Use of vitamin d and derivative thereof in preparation of product for preventing and / or treating intestinal aging

Abstract

Provided in the present application is use of vitamin D and a derivative thereof in the preparation of a product for preventing and / or treating intestinal aging, which proves that vitamin D has the effects of preventing and / or treating intestinal aging, including reducing the expression of a cyclin-dependent kinase inhibitor 1, improving the permeability of an intestinal tract, increasing the height of small intestinal villi, increasing the depth of a colon crypt, improving the integrity of intestinal tissue structures, improving the expression of a tight junction protein in the intestinal tract, activating some of the T cell-related immune responses, etc.

Description

Application of Vitamin D and its derivatives in the preparation of products for the prevention and / or treatment of intestinal aging

[0001] Technical Field

[0002] This application belongs to the field of food science and technology, specifically relating to the application of vitamin D and its derivatives in the preparation of products for the prevention and / or treatment of intestinal aging. Background Technology

[0003] Aging is a series of degenerative changes that occur in living organisms as they age. Along with the aging process, the functions of multiple tissues and organs in the body undergo degenerative changes. Nervous system decline, cardiovascular aging, intestinal dysfunction, and imbalance of gut microbiota are common manifestations in the elderly.

[0004] Many existing theories suggest that aging begins in the gut. Due to its functions in immunity and nutrient uptake, the gut is considered a vital organ for regulating lifespan. Aging can lead to an imbalance in gut homeostasis, specifically manifested in…

[0005] This condition is characterized by decreased small intestinal digestion and absorption, damage to the intestinal mucosal barrier (e.g., reduced number and length of intestinal villi, reduced number of crypts), weakened intestinal motility, insufficient secretion of digestive enzymes, increased inflammation levels, tissue degeneration, declining regenerative differentiation function of intestinal stem cells, and gut microbiota dysbiosis. Therefore, restoring intestinal homeostasis is of great significance in delaying the aging process and improving the quality of life of the elderly.

[0006] Intestinal aging involves multiple aspects, and there are currently no truly effective drugs for prevention and / or treatment. Moreover, long-term use of drugs can have other side effects. Summary of the Invention

[0007] This application verifies the application of vitamin D in the preparation of products for the prevention and / or treatment of intestinal aging, which can provide a new strategy for the prevention of clinical diseases and has good application prospects in the prevention and / or treatment of intestinal aging.

[0008] According to the first aspect of this application, there is a use of vitamin D in the preparation of products for the prevention and / or treatment of intestinal aging.

[0009] Vitamin D is a micronutrient, primarily obtained through skin synthesis and dietary intake. However, vitamin D2 and vitamin D3 ingested from the skin or diet are biologically inactive and require two chemical reactions in the liver and kidneys to be converted into the biologically functional 1,25-dihydroxyvitamin D3. Many factors influence vitamin D levels in the body, including ultraviolet radiation, dietary supplementation, age, and ethnicity. Currently, the main known functions of vitamin D are regulating calcium and phosphorus absorption and promoting muscle growth and bone development. Increasing research has found that, in addition to its association with bone diseases, vitamin D is also correlated with other tissue and / or systemic diseases, including muscle-related diseases, cardiovascular diseases, autoimmune diseases, and tumors.

[0010] This application is the first to demonstrate that vitamin D can effectively improve intestinal aging. Specifically, through relevant model experiments and data analysis, vitamin D can reduce the expression of cyclin-dependent kinase inhibitor 1 (CDL-1); improve intestinal permeability; increase intestinal villus height; increase colonic crypt depth; improve the integrity of intestinal tissue structure; increase the expression of tight junction proteins in the intestine; and activate some T-cell-related immune functions. In other words, vitamin D can alleviate intestinal aging at the cellular and genetic levels, improve intestinal health, and promote overall health in the gut and other aspects of the body.

[0011] As mentioned above, vitamin D is an essential nutrient for the human body. It has multiple functions, including promoting calcium and phosphorus absorption, promoting new bone formation, promoting skin cell growth, and regulating immune function. It is a nutrient that most people, especially the elderly, need to supplement daily through nutritional supplements or health products. Using vitamin D as a daily nutritional supplement or health product to prevent and / or treat intestinal aging will not bring additional economic burden, psychological burden, or other side effects or adverse effects to the human body. It has a wide range of applications and safety, and the cost is also low, making it worthy of vigorous promotion.

[0012] Preferably, vitamin D and its derivatives include one or more of 1α,25-dihydroxyvitamin D2, 1α-hydroxyvitamin D2, 1α,24-dihydroxyvitamin D2, 1α,24,25-trihydroxyvitamin D2, 1α,25-dihydroxyvitamin D3, 1α-dihydroxyvitamin D3, and 24-hydroxyvitamin D2.

[0013] Preferably, vitamin D and its derivatives are 1α,25-dihydroxyvitamin D3.

[0014] Vitamin D is a group of molecules with identical A, B, C, and D ring structures but different side chains. The structures of the A, B, C, and D rings are derived from the cyclopentanenylphenanthrene ring structure of steroids. Vitamin D exists in various forms, including D2, D3, D4, D5, D6, and D7, depending on the structure of its side chain. However, only the D2 (ergocalciferol) and D3 (cholecalciferol) active forms truly function in nutrition.

[0015] Preferably, the product is a pharmaceutical, health product, or food.

[0016] Preferably, the product is a health supplement, which is at least one of tablets, granules, capsules, powders, oil drops, and solutions.

[0017] Preferably, the health supplement is taken orally.

[0018] Preferably, vitamin D and its derivatives are 1α,25-dihydroxyvitamin D3, and the dosage of 1α,25-dihydroxyvitamin D3 as the active ingredient is 0.1-100 μg / day.

[0019] Preferably, the dosage of 1α,25-dihydroxyvitamin D3 as the active ingredient is 2-15 μg / day.

[0020] Preferably, the prevention and / or treatment of intestinal aging includes at least one of the following:

[0021] (1) Reduce the expression of cycle-dependent kinase inhibitor 1;

[0022] (2) Improves intestinal permeability;

[0023] (3) Increase the height of the small intestinal villi;

[0024] (4) Increase the depth of the colonic crypts;

[0025] (5) Improves the integrity of intestinal tissue structure;

[0026] (6) Increase the expression of tight junction proteins in the gut;

[0027] (7) Activate T cell-related partial immunity.

[0028] Preferably, the activation of T cell-related partial immunity includes at least one of the following:

[0029] (1) Activate gene expression in Th1 and Th2 differentiation pathways;

[0030] (2) Activate the expression of T cell receptor-related pathways.

[0031] The activation of Th1 and Th2 differentiation pathways includes one or more of the following genes: IL-12, STAT1, STAT4, T-Bet, CD3E, CD3G, CD3D, ZAP70, LAT, and IL2R; the activation of T cell receptor-related pathways includes one or more of the following genes: CD8A, CD8B, GADS, and LPC2.

[0032] On the other hand, this application also provides a food, medicine or health product for the prevention and / or treatment of intestinal aging, including vitamin D or its derivatives and a food or medicine-acceptable carrier.

[0033] Compared to existing technologies, this application discloses a novel use of vitamin D, namely, its application in the preparation of drugs, health products, or foods for preventing and / or improving intestinal aging, which has the following advantages:

[0034] (1) This application has discovered new medicinal value of known vitamin D, which has good effects on preventing and / or improving intestinal aging, and has no toxic side effects, thus opening up a new field for the application of vitamin D;

[0035] (2) The series of experimental studies in this application have demonstrated that vitamin D has a preventive and ameliorative effect on gene or cellular structural changes related to intestinal aging, including reducing the expression of cycle-dependent kinase inhibitor 1; improving intestinal permeability; increasing the height of small intestinal villi; increasing the depth of colonic crypts; improving the integrity of intestinal tissue structure; increasing the expression of tight junction proteins in the intestine; and activating T cell-related partial immunity, etc.

[0036] (3) The vitamin D in this application has few toxic side effects, good safety, high acceptance compared to other drugs or health products, and can be taken for a long time, and has good application prospects;

[0037] (4) The vitamin D of this application can be made into various dosage forms, and the dosage is small, convenient to use, and easy to promote. Attached Figure Description

[0038] Figures 1A and 1B show the effects of vitamin D on the gene expression levels of P21 in the small intestine and colon of D-gal model intestinal aging mice, respectively.

[0039] Figure 2 shows the effect of vitamin D on intestinal permeability in D-gal model mice with intestinal aging.

[0040] Figure 3 shows the effect of vitamin D on the height of small intestinal villi in D-gal model mice with intestinal aging.

[0041] Figure 4 shows the effect of vitamin D on the depth of colonic crypts in D-gal model mice with intestinal aging.

[0042] Figure 5 shows the effect of vitamin D on the integrity of intestinal tissue structure in D-gal model aging mice.

[0043] Figures 6A and 6B show the effect of vitamin D on the expression of intestinal tight junction protein in D-gal model intestinal aging mice.

[0044] Figure 7 shows the effect of vitamin D on gene expression in the Th1 and Th2 differentiation pathways in D-gal model intestinal aging mice.

[0045] Figure 8 shows the effect of vitamin D on gene expression of T cell receptor-related pathways in D-gal model intestinal aging mice. Embodiments of the present invention

[0046] To enable those skilled in the art to better understand the present application, the technical solutions in the embodiments of the present application will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present application, and not all embodiments.

[0047] Aging models can be divided into two categories: natural aging models and accelerated aging models. Natural aging models are time-consuming.

[0048] Laborious and costly, accelerated aging models are preferred due to their ease of application, short research time, and minimal experimental intervention.

[0049] High survival rates are a major advantage for aging models. Accelerated aging models come in various types, including in vitro studies induced by basalt treatment and D-galactose, as well as in vivo studies induced by radiation, jet-delayed aging, aging-accelerated mice, Klotho mice, thymectomy, and D-galactose. Among these aging models, D-galactose-induced aging models are the most favored due to their convenience, minimal side effects, and high survival rates throughout the experiment.

[0050] D-galactose is a reducing aldose-hexose that, at high doses, can be converted into aldose and hydrogen peroxide under the catalysis of galactose oxidase, thereby generating reactive oxygen species (ROS). Increased ROS may lead to oxidative stress, inflammation, mitochondrial dysfunction, and apoptosis. In vitro studies have confirmed that D-galactose-induced oxidative stress and inflammatory responses can be generated in different types of senescent cell models.

[0051] 1. Animal Experiment Design

[0052] Eight-week-old male SPF-grade C57BL / 6 mice, weighing 23±1g each, were purchased from Vital River. They were housed at room temperature of 22±2℃ with a 12-hour light-dark cycle, and were allowed to acclimatize for one week after purchase.

[0053] Preparation of experimental reagents:

[0054] aD-galactose: Accurately weigh D-galactose powder (Sigma, A3134), and use it to establish the mouse model at a dose of 500 mg / kg / day, dissolved in distilled water. The intraperitoneal injection volume for each mouse was 100 μL.

[0055] Animal grouping:

[0056] Eight-week-old male SPF-grade C57BL / 6 mice were randomly divided into three groups of eight each: the VD Suff+PBS group (fed a vitamin D-sufficient diet and injected intraperitoneally with PBS daily), the VD Suff+D-Gal group (fed a vitamin D-sufficient diet and injected intraperitoneally with D-galactose daily), and the VD Def+D-Gal group (fed a vitamin D-deficient diet and injected intraperitoneally with D-galactose daily). The normal control group received daily intraperitoneal injections and gavage with saline, while the other groups received daily intraperitoneal injections of D-galactose for four months. During the experiment, all mice had free access to food and water, and their weight was measured weekly.

[0057] Test material collection:

[0058] The day after the last oral administration of the drug to the mice, relevant behavioral experiments were conducted. After the test, the colon, ileum, and duodenum of the mice were taken and their lengths were measured. A portion of the tissue was preserved in tissue fixative, and the other portion was quick-frozen and placed in a -80°C freezer for later use.

[0059] II. Evaluation of Pathological Indicators

[0060] 1) Preliminary preparations

[0061] Material extraction: Using sharp tools to remove intestinal tissue from an animal.

[0062] Fixation: The removed intestinal tissue was immediately immersed in cold PBS, and then the colon was divided into several segments of equal length using dissecting scissors and marked. The portions used for pathological staining were fixed for 24 hours in 4% formaldehyde (PFA) or 10% formalin solution.

[0063] Rinsing: Rinse the intestinal contents with PBS and keep the intestines moist.

[0064] 2) H&E staining of colon tissue

[0065] 2.1 Preparation of intestinal paraffin sections

[0066] Dehydration and paraffin infiltration: The tissue was dehydrated by a gradient of ethanol (70%, 80%, 90%, 100%), then cleared with xylene. The dehydrated tissue block was then immersed in molten paraffin for 30 minutes, and this process was repeated 3 times.

[0067] Tissue embedding: First, pour molten paraffin into the mold, carefully remove the tissue with heated tweezers, and quickly place it into the mold with the cross-section facing upwards. After the paraffin has slightly solidified, cover it with the embedding box base, continue to add wax until the embedding box base is submerged, and allow it to cool to room temperature and solidify.

[0068] Sectioning and spreading: Remove the embedded wax block from the mold and place it on the biological tissue freezing stage. After the wax block cools, fix it on the paraffin microtome. First, adjust the section thickness and trim the section. When complete muscle tissue appears, start continuous sectioning. Each section is 5 μm thick. Use tweezers to remove the section and spread it flat on the water surface of the slide spreader. Use curved tweezers to unfold the folds. The spreading temperature is 42℃.

[0069] Slicing and baking: Once the slices are fully expanded, quickly lift them out with a glass slide, absorb excess water with filter paper, write the numbers on them, and place them on a baking machine. Bake the slices at 42℃ for 2 hours. After baking, place the slices in a 60-70℃ oven overnight to prevent them from falling off.

[0070] At this point, the sections can be dewaxed and rehydrated.

[0071] Reagent time

[0072] xylene 15 min

[0073] Anhydrous ethanol 5 min

[0074] 95% ethanol for 5 minutes

[0075] 80% ethanol for 5 minutes

[0076] 70% ethanol for 5 minutes

[0077] Rinse with tap water for 3 minutes

[0078] 2.2 Pathological H&E staining

[0079] (1) After hydration, the sections were immersed in hematoxylin staining solution for 10 minutes to stain the cell nuclei. Rinse with tap water for 5 minutes;

[0080] (2) Differentiate with 1% hydrochloric acid ethanol for 15 seconds, then rinse with tap water for 3 minutes;

[0081] (3) Then stain in eosin staining solution for 5 minutes to stain the cytoplasm;

[0082] (4) Soak the sections in a series of ethanol solutions (70% ethanol, 80% ethanol, 95% ethanol, and anhydrous ethanol) for 5 minutes each to dehydrate and then section them. Then soak the sections in xylene for 10 minutes to clear them.

[0083] (5) Finally, seal the film with neutral resin.

[0084] 3) Intestinal permeability testing

[0085] Mice were fasted for 6 hours but allowed free access to water, and then administered 100 mg / mL FITC-glucan solution by gavage. The final gavage concentration was 500 mg (FITC-glucan amount) / kg (mouse weight), and the gavage volume was calculated based on the mouse's body weight after 6 hours of fasting. Four hours after gavage, 100-120 μl of blood was collected from the orbital cavity. The blood was placed in a coagulation-promoting tube and incubated in the dark for 2 hours, then centrifuged at 1000×g for 15 min at 4°C to collect serum. Serum from mice that had been gavaged with the same dose of phosphate-buffered saline was used as a negative control. Serum fluorescence values ​​were measured using an ELISA reader at excitation / emission wavelengths of -485 nm / 528 nm, and a standard curve was plotted to quantify the fluorescence signal in each serum sample. Light protection was required throughout the entire process.

[0086] 4) Detection of small intestinal villus height and colonic crypt depth

[0087] After HE staining, the sections are observed under an optical microscope. Measurements are typically taken using an eyepiece equipped with a micrometer or a microscope system connected to image analysis software. For small intestinal villus height, the vertical distance from the villus tip to the villus base (at the junction with the lamina propria) is measured; for colonic crypt depth, the vertical distance from the crypt opening to the crypt base is measured. In each sample, multiple villus and crypts are usually measured (e.g., 10-20), and then the average is calculated to reduce error.

[0088] 5) Detection of expression levels of aging markers, gut tight junction proteins, genes in Th1 and Th2 differentiation pathways, and genes in T cell receptor-related pathways.

[0089] Intestinal tissue was collected, and total RNA was extracted by grinding with Trizol solution. cDNA was obtained by reverse transcription. β-actin was selected as the internal reference gene. Cell cycle-dependent kinase inhibitor 1 (P21) was analyzed in the small and colonic intestines. Tight junction proteins (ZO-1, Occludin, Claudn-1) were also analyzed. In the Th1 and Th2 differentiation pathways, the following proteins were analyzed: IL-12 (interleukin-12), STAT1 (signal transduction and transcription activator 1), STAT4 (signal transduction and transcription activator 4), T-Bet (a novel transcription factor in the T-box gene family), CD3E (T cell receptor), CD3G (T cell receptor), CD3D (T cell receptor), ZAP70 (ζ-chain-associated kinase 70), LAT (T cell activation connective protein), and IL2R (interleukin-2 receptor). In the T cell receptor-related pathway, CD8A (type I transmembrane glycoprotein on the surface of T lymphocytes), CD8B (type I transmembrane glycoprotein on the surface of lymphocytes), GADS (downstream adaptor protein), and LPC2 (Lipocalin-2) were also analyzed. Gene expression status.

[0090] Example 1: Effect of vitamin D on gene expression levels of small intestinal P21 and colonic P21 in D-gal model intestinal aging mice.

[0091] Cycle-dependent kinase inhibitor 1 (P21) is a negative regulator of the cell cycle. P21 inhibits the cylin-CDK complex, causing cell cycle arrest in the G1 phase. It is highly expressed in senescent cells. As shown in Figure 1, compared with the control group, vitamin D intervention in D-gal modeled intestinal senescent mice significantly reduced the cell senescence marker gene P21 in both the small intestine and colon.

[0092]

[0093] Example 2: Vitamin D improves intestinal permeability in D-gal model mice with intestinal aging

[0094] Intestinal permeability can be evaluated by detecting the entry of fluorescently labeled macromolecular compounds into the bloodstream after intestinal absorption. As shown in Figure 2, compared with the control group, the intestinal permeability of the model group mice was significantly increased, indicating that...

[0095] Prolonged and continuous intake of D-galactose can alter intestinal permeability. Compared with the model group, vitamin D intervention significantly reduced intestinal permeability in mice, indicating that vitamin D supplementation can alleviate the changes in intestinal barrier permeability caused by D-galactose.

[0096] Example 3: Effects of Vitamin D on Colonic Tissue Morphology in D-gal Model Intestinal Aging Mice

[0097] The height of intestinal villi has a significant impact on intestinal function, and the height and morphology of the villi directly affect their ability to absorb nutrients. Longer villi have a larger surface area, thus enabling the absorption of more nutrients. As shown in Figures 3 and 5, the H&E staining results of the intestines of mice in each group reveal that the intestinal villi height of the D-gal aging group was significantly lower than that of the normal control group, a clear characteristic of intestinal aging. The intestinal villi height of the colon in the vitamin D intervention group was significantly longer than that in the D-gal aging group.

[0098] As shown in Figures 4 and 5, the H&E staining results of the intestines of mice in each group reveal that, compared with the normal control group, the D-gal aging group mice exhibited significantly reduced colonic crypt depth and sparser, looser arrangement, a clear characteristic of intestinal aging that leads to decreased intestinal motility. The vitamin D intervention group mice showed significantly longer colonic crypt depth and a more compact and orderly arrangement compared to the D-gal aging group mice.

[0099] As shown in Figure 5, the colon tissue structure of the control group was normal, the intestinal glands in the lamina propria were arranged neatly and tightly, the gland structure was clear and complete, and there was no deformation or atrophy. The colon gland structure of the model group was changed, the intestinal glands were loosely arranged, the glands were deformed and atrophied, and the gaps were widened. The glands in the colon of mice in the vitamin D intervention group were more neatly arranged, and the damage to the intestinal gland structure was reduced to a certain extent.

[0100] Example 4: Effect of Vitamin D on Intestinal Tight Junction Protein Expression in D-gal Model Intestinal Aging Mice

[0101] Tight junction proteins are composed of cytoplasmic attachment proteins, transmembrane proteins, and cytoskeletal proteins. Tight junctions are primarily located in the junctional complexes between epithelial and endothelial cells, bringing adjacent cell membranes together to form a physical barrier structure surrounding the cell. Transmembrane proteins include three types of intact membrane proteins: junction adhesion molecules (JAMs), ocludin, and closure proteins (Claudin). Currently, ocludin and Claudin are considered to play major roles among transmembrane proteins, with Claudin being particularly important as it is the main protein responsible for the formation of tight junctions.

[0102] The ZO-1 protein can interact with other tight junction proteins (such as claudin and occludin) to form a complex that mediates intercellular tight junctions and signal transduction. Its functions involve multiple aspects, including cell polarity differentiation, cell adhesion, and cell movement.

[0103] Intestinal tight junction proteins are important molecules that form tight junctions between intestinal cells, playing a crucial role in maintaining the integrity and permeability of the intestinal mucosal barrier. When the expression of intestinal tight junction proteins is abnormal, the integrity of the intestinal mucosal barrier is impaired, and permeability increases.

[0104] As shown in Figures 6A and 6B, the expression levels of intestinal tight junction protein genes (ZO-1, Occludin, Claudn-1) were significantly downregulated in the D-gal aging group, while the degree of reduction in the expression levels of each tight junction protein was less after vitamin D intervention.

[0105] Example 5: Effects of Vitamin D on Immunity in D-gal Model Intestinal Aging Mice

[0106] The D-galactose-induced aging model not only successfully simulated the aging process but also produced relatively ideal pathological features. These changes included oxidative stress, inflammation, apoptosis, mitochondrial dysfunction, and upregulation of P53 and P21 gene expression, which are consistent with natural aging. This experiment used D-galactose-induced aging mice as the research subjects to study the effect of vitamin D on intestinal inflammation.

[0107] As shown in Figures 7 and 8, compared with the normal control group, vitamin D administration increased gene expression in the Th1 and Th2 differentiation pathways, as well as in the T-cell receptor-related pathway. Enhanced systemic inflammation in mice is associated with accelerated aging and increased risk of death, while anti-inflammatory intervention can rescue mice from premature aging.

[0108] In summary, it can be seen that the use of vitamin D has an improving effect on the expression of intestinal tight junction protein genes and immune-related genes, and also inhibits the expression of intestinal aging marker genes, which helps to delay intestinal structural aging.

[0109] The above embodiments are only used to illustrate the technical solutions of this application and are not intended to limit the scope of protection of this application. Although this application has been described in detail with reference to the above embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of this application, but such modifications or substitutions are all within the scope of protection of this application.

Claims

1. Application of vitamin D and its derivatives in the preparation of products for the prevention and / or treatment of intestinal aging.

2. The application as described in claim 1, wherein vitamin D and its derivatives include one or more of 1α,25-dihydroxyvitamin D2, 1α-hydroxyvitamin D2, 1α,24-dihydroxyvitamin D2, 1α,24,25-trihydroxyvitamin D2, 1α,25-dihydroxyvitamin D3, 1α-dihydroxyvitamin D3, and 24-hydroxyvitamin D2.

3. The application as described in claim 2, wherein vitamin D and its derivatives are 1α,25-dihydroxyvitamin D3.

4. The application as described in claim 1, wherein the product is a pharmaceutical, health product, or food.

5. The application as described in claim 4, wherein the product is a health supplement, and the health supplement is at least one of tablets, granules, capsules, powders, oil drops, and solutions.

6. The application as described in claim 5, wherein the health product is taken orally.

7. The application according to claim 5, wherein, Vitamin D and its derivatives are 1α,25-dihydroxyvitamin D3, and the dosage of 1α,25-dihydroxyvitamin D3 as the active ingredient is 0.1-100 μg / / d. Preferably, the dosage of 1α,25-dihydroxyvitamin D3 as the active ingredient is 2-15 μg / d.

8. The application according to claim 1, wherein, The prevention and / or treatment of intestinal aging includes at least one of the following: (1) Reduce the expression of cycle-dependent kinase inhibitor 1; (2) Improves intestinal permeability; (3) Increase the height of the small intestinal villi; (4) Increase the depth of the colonic crypts; (5) Improves the integrity of intestinal tissue structure; (6) Increase the expression of tight junction proteins in the gut; (7) Activate T cell-related partial immunity.

9. The application according to claim 1, wherein, The T-cell-related partial immunity includes at least one of the following: (1) Activate gene expression in Th1 and Th2 differentiation pathways; (2) Activate the expression of T cell receptor-related pathways.

10. A food, medicine, or health product for the prevention and / or treatment of intestinal aging, including vitamin D or a derivative thereof and a food or medicine-acceptable carrier.

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