Aging inhibitor, composition and food and drink containing aging inhibitor, short lifespan inhibitor, and fatty liver inhibitor

Abstract

Provided are an anti-aging agent capable of suppressing one or more physical symptoms of aging in mammals, a composition containing the anti-aging agent, a food containing the anti-aging agent, an anti-short lifespan agent capable of suppressing short lifespan, and an anti-fatty liver agent capable of suppressing fatty liver. [Solution] An aging inhibitor that suppresses one or more physical symptoms of aging in mammals, containing one or more of pyrroloquinoline quinone, imidazopyrroloquinoline quinone and / or salts thereof as an active ingredient, a composition containing the aging inhibitor, a food product containing the aging inhibitor, and a short-lifespan inhibitor or fatty liver inhibitor that contains one or more of pyrroloquinoline quinone, imidazopyrroloquinoline quinone and / or salts thereof as an active ingredient.

Description

[Technical Field]

[0001] The present invention relates to an anti-aging agent, a composition and food and drink containing the anti-aging agent, an anti-aging agent for short life span, and an anti-fatty liver agent. [Background technology]

[0002] Aging is the greatest risk factor for deteriorating health. Aging can cause symptoms such as decreased liver function, muscle weakness, and deterioration of hair condition, but the greatest risk associated with aging is death. Suppressing the symptoms of aging is extremely important, as it can lead to an extension of healthy lifespan.

[0003] Pyrroloquinoline quinone is a coenzyme, and pyrroloquinoline quinone disodium is available as a food product. The lifespan extension effect of pyrroloquinoline quinone disodium has been reported (Patent Document 1).

[0004] Although there is little knowledge about imidazopyrroloquinolines, it is known that, for example, there is an active oxygen scavenger containing an imidazopyrroloquinoline compound as an active ingredient (Patent Document 2), and that imidazopyrroloquinolines have no lifespan extension effect in nematode tests (Non-Patent Document 1).

[0005] Aging can also make it more difficult to absorb nutrients, resulting in a loss of body fat. However, at the same time, visceral fat, especially in the liver, can accumulate. Fat accumulation in the liver can impair liver function, so it is important to prevent this. Ideally, it would be desirable to prevent a loss of body fat with aging and maintain a state in which visceral fat, especially in the liver, is suppressed, and effective methods for achieving this are needed. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Patent No. 6609261 [Patent Document 2] Japanese Patent Application Publication No. 10-45594 [Non-patent literature]

[0007] [Non-Patent Document 1] J Cell Sci. 2017 Aug 1;130(15):2631-2643. doi: 10.1242 / jcs.202119. Summary of the Invention [Problem to be solved by the invention]

[0008] However, it is not known that pyrroloquinoline quinone, imidazopyrroloquinoline quinone, and salts thereof can suppress short lifespan or local accumulation of visceral fat.

[0009] Furthermore, at present, there are no known substances that are effective in suppressing or improving aging symptoms such as muscle weakness and deterioration of hair condition.

[0010] Furthermore, although there are many hereditary aging diseases, the effects of pyrroloquinoline quinone, imidazopyrroloquinoline quinone, and their salts on these diseases have not been clear. Although research on hereditary aging has been conducted using mice with progeria, no research has been conducted on pyrroloquinoline quinone, imidazopyrroloquinoline quinone, and their salts using mice with progeria.

[0011] As a result of extensive research, the present inventors have found that pyrroloquinoline quinone, imidazopyrroloquinoline quinone, and salts thereof can suppress one or more physical symptoms of aging in mammals, and have thus completed the present invention.

[0012] The object of the present invention is to provide an anti-aging agent capable of suppressing one or more physical symptoms of aging in mammals, a composition containing an anti-aging agent, a food or beverage containing an anti-aging agent, an anti-short lifespan agent capable of suppressing short lifespan, and an anti-fatty liver agent capable of suppressing fatty liver. [Means for solving the problem]

[0013] In order to achieve the above object, the present invention provides the following aging inhibitor, composition, food and drink, short lifespan inhibitor, and fatty liver inhibitor.

[0014] [1] An anti-aging agent that suppresses one or more physical symptoms of aging in mammals, comprising one or more of pyrroloquinoline quinone, imidazopyrroloquinoline quinone and / or salts thereof as an active ingredient. [2] The anti-aging agent according to [1], wherein the physical symptoms are short-lived. [3] The anti-aging agent according to [1], wherein the physical symptom is fatty liver. [4] The anti-aging agent according to [1], wherein the physical symptom is muscle weakness. [5] The anti-aging agent according to [1], wherein the physical symptom is hair deterioration. [6] The anti-aging agent according to [1], which contains pyrroloquinoline quinone and / or a salt thereof as the active ingredient. [7] The anti-aging agent according to [1], which contains imidazopyrroloquinoline quinone and / or a salt thereof as the active ingredient. [8] The anti-aging agent according to [1], which contains, as the active ingredient, a disodium salt of pyrroloquinoline quinone and / or a disodium salt of imidazopyrroloquinoline quinone. [9] A composition comprising the anti-aging agent according to any one of [1] to [8] above.

[10] A food or drink containing the anti-aging agent according to any one of [1] to [8] above.

[11] A short lifespan inhibitor for suppressing short lifespan in mammals, comprising one or more of pyrroloquinoline quinone, imidazopyrroloquinoline quinone and / or salts thereof as an active ingredient.

[12] A fatty liver inhibitor that suppresses fatty liver in mammals, comprising one or more of pyrroloquinoline quinone, imidazopyrroloquinoline quinone, and / or salts thereof as an active ingredient. [Effects of the Invention]

[0015] According to the present invention, it is possible to provide an aging inhibitor capable of suppressing one or more physical symptoms of aging in mammals, a composition containing an aging inhibitor, a food or beverage containing an aging inhibitor, a short lifespan inhibitor capable of suppressing short lifespan, and a fatty liver inhibitor capable of suppressing fatty liver. [Brief explanation of the drawings]

[0016] [Figure 1] 1 is a graph showing changes in body weight over time in an example and a comparative example. [Figure 2] 1 is a graph showing the change in food intake over time in an example and a comparative example. [Figure 3] 1 is a graph showing the results of analysis of survival rates in Examples and Comparative Examples. [Figure 4] 1 shows optical microscope photographs of liver tissues from an example and a comparative example. [Figure 5] 1 is a graph showing the results of an analysis of the oil droplet size of fat present in the liver of an example and a comparative example. [Figure 6] 1 is a graph showing changes in muscle strength in an example and a comparative example. DETAILED DESCRIPTION OF THE INVENTION

[0017] Hereinafter, embodiments for carrying out the present invention will be described in detail, but the present invention is not limited to these, and various modifications are possible within the scope of the gist of the present invention.

[0018] [Aging inhibitors] The anti-aging agent according to an embodiment of the present invention (hereinafter referred to as "the present embodiment") suppresses one or more physical symptoms of aging in mammals, and contains one or more of pyrroloquinoline quinone (PQQ), imidazopyrroloquinoline quinone (IPQ), and / or salts thereof as an active ingredient.

[0019] (PQQ) The PQQ used in this embodiment is a compound having the chemical structure shown in the following formula (Chemical Formula 1). [ka]

[0020] The PQQ used in this embodiment may be the oxidized PQQ shown in the above formula, or may be the reduced PQQ having the chemical structure shown in the following formula (Chemical Formula 2): The reduced PQQ is produced by reducing the oxidized PQQ in an aqueous solution. [ka]

[0021] PQQ may be used in the form of a salt. A PQQ salt is one in which one to three of the carboxyl groups in the above formula form a salt with an alkali metal ion or the like. The PQQ salt is not particularly limited, but examples include alkali metal salts such as sodium and potassium (specifically, PQQ sodium, PQQ potassium, etc.), alkaline earth metal salts such as calcium and magnesium (specifically, PQQ calcium, PQQ magnesium, etc.), PQQ aluminum, PQQ zinc, PQQ manganese, and PQQ iron. Among these, preferred PQQ salts are sodium PQQ and calcium PQQ. In particular, monosodium, disodium, and trisodium salts can be used, with pyrroloquinoline quinone disodium being easily available and easy to use.

[0022] PQQ and its salts may be used in the form of a solvate, such as a hydrate, preferably a monohydrate to trihydrate.

[0023] PQQ and its salts may be used alone or in combination of two or more.

[0024] There are no particular limitations on how PQQ and its salts are obtained; they may be naturally derived from animals or plants, or may be obtained by chemical synthesis or fermentation. A suitable method for producing PQQ and its salts can be appropriately selected based on the purity and production cost of the resulting PQQ and its salts. Commercially available PQQ and its salts can also be used as PQQ and its salts. Examples of such commercially available products include those manufactured or sold by Mitsubishi Gas Chemical Company, Inc. In this embodiment, PQQ or a composition containing PQQ obtained by culturing bacteria (such as PQQ bacteria) using a fermentation method can be used directly or after granulation.

[0025] Since PQQ and its salts are designated as foods in Japan and can be used as foods and drinks, it can be said that the anti-aging agent according to this embodiment is sufficiently safe for animals such as humans.

[0026] (IPQ) The IPQ used in this embodiment is a compound having the chemical structure shown in the following formula (Chemical Formula 3). In IUPAC nomenclature, it is represented as 7-oxo-7,10-dihydroimidazo[4,5,1-ij]pyrrolo[2,3-f]quinoline-1,3,9-tricarboxylic acid. [ka]

[0027] IPQ may be used in the form of a salt. The salt of IPQ is formed by the carboxyl group forming a salt with an alkali metal ion or the like. The salt of IPQ is not particularly limited, but examples thereof include alkali metal salts such as sodium and potassium (specifically, IPQ sodium, IPQ potassium, etc.), alkaline earth metal salts such as calcium and magnesium (specifically, IPQ calcium, IPQ magnesium, etc.), IPQ aluminum, IPQ zinc, IPQ manganese, and IPQ iron. Of these, IPQ sodium and IPQ calcium are preferred. In particular, monosodium, disodium, and trisodium salts can be used as the sodium salt, and imidazopyrroloquinoline quinone trisodium is easily available and easy to use.

[0028] IPQ and its salts may be used in the form of a solvate, such as a hydrate, preferably a monohydrate to trihydrate.

[0029] IPQ and its salts may be used alone or in combination of two or more.

[0030] There are no particular limitations on how IPQ and its salts are obtained; they may be naturally derived from animals or plants, or may be obtained by chemical synthesis or fermentation. A suitable method for producing IPQ and its salts can be selected based on the purity and production cost of the resulting IPQ and its salts. Commercially available IPQ and its salts can also be used. Examples of such commercially available products include those manufactured or sold by Mitsubishi Gas Chemical Company, Inc.

[0031] (Aging symptoms) The anti-aging agent of this embodiment suppresses one or more physical symptoms of aging in mammals, preferably suppresses two or more physical symptoms, more preferably suppresses three or more physical symptoms, and even more preferably suppresses four or more physical symptoms.

[0032] In this embodiment, examples of physical symptoms of mammalian aging include short lifespan, fatty liver, muscle weakness, hair deterioration, loss of body fat, decreased endurance, and skin deterioration. The aging inhibitor of this embodiment is particularly effective against short lifespan, fatty liver, muscle weakness, and / or hair deterioration. Here, short lifespan refers to an individual belonging to a species, genus, or family (e.g., human, dog, cat) having a shorter lifespan than the average lifespan of that species, genus, or family. Average lifespans may also vary by region. Factors contributing to this include, but are not limited to, genetic, environmental, and physiological factors. The aging inhibitor of this embodiment is particularly effective against short lifespans due to genetic factors. The aging inhibitor of this embodiment can be used as a short lifespan inhibitor, preferably as a genetic short lifespan inhibitor.

[0033] In addition, in a preferred embodiment of the present invention, the accumulation of liver fat is suppressed but the accumulation of body fat is not suppressed.

[0034] The anti-aging agent of the present embodiment can be used as a fatty liver inhibitor and can inhibit the phenomenon of fat accumulation in the liver without the accompanying loss of body fat that accompanies aging. Progression of fatty liver can lead to hepatitis or cirrhosis. Cirrhosis is a serious, potentially life-threatening condition in which liver function is significantly impaired, and this agent can inhibit this condition.

[0035] The anti-aging agent of this embodiment is effective against muscle weakness associated with aging. Aging causes muscle weakness, but the anti-aging agent of this embodiment can inhibit this.

[0036] The anti-aging agent of the present embodiment is effective in improving the condition of skin and hair associated with aging. Aging deteriorates the condition of the skin and causes hair loss, but the anti-aging agent of the present embodiment can inhibit these problems.

[0037] Suppression of physical symptoms includes suppression of the onset of symptoms, reduction or alleviation of symptoms, delay in the progression of symptoms, suppression of the worsening of symptoms, etc. In particular, although the mechanism of suppression of short lifespan is not clear, it is possible to suppress short lifespan by suppressing the onset of the symptom of short lifespan, reducing symptoms, or delaying the progression of symptoms, and to bring short-lived individuals, whose lifespan is shorter than the average lifespan, closer to the average lifespan, and preferably to extend their lifespan beyond the average lifespan.

[0038] In this embodiment, the mammal is preferably a placental mammal, ie, a eutherian animal, and particularly preferred species include mice, rats, humans, monkeys, chimpanzees, dogs, cats, cows, horses, pigs, sheep, and goats. The method is particularly effective in animals that are genetically prone to aging. Among mice, SAM mice are prone to aging. Larger dogs tend to have shorter lifespans. In humans, this condition is known as progeria, in which aging-like symptoms are seen earlier than the actual age, starting at a young age.

[0039] The anti-aging agent according to the present embodiment is not particularly limited as long as it is used to suppress physical symptoms of aging, and can be used, for example, as a food, functional food, pharmaceutical, or quasi-drug for humans or animals. The term "functional food" as used herein refers to a food taken for the purpose of maintaining health or supplementing nutrition in place of a meal, such as a health food, nutritional supplement, nutritional functional food, or nutritional health food. Specific forms include, but are not limited to, capsules, tablets, chewable tablets, and drinks. Among these, the agent according to the present embodiment is preferably taken orally as a drink (beverage), capsules such as soft capsules, or tablets.

[0040] The anti-aging agent of this embodiment is useful as a medicine, food, etc., and its application target may be mammals. Examples of such mammals include primates (e.g., humans, monkeys, chimpanzees), rodents (e.g., mice, rats, guinea pigs), pets (e.g., dogs, cats, rabbits), working animals or livestock (e.g., cows, horses, pigs, sheep, goats). The dosage (intake) of the anti-aging agent of this embodiment may be adjusted appropriately depending on the body weight or size of the animal.

[0041] [Composition] The composition according to this embodiment contains the anti-aging agent according to this embodiment. The anti-aging agent according to the present embodiment can be formulated into a composition by a conventional method using a pharmaceutically acceptable carrier as needed for formulation (hereinafter referred to as the "composition of the present embodiment"). The composition of the present embodiment contains the anti-aging agent of the present embodiment, and therefore can have all of the effects exhibited by the anti-aging agent of the present embodiment.

[0042] The carrier can be appropriately selected depending on the dosage form of the preparation (composition), and is not particularly limited, and examples thereof include additives such as excipients, binders, lubricants, disintegrants, solvents, stabilizers, solubilizers, antioxidants, colorants, flavoring agents, and sweeteners.

[0043] The excipient is not particularly limited, but examples thereof include sugars (white sugar, lactose, glucose, mannitol, etc.), starch (corn starch, etc.), crystalline cellulose, calcium phosphate, calcium sulfate, magnesium sulfate, etc.

[0044] The binder is not particularly limited, but examples thereof include pregelatinized starch, gelatin, tragacanth gum, gum arabic, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, crystalline cellulose, hydroxypropyl cellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, and polyvinyl alcohol.

[0045] The lubricant is not particularly limited, but examples thereof include magnesium stearate, talc, polyethylene glycol, silica, and hydrogenated vegetable oil.

[0046] The disintegrant is not particularly limited, but examples thereof include starch, crystalline cellulose, carboxymethyl cellulose, agar, calcium citrate, calcium carbonate, sodium bicarbonate, dextrin, and the like.

[0047] The solvent is not particularly limited, but examples thereof include water, ethanol, glycerol, saline, soybean oil, and the like.

[0048] The stabilizer is not particularly limited, but examples thereof include benzoic acid, sodium benzoate, ethyl parahydroxybenzoate, and propylene glycol.

[0049] The solubilizing agent is not particularly limited, but examples thereof include fumaric acid, succinic acid, and malic acid.

[0050] The antioxidant is not particularly limited, but examples thereof include ascorbic acid, tocopherol, sodium hydrogen sulfite, sodium thiosulfate, sodium pyrosulfite, and citric acid.

[0051] The coloring agents, flavoring agents, and sweetening agents include those that are generally permitted to be added in the pharmaceutical and food fields.

[0052] The content of one or more of PQQ, IPQ, and / or salts thereof in the composition of this embodiment is preferably 0.10 to 99.99% by mass, more preferably 0.60 to 99.90% by mass, and even more preferably 1.00 to 99.90% by mass, based on the total weight of the composition of this embodiment. The content of one or more of PQQ, IPQ, and / or salts thereof in the agent of this embodiment is treated as the weight of the substance. Therefore, there is no need to convert PQQ or IPQ salts into their free forms (free forms). Furthermore, when PQQ or IPQ salts form hydrates, the weight is calculated in the form including water molecules.

[0053] The composition of the present embodiment can be used as a medicine (i.e., a pharmaceutical composition). In this case, the pharmaceutical composition of the present embodiment can be used as a drug for preventing or treating physical symptoms of aging, such physical symptoms being as described above.

[0054] The method of administration of the pharmaceutical composition of this embodiment is not particularly limited, and generally includes oral administration, but parenteral administration (intravascular (intravenous, intraarterial) administration, subcutaneous administration, transdermal administration, rectal administration, etc.) may be appropriately selected depending on the condition, severity, etc. of the target patient. In this embodiment, oral administration is preferably adopted.

[0055] The dosage form of the pharmaceutical composition of this embodiment is not particularly limited and can be a form suitable for the administration method. Examples of forms suitable for oral administration include tablets, lozenges, hard or soft capsules, aqueous or oily suspensions, emulsions, dispersible powders or granules, syrups, or elixirs. Examples of forms suitable for parenteral administration include, for example, forms suitable for parenteral injection, such as sterile solutions, suspensions, and emulsions for intravenous, subcutaneous, intramuscular, intravascular, or infusion administration, and forms suitable for transdermal administration, such as creams, ointments, gels, and aqueous or oily solutions (including suspensions).

[0056] The composition of the present embodiment can also be used as a food or beverage (i.e., a food or beverage composition). In this case, the food or beverage composition of the present embodiment can be formulated by a conventional method using a carrier commonly used in the field of food or beverage in addition to the above-mentioned pharmaceutically acceptable carrier.

[0057] In this embodiment, the term "food and beverages" refers to food and beverages in general, but also includes general foods including so-called health foods, as well as special purpose foods specified by the Consumer Affairs Agency (such as foods for specified health uses, foods for the sick, and foods for people with swallowing difficulties) and functional foods, and further includes supplements, feed, etc.

[0058] The dosage form of the food and beverage composition of this embodiment is not particularly limited, and may be in the form of fine granules, granules, pills, tablets (including coated tablets and sugar-coated tablets), capsules (including hard capsules, soft capsules and microcapsules), beverages, drinks, liquids (including syrups, emulsions and suspensions), powdered foods, jellies, candies and the like.

[0059] The dosage (intake) of the agent and composition of this embodiment is not particularly limited, and may be within an effective amount range capable of exerting an inhibitory effect on physical symptoms of aging in the body, and may be appropriately set depending on individual differences in the subject, symptoms, administration method, etc. Furthermore, the dosage (intake) per day may be administered (ingested) all at once or divided into several times (e.g., two or three times). The agent and composition of this embodiment may be administered (ingested) before, after, or between meals, and the duration is not particularly limited as long as the effects of this embodiment are achieved. Hereinafter, when the term "administration" is used in this specification, this term is meant to encompass the concept of "ingestion."

[0060] As described above, PQQ and / or a salt thereof and IPQ and / or a salt thereof can be formulated into separate preparations, in which case both preparations can be used together in this embodiment. PQQ and / or a salt thereof and IPQ and / or a salt thereof can be administered simultaneously or sequentially in any order.

[0061] When using the agent and composition of this embodiment, if there is an existing ingredient that has an effect of suppressing physical symptoms of aging, such as an effect of suppressing short lifespan, an effect of suppressing fatty liver, an effect of suppressing muscle weakness, or an effect of improving skin and hair, it can also be used in combination with such an ingredient. In such cases, the order in which the agent and composition of this embodiment and the existing ingredient are administered may be simultaneous or separate. If administered separately, the agent and composition of this embodiment may be administered either before or after the existing ingredient.

[0062] [Short-life inhibitor] The short lifespan suppressor according to this embodiment is an agent for suppressing short lifespan in mammals, which contains one or more of pyrroloquinoline quinone, imidazopyrroloquinoline quinone and / or salts thereof as an active ingredient. The definitions of the terms, the contents, etc. are as described above. The anti-aging agent can also be used as a composition.

[0063] [Fatty liver inhibitors] The fatty liver inhibitor according to this embodiment is an agent for inhibiting fatty liver in mammals, which comprises one or more of pyrroloquinoline quinone, imidazopyrroloquinoline quinone and / or salts thereof as an active ingredient. The definitions of the terms, the contents, etc. are as described above. The anti-aging agent can also be used as a composition. [Example]

[0064] The present invention will be explained in more detail below by way of examples, but these are merely illustrative and do not limit the scope of the present invention in any way.

[0065] <Experimental materials> The pyrroloquinoline quinone disodium salt used in this example was BioPQQ (hereinafter also referred to as "PQQ") manufactured by Mitsubishi Gas Chemical Co., Ltd. Unless otherwise specified, reagents manufactured by Wako Pure Chemical Industries, Ltd. were used for other compounds.

[0066] The imidazopyrroloquinoline quinone trisodium salt (Na3IPQ) used in this example was prepared according to the following method. 25 g (58.4 mmol) of pyrroloquinoline quinone disodium salt (BioPQQ), 50 g of glycine, 50 g of NaCO, and 2.5 L of water were stirred and reacted for 20 hours while blowing air at 1 L / min. The precipitated solid was filtered to obtain 59.7 g of a wet cake (HPLC purity 98.9%). The obtained wet cake was purified as follows. The wet cake was added to 1 L of water and heated to above 80°C to dissolve. It was filtered while still hot (filter paper No. 2). While still warming, 500 mL of 20 wt% aqueous sodium chloride was added to the filtrate, after which heating was stopped. After standing overnight, it was filtered and washed with ethanol to obtain 46.5 g of cake (HPLC purity 99.3%). This cake was added to 1 L of water and heated to above 70°C to dissolve. It was filtered while still hot (filter paper No. 2). While still warming, 1 L of 1 M sodium chloride (59 g / L) was added to the filtrate, after which heating was stopped. After standing overnight, it was filtered and washed with 80 mL of 50% aqueous ethanol. The cake was dried under reduced pressure to obtain 19.9 g of solid Na3IPQ (Mw 407.18) (water 24.6%, HPLC purity 99.6%) in a 67% yield. The obtained Na3IPQ was analyzed as follows.

[0067] [1H-NMR (heavy water, internal standard TSP)] The analysis was carried out using a JNM-ECA500 JEOL nuclear magnetic resonance analyzer. 4.3 mg of sample was dissolved in 0.7 mL of heavy water (99.9%, manufactured by WAKO). 1 mg of sodium trimethylsilylpropionate was added as an internal standard. 32 integrated measurements were carried out. As a result, peaks were observed at 7.30, 8.22, and 9.39 ppm (0 ppm is the internal standard, and 4.80 ppm is the heavy water peak). From these results, it was determined that the structure was IPQ.

[0068] <Manufacturing compound feed> Example 1: AIN-93M was mixed with 0.02% by mass of BioPQQ. Example 2: 0.02% by mass of the prepared Na3IPQ was blended into AIN-93M. Comparative Example 1: AIN-93M only

[0069] [AIN-93M feed composition] AIN-93M: Quoted from "Feeds for Laboratory Animals, Oriental Yeast Co., Ltd." [Calories] 3582 kcal / kg, [Ingredients] Total protein (12.6%), total fat (4.0%), total carbohydrates (72.7%), moisture (6.8%), [Ingredients] Casein (14.0%), L-cystine (0.18%), corn with neral (3.5%), AIN-93 vitamin mix (1.0%), choline bitartrate (0.25%), tert-butylhydroquinone (0.0008%)

[0070] <Mouse used> The mice used were SPF (germ-free) senescence-accelerated mouse (SAM) P8 strain SAMP8 / Toho (established at Toho University) mice, maintained at the Laboratory Animal Center, Faculty of Pharmaceutical Sciences, Toho University. They were housed at 23°C ± 1°C with a 12-hour light-dark cycle, with no more than five mice in a 32 × 22 × 12 cm cage. During the weaning period (23 days after birth), mice were fed Ce-7 diet (manufactured by CLEA Japan). Body weight and body composition were measured, and the mice were divided into the following three groups so that their averages were similar. After the weaning period (24 days after birth), measurements of body weight and food intake (changes over time) and the following evaluation tests (suppression of short lifespan, coat condition) were initiated. Each group was allowed to freely consume the test diets (Examples 1-2, Comparative Example 1) until death. Tap water was provided in a water bottle (CK-200S, CLEA Japan, Inc.) and was provided ad libitum. Tap water was changed at least twice a week. [Grouping] Example 1 16 animals Example 2 15 animals Comparative Example 1: 15 fish

[0071] <Body weight and food intake (changes over time)> Body weight and food intake were measured continuously weekly for each group. Figure 1 shows a graph of body weight change over time. Data are shown as mean ± standard deviation. Figure 2 also shows a graph of food intake change over time. Data are shown as mean values. The body weights of the mice in Examples 1 and 2 were 1.1 times that of the mice in Comparative Example 1. On the other hand, there was no difference in food intake between the Comparative Example and the Examples, and no difference was observed among the three groups. Therefore, it can be said that nutritional disorders due to aging were suppressed in the Examples.

[0072] <Evaluation of short-life suppression> The survival rate was analyzed for each group, and the results are shown in Table 1 and Figure 3.

[0073] 3, it can be seen that the Examples have a superior effect of suppressing short lifespan compared to the Comparative Examples (up to a survival rate of about 50%). In particular, it can be seen that the Examples have a remarkable effect of suppressing short lifespan up to a survival rate of about 60 to 70%.

[0074] [Table 1]

[0075] <Coat condition evaluation> Photographs were taken at the start of the test and 9 months after the start of the test, and the coat texture was compared. The average value at the start of the test (immediately after weaning) was calculated, and this was set as the initial value of 100. Evaluation was done in increments of 20 points (100: very good, 80: good, 60: fair, 40: poor, 20: very poor, hair loss observed, 0: dead). The results are shown in Table 2. Compared to Comparative Example 1, both Examples 1 and 2 maintained a lustrous coat texture.

[0076] [Table 2]

[0077] <Metabolism-related experiments> SAMP8 / Toho mice were used, and the following test diets were fed to mice aged 39 to 49 weeks, which corresponds to middle-aged and elderly mice, to observe the effects. Liver tissue was observed at 49 weeks of age. Example 3: AIN-93M was mixed with 0.02% by mass of BioPQQ. Example 4: 0.02% by mass of the prepared Na3IPQ was blended into AIN-93M. Comparative Example 2: AIN-93M only

[0078] In the same manner as in Examples 1 and 2 and Comparative Example 1, the samples were divided into the following three groups. [Grouping] Example 3 14 animals Example 4 13 animals Comparative Example 2: 13 animals

[0079] [Liver tissue observation] Liver tissue was sliced ​​and observed. Photographs were taken (Figure 4), and the image analysis software Image J was used to analyze the size of the lipid droplets present in the liver, and the results were graphed (Figure 5). The right photograph is an enlargement of the boxed area in the left photograph of Figure 4. The dotted areas represent fat. The amount of fat present in the livers of Examples 3 and 4 was less than that of Comparative Example 2. The size of the lipid droplets was also smaller.

[0080] Considering the change in body weight, it is expected that the body weight of the Example was greater than that of the Comparative Example, and that there would be more fat accumulation. However, in reality, fat accumulation in the liver was suppressed. It can be seen that the present invention is able to suppress localized fat accumulation.

[0081] <Muscle strength measurement> The mice used in the metabolism-related experiments were subjected to a pole grip test at 49 weeks of age before the liver tissue observation. Mice were asked to hold onto a high horizontal pole and the duration of their holding (time until they fell) was measured. 6 shows the change in muscle strength, with the initial muscle strength set at 100. In both Examples 3 and 4, the muscle strength was found to increase significantly compared to Comparative Example 2.

Claims

1. An anti-aging agent for suppressing one or more physical symptoms of aging in mammals, comprising one or more of pyrroloquinoline quinone, imidazopyrroloquinoline quinone and / or salts thereof as an active ingredient.

2. The anti-aging agent according to claim 1, wherein the physical symptoms are short-lived.

3. The anti-aging agent according to claim 1, wherein the physical symptom is fatty liver.

4. The anti-aging agent according to claim 1, wherein the physical symptom is muscle weakness.

5. The anti-aging agent according to claim 1, wherein the physical symptom is hair deterioration.

6. The anti-aging agent according to claim 1, comprising pyrroloquinoline quinone and / or a salt thereof as the active ingredient.

7. The anti-aging agent according to claim 1, comprising imidazopyrroloquinoline quinone and / or a salt thereof as the active ingredient.

8. 2. The anti-aging agent according to claim 1, comprising, as the active ingredient, a disodium salt of pyrroloquinoline quinone and / or a disodium salt of imidazopyrroloquinoline quinone.

9. A composition comprising the aging inhibitor according to any one of claims 1 to 8.

10. A food or drink comprising the aging inhibitor according to any one of claims 1 to 8.

11. 1. A short lifespan inhibitor for suppressing short lifespan in mammals, comprising one or more of pyrroloquinoline quinone, imidazopyrroloquinoline quinone and / or salts thereof as an active ingredient.

12. A fatty liver inhibitor for inhibiting fatty liver in mammals, comprising as an active ingredient one or more of pyrroloquinoline quinone, imidazopyrroloquinoline quinone and / or salts thereof.

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