is metabolized into various different products in the gastrointestinal tract, such as glucuronic acid conjugates, sulfate conjugates, and reduction metabolites (such as hexahydrocurcumin), etc. Some metabolites not only have higher stability than curcumin, but also possess various biological activities such as antioxidation, anti-inflammation and anti-tumor. All these lay the foundation for curcumin to exert multi-pharmacological effects.
4. Biological Activity and Anti-Aging Mechanism of Curcumin
4.1 Anti-oxidative stress
Curcumin has outstanding antioxidant activity and can efficiently eliminate ROS and RNS in the body, reducing aging damage. Inside the cell, it can directly capture and neutralize excessive free radicals, inhibit lipid peroxidation reactions, reduce the generation of lipid peroxidation products such as malondialdehyde (MDA), and lower the level of protein carbonylation, thereby protecting the normal structure and function of proteins. Meanwhile, curcumin can also inhibit DNA oxidative damage, reduce the formation of oxidative damage markers such as 8-hydroxydeoxyguanosine (8-OHdG), and maintain the stability of the genome. Curcumin can also regulate the antioxidant enzyme system, thereby enhancing the body's antioxidant defense capacity. It can up-regulate the expression levels of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), enhance their activities, promote the catabolism of ROS, and maintain the balance of REDOX states within cells. During the aging process, the body's antioxidant capacity declines. However, the antioxidant effect of curcumin can effectively alleviate the damage caused by oxidative stress to cells and tissues, protect the normal functions of cells, and thereby delay the aging process.
4.2 Anti-inflammatory effect
Optimizing the aging microenvironment Inflammation is an important feature of aging. A chronic inflammatory state will accelerate cellular aging and tissue degeneration. Curcumin can inhibit the activation of inflammatory signaling pathways, especially showing a more significant inhibitory effect on the NF-κB pathway. NF-κB is a key regulatory factor of the inflammatory response. During the aging process, various stimulating factors can activate NF-κB, thereby leading to the massive release of inflammatory cytokines. Curcumin reduces the intensity of the inflammatory response by inhibiting the activation of NF-κB and decreasing the production of inflammatory cytokines such as interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF-α). In addition, curcumin can also regulate the function of inflammatory cells, inhibit the chemotaxis and infiltration of inflammatory cells, and reduce the damage of inflammation to tissues. In the occurrence and development of chronic diseases related to aging, such as cardiovascular diseases and neurodegenerative diseases, inflammatory responses play an important promoting role. The anti-inflammatory properties of curcumin help improve the pathological conditions of these diseases, reduce the damage of inflammation to the body, create a microenvironment that is more conducive to cell survival and function maintenance, and thereby delay the aging process.
4.3 Adjust telomere length
Telomeres, which maintain cell vitality, are repetitive DNA sequences at the ends of chromosomes, and their length gradually shortens as cells divide and age. When telomeres shorten to a certain extent, cells will enter a state of senescence or apoptosis. Curcumin can promote telomere elongation by enhancing the activity of telomerase. Telomerase is an enzyme that can extend the length of telomeres. In normal cells, its activity is relatively low. However, curcumin can activate telomerase, enabling it to maintain the length of telomeres and the stability of chromosomes. It was found in in vitro cell experiments and animal studies that after curcumin treatment, the telomere length of cells was effectively maintained, the proliferation ability and viability of cells were enhanced, and the expression of age-related β -galactosidase was reduced. This fully demonstrates that curcumin can delay cellular senescence and maintain the normal functions of cells by regulating telomere length, which is of great significance for tissue repair and regeneration.
4.4 Regulate aging-related proteins and signaling pathways and reshape cell fate
4.4.1 Regulate the mTOR signaling pathway
The mTOR signaling pathway plays a key role in the regulation of cell growth, metabolism and senescence. During the aging process, the mTOR signaling pathway is overly activated, which leads to excessive cell growth, metabolic disorders, and impaired autophagy function, thereby accelerating cell aging. Curcumin can inhibit the activity of mTOR and block the excessive activation of the mTOR signaling pathway. In various cell models, after treatment with curcumin, the phosphorylation levels of the downstream target proteins S6K1 and 4E-BP1 of mTOR decreased, the growth and proliferation of cells were moderately regulated, and the autophagy function was also enhanced. Autophagy is an important self-cleaning mechanism within cells, capable of eliminating harmful substances such as damaged organelles and protein aggregates. Curcumin helps cells maintain the stability of their internal environment and reduce the accumulation of harmful substances by activating autophagy, thereby delaying cellular aging.
4.4.2 Activate the AMPK signaling pathway
AMPK is a key regulatory factor of cellular energy metabolism and plays an important role in maintaining cellular energy balance and metabolic homeostasis. With the increase of age, the activity of AMPK gradually decreases, which can lead to disorders in cellular energy metabolism and weakened resistance to various stresses. Curcumin can act as an agonist of AMPK, enhancing the phosphorylation level of AMPK and activating the AMPK signaling pathway. The activated AMPK can regulate multiple metabolic pathways within cells, promote the oxidation of fatty acids, the uptake and utilization of glucose, and inhibit the synthesis of fatty acids and cholesterol, thereby maintaining the energy balance of cells. In addition, AMPK can enhance the stress resistance of cells, activate the antioxidant defense system, and inhibit inflammatory responses. All these effects help to delay cell aging and maintain the healthy state of cells.
4.4.3 Regulate the sirtuins protein family
sirtuins are a type of NAD-dependent deacetylases that play a significant role in DNA repair, maintaining genomic stability, regulating cellular metabolism, and regulating aging. Curcumin can activate members such as Sirt1 in the sirtuins family and promote the deacetylation modification of proteins. During the process of cellular senescence, the acetylation status of many key proteins changes, thereby affecting the functions of the cells. After Sirt1 is activated, it can deacetylate some proteins related to aging, such as p53, FOXO, etc. Deacetylated p53 and FOXO can exert more effective cell protection and antioxidant effects, promoting cell survival and repair. Meanwhile, Sirt1 can also regulate the function of mitochondria, enhance their biosynthesis and energy metabolism, reduce the production of ROS, and further delay cellular aging.
5. The Protective Effect of Curcumin on Brain Aging
Brain aging is often accompanied by pathological changes such as oxidative stress, mitochondrial dysfunction and cell death, and these changes are prone to cause neurodegenerative diseases. Curcumin has a good neuroprotective effect. It can cross the blood-brain barrier and regulate various biological processes within the brain. In the nervous system, curcumin can inhibit the excessive activation of microglia and reduce the release of inflammatory factors, thereby regulating the inflammatory response. Microglia are immune cells in the brain. When aging and neurodegenerative diseases occur, microglia are overly activated, releasing a large number of inflammatory factors that cause damage to nerve cells. Curcumin reduces the production of inflammatory factors and alleviates the damage of neuroinflammation to nerve cells by inhibiting inflammatory signaling pathways such as NF-κB. Meanwhile, curcumin can promote the transformation of microglia to the M2 phenotype with neuroprotective effects, reduce the level of oxidative stress, and alleviate nerve cell damage. Studies have shown that curcumin has potential therapeutic effects on neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, and can improve cognitive function and delay the progression of the disease. Taking the Alzheimer's disease model as an example, curcumin can reduce the formation of amyloid plaques, inhibit the excessive phosphorylation of tau protein, protect neurons from damage, and thereby improve cognitive function.
6. Clinical Research evidence of Curcumin
Multiple clinical studies have evaluated the efficacy of curcumin in the treatment of various diseases. In the treatment of psoriasis, curcumin, as an adjuvant therapeutic method, can significantly reduce the level of IL-22 in serum, alleviate skin inflammation, and inhibit the abnormal proliferation of keratinocytes, thereby improving the symptoms of psoriasis. For patients with vitiligo, the combined treatment of narrow-band ultraviolet B (NB-UVB) and curcumin drugs can promote skin pigmentation and improve the therapeutic effect. In the treatment of arthritis, curcumin can inhibit inflammation-related proteins and signaling pathways, alleviate the symptoms of joint inflammation, and delay the progression of the disease. In addition, curcumin has also demonstrated a positive role in the prevention and treatment of cardiovascular diseases. It can improve vascular endothelial function, lower blood lipid levels, alleviate oxidative stress and inflammatory responses, thereby reducing the risk of cardiovascular diseases. However, in the clinical research of Alzheimer's disease, although curcumin has shown certain therapeutic effects in animal models, due to its low bioavailability and problems in clinical trial design, it has not yet achieved ideal clinical therapeutic effects.
7. Safety and Side Effects of Curcumin
Overall, curcumin has relatively good safety. In clinical studies, high doses of curcumin may cause some mild adverse reactions, such as diarrhea, headache, rash and yellow stools, etc. When used at low doses, some patients may experience nausea, elevated levels of serum alkaline phosphatase and lactate dehydrogenase, etc. However, research shows that the human body can usually safely tolerate it within a certain period of time (for example, consuming up to 8000mg of turmeric supplement daily for 8 months, or up to 8000mg of curcumin daily for 3 months). When curcumin is used in combination with bioavailability enhancers such as piperine, although it can increase its bioavailability, it may have a certain impact on safety. Therefore, careful assessment is needed when using it.
8. Conclusions and Prospects
Curcumin, as a natural compound, shows multiple potentials in delaying aging and preventing and treating related diseases. It plays a regulatory role in multiple key links of the aging process through various mechanisms such as antioxidation, anti-inflammation, and regulation of cellular signaling pathways. Although the bioavailability issue of curcumin currently limits its full therapeutic effect in clinical applications, with the development of new dosage forms (such as nanoparticles, liposomes, etc.), it is expected to increase its bioavailability and enhance the therapeutic effect. Future research requires further in-depth exploration of the mechanism of action of curcumin to clarify its optimal dosage and course of treatment in different populations and disease states. Meanwhile, research on the combined use of curcumin with other drugs or nutrients should be strengthened to explore synergistic treatment plans, so as to give full play to the value of curcumin in aging intervention and disease prevention and treatment, and provide new strategies and methods for improving the health status of the elderly.
Izadi M, Sadri N, Abdi A,et al, Longevity and anti-aging ects of curcumin supplementation. GeroScience 2024; Prepared his 33-2950.
https://doi.org/10.1007/s11357-024-01092-5
