An oral anti-aging composition based on telomere protection

Abstract

This invention relates to an oral anti-aging composition based on telomere protection, belonging to the fields of biomedicine and functional food technology. The composition comprises 15-25 parts of cycloastragalol, 4-8 parts of astaxanthin, 200-400 parts of epigallocatechin gallate, 200-400 parts of nicotinamide ribose, 40-60 parts of mixed nucleotides, and 1500-2500 IU of vitamin D3. In this invention, cycloastragalol activates telomerase, actively elongating telomeres; astaxanthin and EGCG stabilize the G-quadruplex structure of telomeres and provide targeted antioxidant protection; and nicotinamide ribose enhances NAD+. + This invention enhances the telomere-specific DNA damage repair capacity. It systematically intervenes in telomere shortening from multiple targets, and can be used to prepare oral anti-aging products that delay cellular aging.

Description

Technical Field

[0001] This invention relates to the fields of biomedicine and functional food technology, and more particularly to an oral anti-aging composition based on telomere protection. Background Technology

[0002] Telomeres are non-coding repetitive sequences and related protein complexes at the ends of eukaryotic chromosomes. Their function is to protect chromosome ends from being recognized as DNA breakpoints, preventing chromosome end fusion or degradation. During each cell division, telomere DNA loses base pairs due to end replication issues. When telomere length shortens to a critical threshold, the cell initiates a DNA damage response, triggering replicative senescence or apoptosis. Therefore, telomere length is widely recognized as the "molecular clock" of cellular aging, and progressive telomere shortening is one of the important drivers of aging and tissue dysfunction. Maintaining or extending telomere length has become a key strategy for intervening in cellular aging and delaying age-related functional impairment.

[0003] Based on the above understanding, researchers are dedicated to developing oral compositions that can maintain or prolong telomere length. Among existing technologies, telomerase activation is considered the most direct intervention pathway. Telomerase is a ribonucleoprotein complex that synthesizes telomeric DNA repetitive sequences using its built-in RNA template, thereby compensating for telomere wear during cell division. Cycloastragenol is a triterpenoid saponin compound extracted from the traditional Chinese medicine Astragalus membranaceus, and is a transcriptional activator of the telomerase catalytic subunit (TERT). Studies have shown that cycloastragenol enhances telomerase activity by upregulating TERT gene expression, thereby delaying telomere shortening. Based on this mechanism, cycloastragenol is widely considered to have anti-aging potential and has been applied in various oral anti-aging compositions.

[0004] However, relying solely on cycloastragalool to activate telomerase has several shortcomings: first, telomere DNA suffers from oxidative damage and G-quadruplex structural instability; second, telomerase elongation efficiency is low when telomere DNA is oxidatively damaged or structurally unstable; and third, senescent cells are often accompanied by NAD+. + As telomere levels decrease, the repair efficiency of telomere damage also decreases. Summary of the Invention

[0005] To address the aforementioned problems in existing technologies, this invention provides an oral anti-aging composition based on telomere protection. The composition comprises cycloastragalool, astaxanthin, epigallocatechin gallate, nicotinamide ribose, mixed nucleotides, and vitamin D3. Cycloastragalool activates telomerase, astaxanthin and EGCG protect telomere structure, and nicotinamide ribose enhances telomere DNA damage repair, achieving a multi-dimensional synergistic effect of "activation-protection-repair," thereby systematically delaying telomere shortening and achieving anti-aging effects.

[0006] The objective of this invention can be achieved through the following technical solutions: In a first aspect, an oral anti-aging composition based on telomere protection is provided, comprising the following components by weight: Cycloastragalol 15-25 parts; Astaxanthin 4-8 parts; Epigallocatechin gallate ester 200-400 parts; Nicotinamide ribose 200-400 parts; Vitamin D3 1500-2500 IU; Mixed nucleotides, 40-60 parts.

[0007] Furthermore, by weight, it contains the following components: Cycloastragalool 20 parts; Astaxanthin 6 parts; 300 parts of epigallocatechin gallate; 300 parts of nicotinamide ribose; Vitamin D3 2000 IU; 50 portions of mixed nucleotides.

[0008] Cycloastragalol acts as a transcriptional activator of the telomerase catalytic subunit (TERT) to activate telomerase; astaxanthin and epigallocatechin gallate act as stabilizers of telomere G-quadruplex structure and protectants against oxidative damage; nicotinamide ribose acts as an enhancer of telomere-specific DNA damage response and repair.

[0009] Furthermore, the mixed nucleotides are derived from yeast RNA.

[0010] Furthermore, by weight, it also includes 50-200 parts of yeast β-glucan.

[0011] Preferably, the yeast β-glucan is present in quantities of 80-150 parts.

[0012] Furthermore, the yeast β-glucan is β-1,3 / β-1,6-glucan.

[0013] The aging process is accompanied by immunosenescence and chronic inflammation, the latter of which exacerbates telomere wear. Yeast β-glucan can bind to the Dectin-1 receptor, activating immune cells and reducing chronic inflammation levels. Yeast β-glucan improves the immune microenvironment, creating conditions for telomere repair, while other components directly act on the activation, protection, and repair of telomeres.

[0014] Furthermore, the composition is an oral dietary supplement or functional food.

[0015] Furthermore, the oral dietary supplement is selected from one or more of tablets, capsules, granules, powders, and oral liquids. Secondly, the invention provides the application of an oral anti-aging composition based on telomere protection in the preparation of products for maintaining or increasing telomere length and delaying cell aging.

[0016] Furthermore, maintaining or increasing telomere length is achieved by synergistically enhancing telomerase activity, reducing telomere-specific oxidative damage, and strengthening telomere DNA damage repair.

[0017] Thirdly, an oral anti-aging pharmaceutical composition is provided, comprising the telomere-protected oral anti-aging composition of claim 1 and acceptable pharmaceutical excipients.

[0018] The beneficial effects of this invention are as follows: This invention contains cycloastragaloyl alcohol, which acts as a transcriptional activator of the telomerase catalytic subunit (TERT), effectively enhancing telomerase activity and actively elongating telomeric DNA, providing an "open source" of power for maintaining telomere length. However, if telomeric DNA already suffers from oxidative damage or structural instability, the elongation efficiency of telomerase will be significantly reduced. Therefore, while activating telomerase, the protection of telomere structure and the repair capacity of telomeric DNA damage are simultaneously strengthened. These three factors work synergistically to systematically delay or even reverse telomere shortening, directly intervening in the "molecular clock" of cellular aging. Specifically: (1) This invention comprises astaxanthin and epigallocatechin gallate (EGCG). Astaxanthin, as a potent antioxidant that crosses the blood-brain barrier and a telomere G-quadruplex stabilizer, has a unique molecular structure that allows it to embed into the cell membrane and mitochondrial membrane, quenching singlet oxygen and providing targeted protection for telomere DNA, a "hotspot" of oxidative damage. Epigallocatechin gallate, as a telomere G-quadruplex binding agent and epigenetic regulator, can specifically bind to and stabilize telomere G-quadruplexes, preventing them from abnormally unwinding or being attacked by nucleases, and influencing aging-related genes through epigenetic regulation. The two work synergistically to achieve physical protection of telomere structure and reduce the accumulation of telomere damage.

[0019] (2) This invention contains nicotinamide ribose (NR) and vitamin D3. NR acts as NAD+. + Precursor, capable of enhancing intracellular NAD + Level, thereby activating NAD + DNA repair is dependent on the enzymes SIRT6 and PARP1. SIRT6 is specifically recruited to telomere regions to promote DNA repair, while PARP1 is involved in the repair of telomere single-strand breaks. + It is an essential substrate for these two key repair enzymes, by increasing NAD+ +At the cellular level, this invention directly enhances the DNA damage repair capacity of cells (especially telomeres), which is key to reversing telomere shortening. Vitamin D3, as a positively correlated factor for telomere length and an immunomodulator, creates a favorable intracellular environment for telomere maintenance by systemically regulating inflammation and the cell cycle.

[0020] (3) This invention also includes mixed nucleotides (such as those from yeast RNA) to provide raw materials for telomere DNA synthesis. Telomeres are essentially DNA with TTAGGG repetitive sequences, and their replication and telomerase elongation require a sufficient pool of dNTPs (especially dGTPs and dTTPs). The dNTP pool may be imbalanced in senescent cells. This invention provides direct raw materials for telomere maintenance from a synthetic biology perspective by supplementing mixed nucleotides, complementing the telomerase activation strategy, and is particularly important in highly proliferating cells, achieving a "feeding" effect.

[0021] (4) This invention also includes yeast β-glucan. Yeast β-glucan alone has no direct effect on telomeres, but when combined with cycloastragalool, astaxanthin, EGCG, NR, mixed nucleotides, and vitamin D3, it can further enhance telomerase activity, reduce telomere oxidative damage, and maintain telomere length. It is known that yeast β-glucan can exert an immunomodulatory effect by binding to the Dectin-1 receptor on the surface of immune cells, and it may indirectly enhance the telomere protective effect of this invention by improving the body's immune microenvironment. In vitro cell experiments have shown that the full formulation containing yeast β-glucan is significantly better than the full formulation without yeast β-glucan in terms of increased telomerase activity, reduced telomere oxidative damage, and maintenance of telomere length (p<0.05). Attached Figure Description

[0022] To facilitate understanding by those skilled in the art, the present invention will be further described below with reference to the accompanying drawings.

[0023] Figure 1 This is a bar chart showing the relative telomerase activity of each group of cells in this invention; Figure 2 The bar chart shows the telomere comet tail moments (damage index) of each group of cells in this invention; Figure 3 The bar chart shows the average telomere fluorescence intensity (telomere length) of cells in each group according to the present invention. Figure 4 This is a bar chart showing the relative telomerase activity of groups H and J in this invention. Figure 5 This is a bar chart of the telomere comet tails of groups H and J in this invention; Figure 6 This is a bar chart showing the average telomere fluorescence intensity of groups H and J in this invention. Detailed Implementation

[0024] To further illustrate the technical means and effects of the present invention in achieving the intended purpose, the following detailed description of the specific implementation methods, structures, features and effects of the present invention, in conjunction with the accompanying drawings and preferred embodiments, is provided.

[0025] By using oral dietary supplements, telomere shortening can be prevented, aiming to achieve anti-aging and maintain a youthful appearance. Specifically, a compound formula works synergistically on three key aspects of telomere maintenance: telomerase activation, physical protection of telomere structure, and telomere DNA damage repair. This systematically delays or even reverses telomere shortening, aiming to directly intervene in the "molecular clock" of cellular aging. It advocates the synergistic effect of cycloastragalool (activating enzyme), astaxanthin / EGCG (protecting structure), and NR (enhancing repair) for superior telomere maintenance.

[0026] Example 1 Anti-aging composition formula: 20 parts cycloastragalool, 6 parts astaxanthin, 300 parts epigallocatechin gallate (EGCG), 300 parts nicotinamide ribose (NR), 2000 IU vitamin D3, and 50 parts mixed nucleotides (from yeast RNA).

[0027] Example 2 Anti-aging composition formula: 15 parts cycloastragalool, 4 parts astaxanthin, 200 parts epigallocatechin gallate (EGCG), 200 parts nicotinamide ribose (NR), 1500 IU vitamin D3, and 40 parts mixed nucleotides (from yeast RNA).

[0028] Example 3 Anti-aging composition formula: 25 parts cycloastragalool, 8 parts astaxanthin, 400 parts epigallocatechin gallate (EGCG), 400 parts nicotinamide ribose (NR), 2500 IU vitamin D3, and 60 parts mixed nucleotides (from yeast RNA).

[0029] Example 4 Anti-aging composition formula: 20 parts cycloastragalool, 6 parts astaxanthin, 300 parts epigallocatechin gallate (EGCG), 300 parts nicotinamide ribose (NR), 2000 IU vitamin D3, 50 parts mixed nucleotides (from yeast RNA), and 100 parts yeast β-glucan (β-1,3 / β-1,6-glucan).

[0030] Example 5 Anti-aging composition formula: 15 parts cycloastragalool, 4 parts astaxanthin, 200 parts epigallocatechin gallate (EGCG), 200 parts nicotinamide ribose (NR), 1500 IU vitamin D3, 40 parts mixed nucleotides (from yeast RNA), and 80 parts yeast β-glucan (β-1,3 / β-1,6-glucan).

[0031] Example 6 Anti-aging composition formula: 25 parts cycloastragalool, 8 parts astaxanthin, 400 parts epigallocatechin gallate (EGCG), 400 parts nicotinamide ribose (NR), 2500 IU vitamin D3, 60 parts mixed nucleotides (from yeast RNA), and 150 parts yeast β-glucan (β-1,3 / β-1,6-glucan).

[0032] Effect verification I. Taking Example 1 as an example, the effect of the anti-aging composition was verified.

[0033] In vitro effects of multi-pathway synergistic formulation on telomere maintenance 1. Experimental Objective This experiment aims to verify the synergistic effects of this compound formulation on three pathways—telomerase activation, telomere structure protection, and telomere damage repair—at the in vitro cellular level. By comparing the effects of single components, two-component combinations, and the full formulation, preliminary evidence is provided for the described synergistic mechanism.

[0034] 2. Experimental Materials Human umbilical cord mesenchymal stem cells (hUC-MSCs) were used to establish a hydrogen peroxide (H2O2)-induced acute oxidative stress cellular senescence model.

[0035] 3. Experimental Grouping Experimental group setup: Group A (control group): cultured in normal culture medium; Group B (model group): Oxidative damage was induced by a culture medium containing hydrogen peroxide.

[0036] Single component group: Group C (Cycloastragalol monotherapy group): Model group + cycloastragalol; Group D (Astaxanthin monotherapy group): Model group + Astaxanthin; Group E (NR-only group): Model group + nicotinamide riboside (NR).

[0037] Two-component group: Group F: Model group + Cycloastragalol + Astaxanthin; Group G: Model group + Cycloastragalol + Nicotinamide Ribose.

[0038] Full formulation set: Group H: Model group + Cycloastragalol + Astaxanthin + Epigallocatechin gallate + Nicotinamide ribose.

[0039] 4. Detection Method (1) Telomerase activity detection The total protein of cells in each group was extracted using the telomere repeat sequence amplification (TRAP)-real-time quantitative PCR (qPCR) kit, and the relative telomerase activity was detected (with the control group being 1.0).

[0040] (2) Assessment of telomere DNA oxidative damage The comet assay (single-cell gel electrophoresis) was employed, combined with telomere-specific peptide-nucleic acid fluorescence in situ hybridization (PNA-FISH) probes. Telomere signal intensity in the comet tail was analyzed to quantify telomere-specific DNA damage and detect telomere comet tail moments.

[0041] (3) Quantitative analysis of telomere length Quantitative fluorescence in situ hybridization (Q-FISH) was used to stain metaphase chromosomes with a telomere-specific (CCCTAA) 3PNA-Cy3 probe. The telomere length of a single chromosome was quantified by fluorescence intensity, and the average telomere fluorescence intensity (au) was detected.

[0042] 5. Experimental Results Table 1. Data on telomerase activity, telomere damage, and telomere length in each group of cells.

[0043] Statistical Explanation (1) Data processing: All data are expressed as mean ± standard deviation, and each group is an independent biological replicate n≥6.

[0044] (2) Statistical methods: One-way ANOVA combined with Tukey's multiple comparison test was used to analyze the differences between groups.

[0045] (3) Explanation of salience markers: ①*: Compared with the model group (H2O2), p <0.05, p <0.01, p <0.001; ②#: Compare with the corresponding core single-component or two-component combination. p <0.05.

[0046] For "relative telomerase activity" and "average telomere fluorescence intensity", "#" indicates that the full formulation group (or the cycloastragalool + NR group) is significantly better than the cycloastragalool monotherapy group.

[0047] For "telomere comet tail moment", "#" indicates that the full formulation group (or the cycloastragalol + astaxanthin group) is significantly better than the astaxanthin-only group.

[0048] In summary, # indicates a comparison between the full-formula group, the cycloastragalool + NR group, and the cycloastragalool monotherapy group; and the full-formula group, the cycloastragalool + astaxanthin group, and the astaxanthin monotherapy group. p <0.05.

[0049] 6. Experimental Conclusions Table 1 Figures 1-3 The data results show that (1) Multi-pathway synergistic effect Data shows that the full-formulation group achieved the best results in three aspects: relative telomerase activity increase (1.95-fold), reduction of telomere oxidative damage (tail moment 10.5), and maintenance of telomere length (9600 au), and was generally superior to any single-component group or dual-component group. This indicates that its three-dimensional synergistic mechanism, namely the strategy of simultaneously "opening up" (activating enzyme), "reducing" (reducing damage), and "repairing" (repairing damage), is more effective in telomere repair than a single strategy.

[0050] (2) Functional analysis of each module Telomerase activation module: Astragaloside alone significantly increased enzyme activity (1.65), indicating that it does indeed act as a transcriptional activator of the telomerase catalytic subunit (TERT), i.e., telomere repair. However, the activity was even higher when used in combination with NR (astragaloside + NR group) (1.80), suggesting that NR provides NAD+. + It may indirectly support the function of telomerase by improving the cellular metabolic environment.

[0051] Terminal structure protection module: Astaxanthin alone showed the most significant effect in reducing telomere-specific damage (tail moment decreased from 28.5 to 15.3), demonstrating its targeted protective role as a "powerful antioxidant and telomere G-quadruplex stabilizer". When used in combination with cycloastragalol (cycloastragalol + astaxanthin), it better maintained telomere length while protecting telomeres.

[0052] Damage Repair and Metabolic Support Module: NR alone has a certain effect on maintaining telomere length. More importantly, in the entire formulation, it works synergistically with protective ingredients, potentially by increasing NAD+. + At this level, it activates repair enzymes such as SIRT6 and PARP1, thereby playing a key "repair-enabling" role in treating oxidative damage and maintaining telomere integrity.

[0053] The full-formulation group showed the best results in all three indicators: increasing telomerase activity, reducing telomere damage, and maintaining telomere length. It was significantly better than most single-component groups and some dual-component combination groups, which strongly verified the design concept and synergistic effect of the "activation-protection-repair" multi-pathway synergy.

[0054] II. Taking Example 4 as an example, we further verified the synergistic effect of the whole formula on telomere maintenance after adding yeast β-glucan.

[0055] 1. Experimental materials Similar to Example 1, human umbilical cord mesenchymal stem cells were used to establish a hydrogen peroxide-induced acute oxidative stress cell senescence model.

[0056] 2. Experimental Grouping Control group: cultured in normal culture medium; Model group: Oxidative damage induced by hydrogen peroxide-containing culture medium; Group I (Yeast β-glucan alone): Model group + yeast β-glucan; Group H (Full Formula Group 1): Model Group + Cycloastragalol + Astaxanthin + Epigallocatechin Gallate + Nicotinamide Riboside; Group J (Full Formula Group 2): Model Group + Cycloastragalool + Astaxanthin + Epigallocatechin Gallate + Nicotinamide Ribose + Yeast β-Glucan.

[0057] 3. Detection Method Same as in Example 1, relative telomerase activity, telomere comet tail moment, and average telomere fluorescence intensity were detected.

[0058] 4. Experimental Results Table 2 Figures 4-6 The data results show that Table 2. Data on telomere-related indicators in the full formulation group containing yeast β-glucan.

[0059] Note: *** indicates that groups H and J are compared with the model group. p <0.001; # indicates that group J is compared to group H. p <0.05.

[0060] 5. Experimental Results (1) Yeast β-glucan single use group (Group I): Compared with the model group, there were no significant differences in telomerase relative activity, telomere comet tail moment and average telomere fluorescence intensity. p >0.05), indicating that yeast β-glucan itself has no direct and significant effect on telomere length and telomerase activity.

[0061] (2) Compared with group H, group J: The relative activity of telomerase increased significantly from 1.95 to 2.18; the telomere comet tail moment decreased significantly from 10.5 to 8.2; and the average telomere fluorescence intensity increased significantly from 9600 to 10200.

[0062] Yeast β-glucan alone has no significant effect on telomeres, but when combined with the composition of the present invention, it can further significantly enhance telomerase activity, reduce telomere oxidative damage, and maintain telomere length.

[0063] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. An oral anti-aging composition based on telomere protection, characterized in that, By weight, it contains the following components: Cycloastragalol 15-25 parts; Astaxanthin 4-8 parts; Epigallocatechin gallate ester 200-400 parts; Nicotinamide ribose 200-400 parts; Vitamin D3 1500-2500 IU; Mixed nucleotides, 40-60 parts.

2. The oral anti-aging composition based on telomere protection according to claim 1, characterized in that, By weight, it contains the following components: Cycloastragalool 20 parts; Astaxanthin 6 parts; 300 parts of epigallocatechin gallate; 300 parts of nicotinamide ribose; Vitamin D3 2000 IU; 50 portions of mixed nucleotides.

3. The oral anti-aging composition based on telomere protection according to claim 1 or 2, characterized in that, The mixed nucleotides were derived from yeast RNA.

4. The oral anti-aging composition based on telomere protection according to claim 1 or 2, characterized in that, It also includes 50-200 parts by weight of yeast β-glucan.

5. The oral anti-aging composition based on telomere protection according to claim 4, characterized in that, The yeast β-glucan is β-1,3 / β-1,6-glucan.

6. The oral anti-aging composition based on telomere protection according to claim 1, characterized in that, The composition is an oral dietary supplement or functional food.

7. The oral anti-aging composition based on telomere protection according to claim 6, characterized in that, The oral dietary supplement is selected from one or more of the following: tablets, capsules, granules, powders, and oral liquids.

8. The use of the oral anti-aging composition based on telomere protection according to any one of claims 1 to 7 in the preparation of products for maintaining or increasing telomere length and delaying cell aging.

9. The use of the oral anti-aging composition based on telomere protection according to claim 8 in the preparation of products for maintaining or increasing telomere length and delaying cell aging, characterized in that, Maintaining or increasing telomere length is achieved by synergistically enhancing telomerase activity, reducing telomere-specific oxidative damage, and strengthening telomere DNA damage repair.

10. An oral anti-aging pharmaceutical composition, characterized in that, This includes the oral anti-aging composition based on telomere protection as described in any one of claims 1 to 7, and acceptable pharmaceutical excipients.

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