WO2021140640A1 - Index value determination system, mitochondrial activiy evaluation system, index value determination method, and mitochondrial activity evaluation method - Google Patents

Abstract

Provided is an index value determination system that can determine an index value that makes it possible to easily ascertain mitochondrial activity.　The present invention comprises: a concentration value acquisition unit 2 that continuously or discontinuously acquires a concentration value for the acetone released from a subject that has consumed a least one acetone producer that is ultimately degraded in the body to produce acetone selected from among 3-hydroxybutyric acid, 3-hydroxybutyrate, a 3-hydroxybutyrate ester, and acetoacetic acid; and an index value outputting unit 3 that uses at least the acquired acetone concentration value to determine an index value that is correlated with the mitochondrial activity of the subject.

Description

Index value determination system, mitochondrial activity evaluation system, index value determination method and mitochondrial activity evaluation method

The present invention relates to an index value determination system and an index value determination method for determining an index value having a correlation with the mitochondrial activity of a subject, and a mitochondrial activity evaluation system and a mitochondrial activity evaluation method for evaluating mitochondrial activity based on the index value. Regarding.

Mitochondria are important organs that produce energy inside cells, and have the function of converting ingested nutrients into ATP (adenosine triphosphate), which is an energy storage substance. Mitochondrial activity gradually decreases due to aging and the like. Recent studies have revealed that when mitochondrial activity decreases, more active oxygen is generated, which causes aging and various diseases. Therefore, understanding mitochondrial activity contributes to the prevention of aging and lifestyle-related diseases.

Conventionally, as a method for measuring mitochondrial activity, for example, a method for measuring mitochondrial metabolic activity disclosed in Patent Document 1 has been proposed. In this method for measuring the metabolic activity of mitochondria, cells collected from a living body such as a mammal or cultured cells are used, and the cells are permeated with a solution containing streptolysin O to permeate the mitochondria of the permeabilized cells. It is a method for measuring the energy metabolic activity of. According to this method for measuring mitochondrial metabolic activity, the metabolic activity can be measured without damaging the mitochondrial membrane.

Japanese Unexamined Patent Publication No. 2011-205935

Here, from the viewpoint that grasping mitochondrial activity contributes to prevention of aging and lifestyle-related diseases, for example, it can be measured as one of the test items of the health examination, or it is measured by the subject himself on a daily basis. It is important that mitochondrial activity can be easily measured and easily grasped without complicated work.

However, in the method for measuring mitochondrial metabolic activity described in Patent Document 1, since it is necessary to use cells taken out from the body, the measurement work has to be complicated, and mitochondrial activity cannot be easily measured. Therefore, the mitochondrial activity cannot be easily grasped.

The present invention has been made in view of the above circumstances, and is based on an index value determination system and an index value determination method capable of determining an index value that enables easy grasping of mitochondrial activity, and mitochondria based on the index value. An object of the present invention is to provide a mitochondrial activity evaluation system and a mitochondrial activity evaluation method capable of easily evaluating the activity.

Therefore, in order to achieve the above object, the inventor of the present application has conducted extensive research on a method capable of easily grasping mitochondrial activity, and as a result, the correlation between the concentration value of acetone released from the body and mitochondrial activity. Focusing on sex, we found that mitochondrial activity can be grasped by determining an index value that correlates with mitochondrial activity based on the concentration value of acetone, and further, we found that mitochondrial activity can be evaluated using this index value. It was.

That is, when sugar restriction is performed, sugar in the body is insufficient, so fat in the body is decomposed to generate ketone bodies, and these ketone bodies are used to generate energy in mitochondria. Specifically, fatty acids produced by the decomposition of fat are decomposed into 3-hydroxybutyric acid in mitochondria, which is oxidized to acetoacetic acid. Then, acetoacetic acid is taken into the TCA cycle (citric acid cycle) via acetoacetyl CoA and used as energy.

At this time, if the mitochondrial activity is not sufficient to decompose the fat and consume the supplied acetoacetic acid, the consumption of the supplied acetoacetic acid cannot catch up, and the acetoacetic acid is decomposed into acetone and carbon dioxide, and the acetoacetic acid is decomposed from the mitochondria. Acetone released into the body fluid is released with exhaled breath or evaporates from the skin, causing the body to emit an acetone odor.

That is, when the mitochondrial activity is high, the consumption of acetoacetic acid in the body increases, so that the concentration value of acetone released from the body decreases, and conversely, when the mitochondrial activity is low, the consumption of acetoacetic acid decreases. Therefore, the concentration value of acetone released from the body increases. In this way, since there is a correlation between the concentration value of acetone released from the body and mitochondrial activity, by intentionally increasing the amount of ketone bodies in the body, acetone generated from the subject can be obtained. If detected, an index value having a correlation with mitochondrial activity can be determined based on the concentration value of acetone to grasp the mitochondrial activity, and further, the mitochondrial activity can be evaluated based on this index value.

That is, the characteristic configuration of the index value determination system according to the present invention is
Subjects who ingested at least one selected from 3-hydroxybutyric acid, 3-hydroxybutyrate, 3-hydroxybutyric acid ester, and acetoacetic acid, which are acetone-generating species that are finally decomposed in the body to generate acetone. A concentration value acquisition means for continuously or intermittently acquiring the concentration value of the acetone released from
At least the obtained concentration value of acetone is used to provide an index value determining means for determining an index value having a correlation with the mitochondrial activity of the subject.
In addition, the characteristic configuration of the index value determination method for determining the index value having a correlation with the mitochondrial activity of the subject using the index value determination system is as follows.
A concentration value acquisition step of continuously or intermittently acquiring the concentration value of the acetone released from the subject who ingested at least one selected from the acetone-generating species.
At least the obtained concentration value of acetone is used to perform an index value determination step of determining the index value having a correlation with the mitochondrial activity of the subject.
In addition, the characteristic configuration of the index value determination method according to the present invention for achieving the above object is as follows.
Subjects who ingested at least one selected from 3-hydroxybutyric acid, 3-hydroxybutyrate, 3-hydroxybutyric acid ester, and acetoacetic acid, which are acetone-generating species that are finally decomposed in the body to generate acetone. A concentration value acquisition step for continuously or intermittently acquiring the concentration value of the acetone released from
At least the obtained concentration value of acetone is used to perform an index value determination step of determining an index value having a correlation with the mitochondrial activity of the subject.

In the feature configuration according to the index value determination system and the index value determination method according to the present invention, first, the concentration value of acetone released from the subject who ingested at least one selected from the acetone-producing species is continuously calculated. Obtained objectively or intermittently. That is, in the present invention, in order to artificially create a state in which sugar restriction or the like is performed (a state in which fat is decomposed and ketone bodies such as 3-hydroxybutyric acid are supplied) in the body of the subject. At least one selected from 3-hydroxybutyric acid, 3-hydroxybutyrate, 3-hydroxybutyric acid ester, and acetoacetic acid, which are acetone-producing species, is ingested by the subject and released from the subject. I am trying to get the concentration value of acetone.

By doing so, for example, when subjects with different health conditions and sports abilities ingest at least one of the same amount of acetone-producing species, it is acquired according to the mitochondrial activity of each subject. The concentration value of acetone to be obtained changes, and when the same subject ingests at least one of different amounts of acetone-producing species, the concentration value of acetone obtained changes according to the ingestion amount. Will be done.

Then, at least the obtained concentration value of acetone is used to determine an index value that correlates with the mitochondrial activity of the subject.

In this way, the index value having a correlation with the mitochondrial activity can be determined, and the mitochondrial activity of the subject can be easily grasped from this index value without using cells or the like. Then, for this index value, for example, a map is created in advance that defines the relationship between the intake amount of the acetone-producing species, the sex, age, lifestyle, the presence or absence of exercise, the presence or absence of illness, etc. of the subject and the index value. By setting it, detection of lifestyle-related disease prevention group, measurement of aging index, estimation of daily ingestible calories, screening of foods affecting mitochondrial activity and verification of eating habits, various diseases and mitochondrial activity Relationship verification, relationship verification between longevity and mitochondrial activity, effect verification of exercise training and setting of optimal training amount, confirmation of mental stress based on short-term decrease in mitochondrial activity, balance measurement of glycolytic system and TCA cycle, mitochondria It can also be used to grasp the state of illness.

For example, when there is a correlation between oxidative stress-related diseases and mitochondrial dysfunction, the index values that correlate with mitochondrial activity can be used to control diabetes and develop diabetic nephropathy (DKG). It is possible to predict the onset, severity, complications, etc. of diseases such as risk evaluation and risk evaluation of patients who develop chronic obstructive pulmonary disease (COPD). In addition, if mitochondrial dysfunction is observed before the onset of oxidative stress-related diseases, an index value that correlates with mitochondrial activity can be a biomarker. The decision makes it possible to predict the onset of oxidative stress-related diseases. In addition, if foods or exercises claiming to increase mitochondrial activity were advocated, the subject ingested such foods or performed such exercises. By determining the index value based on the state, it is possible to evaluate the effect of food or exercise therapy (the effect of increasing mitochondrial activity) using the index value.

As described above, according to the index value determination system and the index value determination method according to the present invention, the concentration value of acetone released from the subject is acquired, and the mitochondrial activity is based on the acquired concentration value of acetone. Since it is possible to determine an index value that correlates with, the mitochondrial activity can be easily grasped from the determined index value without requiring complicated measurement work as compared with the conventional measurement method that requires cells or the like. be able to.

Further, a further characteristic configuration of the index value determination system according to the present invention is that the concentration value acquisition means acquires a reference concentration value of acetone released from a subject who has not ingested the acetone-producing species.
In the index value determining means, the rate of increase in acetone concentration in a predetermined section from the reference concentration value to the maximum concentration value of the acetone is determined as the index value.
A further characteristic configuration of the index value determining method according to the present invention is to acquire a reference concentration value of acetone released from a subject who has not ingested the acetone-generating species in the concentration value acquisition step.
In the index value determination step, the rate of increase in acetone concentration in a predetermined section from the reference concentration value to the maximum concentration value of the acetone concentration value is determined as the index value.

In each of the above feature configurations, the rate of increase in acetone concentration is determined as an index value. When a subject ingests a certain amount of acetone-producing species, the concentration value of acetone released from the subject increases as the blood concentration of the acetone-generating species increases, but the higher the mitochondrial activity, the higher the concentration. Since the amount of acetoacetic acid processed increases, the generation of acetone due to the decomposition of acetoacetic acid is suppressed. That is, the higher the mitochondrial activity, the lower the rate of increase in acetone concentration. Therefore, the mitochondrial activity can be grasped by using the rate of increase in acetone concentration as an index value.

Further, a further characteristic configuration of the index value determining system according to the present invention is that the index value determining means maintains the concentration value within a predetermined range for a certain period of time after the concentration value of acetone reaches the maximum concentration value. The point is that the minimum intake of the acetone-generating species is determined as the index value.
A further characteristic configuration of the index value determining method according to the present invention is to maintain the concentration value within a predetermined range for a certain period of time after the concentration value of acetone reaches the maximum concentration value in the index value determining step. The point is that the minimum intake of the acetone-generating species is determined as the index value.

In each of the above characteristic configurations, after the concentration value of acetone reaches the maximum concentration value, the minimum intake amount of the acetone-generating species that maintains the concentration value within a predetermined range for a certain period of time is determined as the index value. I have to. According to the findings of the present inventors, if the intake of acetone-producing species ingested by the subject does not exceed the amount that mitochondria can process, the concentration value of acetone decreases after reaching the maximum value. On the other hand, when the amount of acetone exceeds the amount that can be processed by mitochondria, the concentration value of acetone reaches the maximum value and then maintains the concentration value within a predetermined range for a certain period of time. Therefore, the higher the mitochondrial activity, the higher the minimum intake of acetone-producing species, which keeps the concentration value within a predetermined range for a certain period of time after the concentration value of acetone reaches the maximum concentration value. Therefore, the mitochondrial activity can be grasped by using the minimum intake of the acetone-generating species as an index value as described above.

Further, a further characteristic configuration of the index value determination system according to the present invention is that the subject who ingests at least one selected from the acetone-producing species ingests nutrients together with the acetone-generating species. There is a point.
A further characteristic configuration of the index value determining method according to the present invention is that the subject who ingests at least one selected from the acetone-producing species ingests nutrients together with the acetone-producing species. It is in.

According to the newly discovered findings by the inventors of the present application, the obtained acetone concentration value is obtained when the subject is ingesting nutrients together with the acetone-producing species, as compared with the case where the subject is ingesting only the acetone-producing species. The reliability of the device is improved, and the measurement can be performed with good reproducibility. This is presumed to be due to the following reasons.

That is, when the subject is hungry at the time of measurement, or when insulin is excessively secreted due to eating a high-sugar diet, the subject falls into a hypoglycemic state. May be present. When the subject is in a hypoglycemic state, the ingested acetone-generating species is used to generate energy, and the amount of acetone-generating species used to generate energy fluctuates during measurement, resulting in acetone. Since the amount of energy generated also fluctuates accordingly, the obtained acetone concentration value may fluctuate according to the amount of energy generated. However, when nutrients are ingested together with acetone-generating species, the blood glucose level rises due to the intake of nutrients, and the generation of energy using the acetone-generating species is suppressed. Therefore, the acetone-generating species used for energy generation It is presumed that this is because the acetone concentration value can be obtained in a state where the amount is less likely to fluctuate during measurement.

According to each of the above characteristic configurations, since the subject is ingesting nutrients together with the acetone-producing species, the subject is hungry at the time of measurement, or insulin is excessively secreted, resulting in hypoglycemia. Even in the state, it is possible to suppress the generation of energy using the ingested acetone-generating species, and the acetone concentration in a state where the fluctuation in the amount of acetone-generating species during measurement due to the energy generation is suppressed. Since the value can be obtained, the reliability of the acquired acetone concentration value is improved, and the measurement can be performed with good reproducibility.

In addition, the characteristic configuration of the mitochondrial activity evaluation system according to the present invention is
With any of the above index value determination systems,
An activity evaluation means for evaluating the mitochondrial activity of the subject based on the determined index value is provided.
In the activity evaluation means, the determined index value is compared with the past index value for the same subject, and the mitochondrial activity of the subject is evaluated.
In addition, the characteristic configuration of the mitochondrial activity evaluation method for evaluating the mitochondrial activity of the subject using the mitochondrial activity evaluation system is as follows.
A concentration value acquisition step of continuously or intermittently acquiring the concentration value of the acetone released from the subject who ingested at least one selected from the acetone-generating species.
An index value determination step for determining the index value having a correlation with the mitochondrial activity of the subject using at least the obtained concentration value of acetone.
Based on the determined index value, an activity evaluation step for evaluating the mitochondrial activity of the subject is performed.
In the activity evaluation step, the determined index value is compared with the past index value for the same subject to evaluate the mitochondrial activity of the subject.
In addition, the characteristic configuration of the mitochondrial activity evaluation method according to the present invention is
After determining the index value by any of the above index value determination methods
Based on the determined index value, an activity evaluation step for evaluating the mitochondrial activity of the subject is executed.
In the activity evaluation step, the determined index value is compared with the past index value for the same subject to evaluate the mitochondrial activity of the subject.

In the feature configuration of the mitochondrial activity evaluation system and the mitochondrial activity evaluation method according to the present invention, first, the concentration value of acetone released from the subject who ingested at least one selected from the acetone-producing species is continuously calculated. Obtained objectively or intermittently. Then, at least the obtained concentration value of acetone is used to determine an index value that correlates with the mitochondrial activity of the subject. Then, this index value is compared with the past index value for the same subject to evaluate the mitochondrial activity of the subject. In this way, by comparing the acquired index value with the past index value for the same subject, the change in the mitochondrial activity of the subject, that is, the current mitochondrial activity is higher than that of the past mitochondrial activity. It is possible to evaluate whether it is low or low. By making it possible to evaluate mitochondria, it is possible to detect lifestyle disease prevention groups, measure aging indicators, estimate the calories that can be consumed in a day, screen foods that affect mitochondrial activity, and verify eating habits. , Verification of the relationship between various diseases and mitochondrial activity, Verification of the relationship between longevity and mitochondrial activity, verification of the effect of exercise training and setting of the optimum training amount, confirmation of mental stress based on short-term decrease in mitochondrial activity, and glycolytic system It is possible to measure the balance of the TCA cycle and grasp the state of mitochondrial disease.

For example, when there is a correlation between oxidative stress-related diseases and mitochondrial dysfunction, evaluation of mitochondria can be used to control diabetes, evaluate the risk of developing diabetic nephropathy (DKG), and chronically. It enables useful evaluation for predicting the onset, severity, complications, etc. of diseases such as risk evaluation of patients who develop obstructive pulmonary disease (COPD). In addition, if mitochondrial dysfunction is observed before the onset of oxidative stress-related diseases, evaluation of mitochondria can be a biomarker. The onset of oxidative stress-related diseases can be predicted. In addition, if foods or exercises that claim to increase mitochondrial activity are advocated, mitochondrial activity in subjects who have ingested such foods or performed such exercises. By evaluating, it is also possible to evaluate the effect of food and exercise therapy (the effect of increasing mitochondrial activity).

It is a block diagram which showed the schematic structure of the index value determination device and the mitochondrial activity evaluation device which concerns on this embodiment. It is a flowchart which shows the index value determination method and mitochondria activity evaluation method which concerns on this Embodiment. It is a graph which shows the relationship between the elapsed time after ingesting an acetone-producing species, the amount of increase in blood 3HB concentration, and the amount of increase in acetone concentration. It is a graph which shows the relationship between the elapsed time after ingesting an acetone-producing species, the amount of increase in blood 3HB concentration, and the amount of increase in acetone concentration. It is a graph which shows the relationship between the elapsed time after ingesting an acetone-producing species, the amount of increase in blood 3HB concentration, and the amount of increase in acetone concentration. It is a graph which shows the relationship between the elapsed time after ingesting an acetone-producing species, the amount of increase in blood 3HB concentration, and the amount of increase in acetone concentration. It is a graph which shows the relationship between the elapsed time after ingesting an acetone-generating species, and the amount of change of an acetone concentration. It is a graph which shows the relationship between the elapsed time after ingestion of an acetone generating species and sugar, and the amount of change of an acetone concentration. It is a graph which shows the relationship between the elapsed time after ingesting an acetone-generating species, and the acetone concentration. It is a graph which shows the area under each line graph in FIG. It is a graph which shows the relationship between the elapsed time after ingesting an acetone-generating species, and the acetone concentration. It is a graph which shows the area under each line graph in FIG.

[First Embodiment]
Hereinafter, the index value determining device and the mitochondrial activity evaluation device according to the first embodiment will be described with reference to the drawings.

As shown in FIG. 1, the mitochondrial activity evaluation device 1 according to the present embodiment acquires a concentration value acquisition unit 2 (concentration value acquisition means) for acquiring an acetone concentration value and a concentration value acquired by the concentration value acquisition unit 2. Based on the index value output unit 3 (index value determination means) that determines and outputs the index value that correlates with the mitochondrial activity of the subject and the index value output from the index value output unit 3, the subject is subject to use. It includes an activity evaluation unit 5 (activity evaluation means) for evaluating the mitochondrial activity of the examiner and an index value storage unit 6 for storing the index value, and the concentration value acquisition unit 2 and the index value output unit 3 are index values. The determination device 4.

The concentration value acquisition unit 2 acquires the concentration value of acetone from the exhalation sensor 10 that detects acetone contained in the exhaled breath of the subject, and transmits the acquired concentration value to the index value output unit 3. The detection result from the exhaled breath sensor 10 is transmitted to the concentration value acquisition unit 2 by wireless communication or wired communication.

The index value output unit 3 determines the rate of increase in acetone concentration as an index value based on the concentration value received from the index value output unit 3, and transmits it to the activity evaluation unit 5 or a display device 11 provided as appropriate. Specifically, in the present embodiment, it is selected from 3-hydroxybutyric acid, 3-hydroxybutyrate, 3-hydroxybutyric acid ester, and acetoacetic acid, which are acetone-generating species that are finally decomposed in the body to generate acetone. The concentration value of acetone contained in the exhaled breath of the subject who ingested at least one of them, and the concentration value of acetone contained in the exhaled breath of the subject who did not ingest the species that generated acetone (reference concentration value). Based on the above, the rate of increase in acetone concentration in a predetermined section from the reference concentration value to the maximum concentration value of acetone is determined as an index value. When the rate of increase in acetone concentration is used as an index value, the higher the mitochondrial activity, the lower the rate of increase in acetone concentration. The display device 11 may be incorporated in the mitochondrial activity evaluation device 1 or the index value determination device 4, or may be separately provided outside these devices.

The activity evaluation unit 5 determines whether or not the rate of increase in acetone concentration received from the index value output unit 3 is equal to or higher than the predetermined speed, and if it is not higher than the predetermined speed, the activity evaluation unit 5 displays a signal for displaying that fact. Send to. On the other hand, when the rate of increase in acetone concentration is equal to or higher than a predetermined rate, the received rate of increase in acetone concentration is transmitted to the index value storage unit 6 for storage, and the index value storage unit 6 stores the past acetone of the same subject. Check whether the concentration increase rate is memorized, and if it is memorized, compare the received acetone concentration increase rate with the past acetone concentration increase rate for the same subject, and the mitochondrial activity is increased. It evaluates whether it is decreasing or increasing, and transmits the result to the display device 11.

Next, the index value determination method and the mitochondrial activity evaluation method will be described with reference to FIG. First, the reference concentration value is measured in step # 1. Specifically, the breath sensor 10 is used to detect acetone contained in the breath of a subject who has not ingested the acetone-generating species, and obtains an acetone concentration value (reference concentration value). When the mitochondrial activity evaluation device 1 is used, the detection result by the exhaled breath sensor 10 is transmitted to the concentration value acquisition unit 2 to acquire the reference concentration value of acetone, and this reference concentration value is the index value output unit 3. Will be sent to.

Then, in step # 2, the subject ingests the acetone-producing species. The amount of acetone-generating species ingested by the subject shall be an appropriate amount determined for each subject according to the health condition, sports ability, etc., and the rate of increase in acetone concentration shall be equal to or higher than the predetermined rate in step # 6 described later. In the case of the same subject, the same amount of acetone-producing species is ingested in the index value determination method and the mitochondrial activity evaluation method to be performed in the future. The intake of the acetone-generating species is preferably 0.5 g to 50 g, more preferably 1 g to 25 g, and most preferably 3 g to 10 g.

After that, in step # 3, the concentration value of acetone is measured at regular intervals (concentration value acquisition step). That is, the acetone contained in the exhaled breath of the subject in the state of ingesting the acetone-generating species is detected by using the exhaled breath sensor 10 at regular intervals, and the concentration value of acetone is acquired. When the mitochondrial activity evaluation device 1 is used, the detection result by the exhaled breath sensor 10 is transmitted to the concentration value acquisition unit 2 to acquire the concentration value of acetone, and this concentration value is transmitted to the index value output unit 3. Will be done.

Next, in step # 4, it is determined whether or not the maximum concentration value of acetone has been acquired, and if the maximum concentration value has been acquired, the process proceeds to step # 5, and if the maximum concentration value has not been acquired. Return to step # 3. Specifically, if the acquired concentration value is higher than the concentration value measured and acquired at the timing immediately before the measurement of this concentration value, it is judged that the maximum concentration value has not been acquired, and if it is lower. It is judged that the maximum concentration value has been obtained. When the mitochondrial activity evaluation device 1 is used, the index value output unit 3 determines whether or not the maximum concentration value of acetone has been acquired.

As step # 5, the rate of increase in acetone concentration as an index value is determined (index value determination step). Specifically, the concentration value of acetone is used as a reference based on the concentration value and elapsed time at a predetermined timing from the reference concentration value to the maximum concentration value and the reference concentration value. The rate of increase in acetone concentration from the concentration value to the concentration value at a predetermined timing is determined as an index value. When the mitochondrial activity evaluation device 1 is used, the index value output unit 3 calculates the acetone concentration increase rate, the acetone concentration increase rate is determined as an index value, and the determined acetone concentration increase rate is the activity evaluation unit. It is transmitted to 5 or is transmitted to the display device 11. The predetermined timing is, for example, the timing at which the rate of increase in acetone concentration becomes constant, and when the mitochondrial activity evaluation device 1 is used, it is an index based on the measurement data that the rate of increase in acetone concentration becomes constant. This is the timing determined by the value output unit 3. The rate of increase in acetone concentration as an index value may be calculated based on the reference concentration value and the maximum concentration value, and the time required to reach the maximum concentration value from the reference concentration value.

These steps # 1 to # 5 correspond to the index value determination method, and by performing steps # 1 to # 5 as described above, the acetone concentration as an index value having a correlation with mitochondrial activity. Since the rate of increase can be determined, the mitochondrial activity of the subject can be easily grasped from this index value without using cells or the like. Then, the index value determined in this way defines, for example, the relationship between the intake amount of the acetone-producing species, the sex of the subject, the age, the lifestyle, the presence or absence of exercise, the presence or absence of illness, and the index value in advance. By creating a map, you can detect lifestyle-related disease prevention groups, measure aging indicators, estimate the calories you can consume in a day, screen foods that affect mitochondrial activity, verify your eating habits, and check various diseases. Verification of the relationship between mitochondrial activity and longevity, verification of the effect of exercise training and setting of optimal training amount, confirmation of mental stress based on short-term decrease in mitochondrial activity, glycolytic system and TCA cycle It can also be used for balance measurement and grasping the state of mitochondrial diseases.

In step # 6, it is determined whether or not the determined rate of increase in acetone concentration is equal to or higher than the predetermined rate, and if it is determined that the rate is equal to or higher than the predetermined rate, the process proceeds to step # 7. On the other hand, if it is determined that the speed is lower than the predetermined speed, the process returns to step # 2, the intake of the acetone-producing species is increased, and the process proceeds to step # 3 again. It is possible that the rate of increase in acetone concentration did not sufficiently correlate with the mitochondrial activity of the subject because the intake of the acetone-producing species ingested by the subject was sufficient for the mitochondria to process. Is high.

In step # 7, it is determined whether or not there is a past rate of increase in acetone concentration for the same subject, and if it exists, the process proceeds to step # 8, and if it does not exist, the process ends. Then, in step # 8, the rate of increase in acetone concentration determined this time is compared with the rate of increase in acetone concentration in the past for the same subject, and is the mitochondrial activity of the subject higher than in the past? Alternatively, it is evaluated whether it is low (activity evaluation step).

When the mitochondrial activity evaluation device 1 is used for these steps # 6 to # 8, the activity evaluation unit 5 stores the determined acetone concentration increase rate in the index value storage unit 6, and the acetone concentration increase rate. Is determined to be above the predetermined speed (step # 6), and if it is determined to be above the predetermined speed, the past acetone concentration for the same subject is referred to with reference to the index value storage unit 6. It is determined whether the rate of increase is memorized (step # 7), and if it is memorized, the rate of increase in the acetone concentration is compared with the rate of increase in the past acetone concentration for the same subject, and the test is performed. It is evaluated whether the mitochondrial activity of the person is higher or lower than in the past, and the result is transmitted to the display device 11. On the other hand, if it is determined that the past rate of increase in acetone concentration for the same subject is not memorized, the process ends.

In this way, by using the rate of increase in acetone concentration as an index value of mitochondrial activity, it is possible to evaluate whether the mitochondrial activity of the same subject is higher or lower than the past results. For example, if the rate of increase in acetone concentration is determined as an index value for each subject in regular health examinations, how the mitochondrial activity has changed compared to the rate of increase in acetone concentration in the past can be seen. The subject can know.

As described above, according to the index value determining method according to the present embodiment, the rate of increase in acetone concentration, which is an index value having a correlation with the mitochondrial activity of the subject, can be determined, and the rate of increase in acetone concentration can be used. Various tests and verifications related to mitochondrial activity can be performed. In addition, by comparing the rate of increase in acetone concentration, which is an index value, with the rate of increase in acetone concentration in the past of the same subject, it is possible to inform the subject of how the mitochondrial activity has changed, and it is possible to inform the subject of lifestyle-related diseases. It can give an opportunity to work on prevention of aging and prevention of aging.

Hereinafter, specific Experimental Examples 1 to 4 will be described.

(Experimental Example 1)
When 1 g of 3-hydroxybutyrate (3HB salt) (10 ml of 10% 3HB neutralized with Na: Ca: Mg = 70: 15: 15) was ingested, 0 minutes (before ingestion), 30 minutes, FIG. 3 shows the relationship between the increase in blood 3HB concentration (increase with respect to 0 minutes) and the increase in acetone concentration in exhaled breath (increase with respect to 0 minutes) after 60 minutes, 90 minutes, and 120 minutes. The acetone concentration value in the exhaled breath was analyzed by gas chromatography after collecting 1 L of the exhaled breath in a collection bag every hour. Since the amount of 3HB salt ingested was small compared to the mitochondrial activity of subject A (52-year-old man), the increase in blood 3HB concentration increased to 0.2 mM after 30 minutes and then decreased to 0 during exhalation. The amount of increase in the acetone concentration in the above also decreased immediately after reaching the maximum value at a low value of 0.1 ppm after 60 minutes. If the change pattern of the increase in the concentration value of acetone becomes a pattern that decreases immediately after the increase is maximized, it is judged that it is necessary to increase the intake of 3HB salt and perform remeasurement. ..
Since the rate of increase in acetone concentration per hour from 0 minutes to 60 minutes (0.096 ppm / hr) is lower than the rate of increase in acetone concentration in Experimental Examples 2 to 4 described later, this rate of increase in acetone concentration. It can also be determined that if is slower than the predetermined rate (eg 0.1 ppm / hr), it is necessary to increase the amount of 3HB salt ingested and perform remeasurement.
In addition, the peak of the increase in the concentration of acetone in the exhaled breath appears later than the peak of the increase in the concentration of 3HB in the blood until the acetone generated in the mitochondria is transferred to the body fluid and further released from the exhaled breath. It is thought that this is because it takes time.
In addition, when the total amount of 3HB salt ingested was transferred to body fluid from the amount of water in the body (64 kg × 70% = 45 L) estimated from the body weight (64 kg) of subject A and the intake of 3HB salt (1 g). The blood 3HB concentration is 1 g / 104 (3 HB molecular weight) / 45 L = 0.21 mM, which is almost the same as the measured value of 0.2 mM. It is presumed that it was used for.

(Experimental Example 2)
When 3 g of 3HB salt (30 ml of 10% 3HB neutralized with Na: Ca: Mg = 70: 15: 15) was ingested, 0 minutes (before ingestion), 30 minutes, 60 minutes, 90 minutes, 120 minutes. FIG. 4 shows the relationship between the increase in blood 3HB concentration (increase with respect to 0 minutes) and the increase in acetone concentration in exhaled breath (increase with respect to 0 minutes) after minutes. The acetone concentration value in the exhaled breath was analyzed by gas chromatography after collecting 1 L of the exhaled breath in a collection bag at each time. Since the amount of 3HB salt ingested was sufficiently large for the mitochondrial activity of subject A (52-year-old man), the increase in blood 3HB concentration increased to 0.4 mM after 60 minutes and was then used in mitochondria. It gradually decreased. The amount of increase in the concentration of acetone in the exhaled breath increased to 0.9 ppm after 60 minutes, and then gradually decreased while maintaining the predetermined range. If the change pattern of the amount of increase in the concentration value of acetone becomes a pattern that maintains within the predetermined range after the amount of increase is maximized, it is judged that the measurement is normal and there is no need to perform remeasurement. It shall be.
In this case, the index value having a correlation with the mitochondrial activity may be an intake amount (3 g in this experimental example) that keeps within a predetermined range after the increase amount of the acetone concentration value reaches the maximum. However, the rate of increase in acetone concentration per hour from 0 minutes to 60 minutes may be set (0.798 ppm / hr). The latter is a simpler and more detailed index.

(Experimental Example 3)
When 5 g of 3HB salt (50 ml of 10% 3HB neutralized with Na: Ca: Mg = 70: 15: 15) was ingested, 0 minutes (before ingestion), 30 minutes, 60 minutes, 90 minutes, 120 minutes. FIG. 5 shows the relationship between the increase in blood 3HB concentration (increase with respect to 0 minutes) and the increase in acetone concentration in exhaled breath (increase with respect to 0 minutes) after minutes. The acetone concentration value in the exhaled breath was analyzed by gas chromatography after collecting 1 L of the exhaled breath in a collection bag every hour. Since the amount of 3HB salt ingested was sufficiently large for the mitochondrial activity of subject A (52-year-old man), the increase in blood 3HB concentration increased to 0.7 mM after 60 minutes and was then used in mitochondria. It gradually decreased. Although the intake of 3HB salt is 5 times that of 1 g of Experimental Example 1, the increase in the maximum 3HB concentration is 3.5 times, which means that it is not possible to consume all of the ingested 3HB. It is thought that this is the reason. The amount of increase in acetone concentration in exhaled breath increased to 1.1 ppm after 90 minutes and then gradually decreased. Since the pattern of change in the amount of increase in the concentration value of acetone is a pattern in which the amount of increase is maintained within a predetermined range after the amount of increase is maximized, the measurement can be performed normally as in the case of Experimental Example 2 above. , Judge that there is no need to remeasure.
The rate of increase in acetone concentration (0.756 ppm / hr) per hour from 0 minutes to 60 minutes as an index value was almost the same value as in Experimental Example 2. From this, the amount of 3HB salt ingested by the subject is higher than the amount of intake such that the pattern of increase in the concentration value of acetone becomes a pattern of maintaining within a predetermined range after the increase is maximized. There is no particular problem at most. Further, by continuously performing the measurement using a sensor element or the like capable of detecting acetone, the rate of increase in acetone concentration as an index value can be calculated more accurately.

(Experimental Example 4)
When 3 g of 3HB salt (30 ml of 10% 3HB neutralized with Na: Ca: Mg = 70: 15: 15) was ingested, 0 minutes (before ingestion), 30 minutes, 60 minutes, and 90 minutes later. The relationship between the increase in blood 3HB concentration (increase with respect to 0 minutes) and the increase in acetone concentration in exhaled breath (increase with respect to 0 minutes) is shown in FIG. The concentration of acetone in the exhaled breath was analyzed by gas chromatography after collecting 1 L of exhaled breath in a collection bag every hour. Since the amount of 3HB ingested was sufficiently large for the mitochondrial activity of subject B (59-year-old man), the amount of increase in blood 3HB concentration increased to 0.7 mM after 60 minutes and was used by mitochondria and gradually decreased. did. The amount of increase in acetone concentration in exhaled breath increased to 0.8 ppm after 30 minutes and then gradually decreased. If the pattern of increase in the concentration of acetone becomes like this, the measurement is judged to be successful. The rate of increase in acetone concentration per hour (1.602 ppm / hr) from 0 to 30 minutes as mitochondrial activity was almost twice as high as that of Subject A in Experimental Examples 2 and 3. It is probable that the subject B was older and had lower mitochondrial activity, so that the rate of use of acetoacetic acid by mitochondria was slower, and the rate of acetone concentration increased because more acetone was generated.

[Second Embodiment]
In the second embodiment, a subject ingesting at least one selected from 3-hydroxybutyric acid, 3-hydroxybutyrate, 3-hydroxybutyric acid ester, and acetoacetic acid, which are acetone-generating species, generates acetone. It differs from the first embodiment in that it is ingesting nutrients at the same time as the seeds.

That is, in the second embodiment, the mitochondrial activity evaluation device 1 is in a state where the concentration value of acetone contained in the exhaled breath of the subject who has ingested the nutrients at the same time as the acetone-generating species and the acetone-generating species and the nutrients have not been ingested. Based on the concentration of acetone contained in the exhaled breath of the subject (reference concentration value), the rate of increase in acetone concentration is determined as an index value, and the subject is based on the rate of increase in acetone concentration, which is the determined index value. To assess the mitochondrial activity of. The "nutrient" in the present application is not particularly limited as long as it is converted into glucose in the body, and examples thereof include sugars, carbohydrates, proteins, amino acids, lipids, and dietary fiber. , The subject may ingest only one of these together with the glucose-producing species, or may ingest a plurality of them in combination.

In this way, when the subject is ingesting nutrients at the same time as the acetone-producing species, the subject is hungry at the time of measurement, or insulin is excessively secreted, resulting in hypoglycemia. Even in the state, it is possible to suppress the generation of energy using the ingested acetone-generating species, and the acetone concentration in a state where the fluctuation in the amount of acetone-generating species during measurement due to the energy generation is suppressed. Since the value can be obtained, the reliability of the acquired acetone concentration value is improved, the measurement can be performed with good reproducibility, and the evaluation accuracy of the mitochondrial activity can be improved.

Below, we will explain the experiments conducted to confirm the effect of ingesting nutrients at the same time as the acetone-generating species.

A sample in which 5 g of 3HB was dissolved in 100 ml of water and adjusted to pH 4 with potassium hydroxide (Sample 1) and a sample in which 5 g of 3HB and 2 g of sugar were dissolved in 100 ml of water and adjusted to pH 4 with potassium hydroxide (Sample 1). 2) is prepared and the subject C is ingested of these samples 1 and 2, respectively, and the exhaled breath of the subject C in a resting state before the sample is ingested and every predetermined time elapses from the sample ingestion. Was collected and analyzed by gas chromatography to measure the concentration of acetone in the exhaled breath. FIG. 7 is a graph showing the relationship between the elapsed time after ingestion of the sample and the amount of change in the acetone concentration value (the amount of change with respect to the amount before ingestion) in the case of ingesting sample 1, and FIG. 8 shows the ingestion of sample 2. It is a graph which shows the relationship between the elapsed time after ingestion of a sample, and the amount of change (change amount with respect to before ingestion) of an acetone concentration value about a case. In addition, two experiments in which sample 1 was ingested in the morning (“1 am” and “2 am” in FIG. 7) and two experiments in which sample 1 was ingested in the afternoon (“1 pm” in FIG. 7). "2 pm"), 2 experiments ingesting sample 2 in the morning ("am + nutrition 1", "am + nutrition 2" in FIG. 8), 2 experiments ingesting sample 2 in the afternoon (Fig. 8) A total of eight experiments (“afternoon + nutrition 1” and “afternoon + nutrition 2”) in 8 were performed on different days.

Comparing the graphs related to each experiment with respect to the case of ingesting sample 1, it can be seen that there is a large variation as shown in FIG. Specifically, the minimum and maximum values of the amount of change in the acetone concentration value after the lapse of a predetermined time from the intake of sample 1 are -119 ppb (2 pm) and the maximum value of 31 ppb (2 pm) after 15 minutes. 1) am, the minimum value is -37 ppb (2 am) after 30 minutes, the maximum value is 26 ppb (1 am), and the minimum value is -35 ppb (1 pm) after 45 minutes. The maximum value was 223 ppb (2 am), and after 60 minutes, the minimum value was 93 ppb (1 am) and the maximum value was 287 ppb (2 am).

On the other hand, when comparing the graphs related to each experiment with respect to the case of ingesting sample 2, it can be seen that the variation is smaller than that of the case of ingesting sample 1, as shown in FIG. Specifically, the minimum and maximum values of the change in the acetone concentration value after the lapse of a predetermined time from the intake of sample 2 are 19 ppb (morning + nutrition 1) at the minimum value and 75 ppb at the maximum value at the lapse of 15 minutes. (Afternoon + Nutrition 2), the minimum value is 86 ppb (AM + Nutrition 1) after 30 minutes, the maximum value is 196 ppb (Afternoon + Nutrition 2), and the minimum value is 45 minutes. 234 ppb (morning + nutrition 1), maximum value 302 ppb (morning + nutrition 2), minimum value is 355 ppb (afternoon + nutrition 2), maximum value is 539 ppb (morning + nutrition 2) after 60 minutes. there were.

In this way, the reason why the degree of variation changes between the case where sugar is ingested at the same time as 3HB and the case where sugar is not ingested is that when sugar is not ingested at the same time as 3HB, the subject C at the time of measurement. Is hungry, or is in a state of excessive insulin secretion due to eating a sugar-rich diet, resulting in a hypoglycemic state, and the ingested 3HB is used to generate energy, and energy When the amount of 3HB used for production fluctuates during measurement, the amount of acetone generated also fluctuates accordingly, and as a result, the obtained acetone concentration value fluctuates according to the amount of energy produced. However, when sugar is ingested at the same time as 3HB, the blood sugar level rises due to the intake of sugar, and the generation of energy using 3HB is suppressed. It is presumed that the acetone concentration value can be obtained in a state where the amount is less likely to fluctuate during measurement, and the variation is small.

Next, we will explain an experiment conducted using rats to verify the relationship between mitochondrial activity and the concentration of acetone released from the body.

A 10% 3HB sodium solution (acetone-generating species) was administered to two rats (rat A, rat B) so as to weigh 1 g per kg of body weight, and the acetone released from the tail between 115 and 125 minutes after administration. The concentration was measured with a semiconductor gas sensor. Next, 10 mg / ml streptozotocin (STZ) was intraperitoneally administered to the same two rats A and B so as to be 50 mg / kg body weight, and the rats were bred for 2 weeks, and then a 10% 3HB sodium solution was added to 1 kg body weight. The dose was 1 g per dose, and the concentration of acetone released from the tail was measured with a semiconductor gas sensor between 115 and 125 minutes after the administration. 9 and 10 show the results for rat A, FIGS. 11 and 12 show the results for rat B, respectively, and FIGS. 9 and 11 show the 3HB sodium solution before and after STZ administration for each mouse. It is a graph which shows the relationship between the elapsed time after ingesting, and the acetone concentration. In addition, FIGS. 10 and 12 show the area (that is, the amount of acetone (μg)) under each line graph (before STZ administration and after STZ administration) from 0 minutes to 115 minutes in FIGS. 9 and 11, respectively. It is a graph.

It has been reported that streptozotocin has the effect of lowering mitochondrial activity by lowering mitochondrial membrane potential and enzyme activity and inhibiting ATP synthesis (Int. J. Mol. Sci. 2012, 13, 5751-5767). As is clear from FIGS. 9 and 11, the concentration of acetone released before STZ administration gradually decreased in both rats before and after STZ administration, but STZ. After administration (ie, reduced mitochondrial activity), high concentrations of acetone continued to be released. Further, as shown in FIGS. 10 and 12, the amount of acetone released in 115 minutes in both rats was about twice as high after STZ administration as compared with before STZ administration.

From these facts, it was experimentally confirmed that the lower the mitochondrial activity, the easier it is for acetone to be released from the body, and there is a high correlation between the mitochondrial activity and the acetone concentration value. In addition, since acetone is released from the body by ingesting 3HB, it has a correlation with mitochondrial activity by administering 3HB to the subject and then measuring the concentration of acetone released from the subject. It was also confirmed that the index value could be determined and the mitochondrial activity of the subject could be evaluated based on the determined index value.

[Another Embodiment]
[1] In the above embodiment, an embodiment in which the rate of increase in acetone concentration is used as an index value is shown, but the present invention is not limited to this. As an index value that correlates with mitochondrial activity, instead of the rate of increase in acetone concentration, an acetone-generating species that maintains the concentration value within a predetermined range for a certain period of time after the concentration value of acetone reaches the maximum concentration value. The minimum intake of may be used. The above-mentioned fixed time is 5 to 30 minutes, preferably 5 to 10 minutes, and the above-mentioned predetermined range is ± 30% of the maximum concentration value, preferably ± 20% of the maximum concentration value. .. If the intake of the acetone-producing species ingested by the subject does not exceed the amount that can be processed by mitochondria, the concentration value of acetone reaches the maximum value and then decreases, whereas the mitochondria can process it. If the amount is exceeded, the concentration value of acetone reaches the maximum value and then maintains the concentration value within a predetermined range for a certain period of time. Therefore, the higher the mitochondrial activity, the higher the minimum intake of acetone-producing species, which keeps the concentration value within a predetermined range for a certain period of time after the concentration value of acetone reaches the maximum concentration value. Therefore, the mitochondrial activity can be grasped even when the minimum intake of the acetone-producing species as described above is used as an index value.

[2] In the above embodiment, acetone contained in the exhaled breath of the subject is detected at regular intervals, that is, intermittently by using the exhaled breath sensor, but the present invention is not limited to this, and is not limited to this. Acetone may be continuously detected continuously. Further, the sensor for detecting acetone is not limited to the exhalation sensor, and a skin sensor capable of detecting acetone released from the skin of the subject can be used.

[3] In the above embodiment, an embodiment in which the index value is transmitted from the activity evaluation unit 5 to the index value storage unit 6 and stored is illustrated, but the present invention is not limited to this, and the index value output unit stores the index value. The index value may be transmitted and stored in the unit, or a storage unit may be provided as appropriate for storing the concentration value acquired by the concentration value acquisition unit.

[4] In the above embodiment, the index value output unit 3 determines and outputs the rate of increase in the acetone concentration as the index value, but it is not always necessary to output the index value and the index value is stored. However, the activity evaluation unit may access and acquire the information as appropriate.

[5] The above-mentioned mitochondrial activity evaluation method and index value determination method can be executed without using the mitochondrial activity evaluation device and the index value determination device.

[6] In the second embodiment, the present subject is ingesting nutrients at the same time as the acetone-generating species, but the present invention is not limited to this, and the subject is not limited to this, and is before ingesting the acetone-generating species or acetone. Nutrients may be ingested after ingesting the outbreak.

An index value determination system and an index value determination method capable of determining an index value that enables easy grasping of mitochondrial activity, and a mitochondrial activity evaluation system and an index value determination method that can easily evaluate mitochondrial activity based on the index value. It can be used as a method for evaluating mitochondrial activity.

1 Mitochondrial activity evaluation device (mitochondrial activity evaluation system)
2 Concentration value acquisition unit (concentration value acquisition means)
3 Index value output unit (index value determination means)
4 Index value determination device (index value determination system)
5 Activity evaluation department (activity evaluation means)

Claims (12)

1. Subjects who ingested at least one selected from 3-hydroxybutyric acid, 3-hydroxybutyrate, 3-hydroxybutyric acid ester, and acetoacetic acid, which are acetone-generating species that are finally decomposed in the body to generate acetone. A concentration value acquisition means for continuously or intermittently acquiring the concentration value of the acetone released from
   An index value determination system including an index value determining means for determining an index value having a correlation with the mitochondrial activity of the subject using at least the obtained concentration value of acetone.
2. In the concentration value acquisition means, a reference concentration value of acetone released from a subject who has not ingested the acetone-generating species is acquired.
   The index value determining system according to claim 1, wherein in the index value determining means, the rate of increase in acetone concentration in a predetermined section from the reference concentration value to the maximum concentration value is determined as the index value.
3. In the index value determining means, after the concentration value of acetone reaches the maximum concentration value, the concentration value within a predetermined range is maintained for a certain period of time, and the minimum intake amount of the acetone-generating species is used as the index value. The index value determination system according to claim 1.
4. The index value determination according to any one of claims 1 to 3, wherein the subject who has ingested at least one selected from the acetone-producing species is ingesting nutrients together with the acetone-generating species. system.
5. The index value determination system according to any one of claims 1 to 4,
   An activity evaluation means for evaluating the mitochondrial activity of the subject based on the determined index value is provided.
   A mitochondrial activity evaluation system for evaluating the mitochondrial activity of a subject by comparing the determined index value with a past index value for the same subject in the activity evaluation means.
6. A method for determining an index value having a correlation with the mitochondrial activity of the subject by using the index value determination system according to any one of claims 1 to 4.
   A concentration value acquisition step of continuously or intermittently acquiring the concentration value of the acetone released from the subject who ingested at least one selected from the acetone-generating species.
   An index value determination method for performing an index value determination step of determining the index value having a correlation with the mitochondrial activity of the subject using at least the acquired concentration value of acetone.
7. A method for evaluating the mitochondrial activity of a subject using the mitochondrial activity evaluation system according to claim 5.
   A concentration value acquisition step of continuously or intermittently acquiring the concentration value of the acetone released from the subject who ingested at least one selected from the acetone-generating species.
   An index value determination step for determining the index value having a correlation with the mitochondrial activity of the subject using at least the obtained concentration value of acetone.
   Based on the determined index value, an activity evaluation step for evaluating the mitochondrial activity of the subject is performed.
   A method for evaluating mitochondrial activity in which the determined index value is compared with a past index value for the same subject in the activity evaluation step, and the mitochondrial activity of the subject is evaluated.
8. Subjects who ingested at least one selected from 3-hydroxybutyric acid, 3-hydroxybutyrate, 3-hydroxybutyric acid ester, and acetoacetic acid, which are acetone-generating species that are finally decomposed in the body to generate acetone. A concentration value acquisition step for continuously or intermittently acquiring the concentration value of the acetone released from
   An index value determination method for performing an index value determination step of determining an index value having a correlation with the mitochondrial activity of the subject using at least the acquired concentration value of acetone.
9. In the concentration value acquisition step, a reference concentration value of acetone released from a subject who has not ingested the acetone-generating species is acquired.
   The index value determination method according to claim 8, wherein in the index value determination step, the rate of increase in acetone concentration in a predetermined section from the reference concentration value to the maximum concentration value is determined as the index value.
10. In the index value determination step, after the concentration value of acetone reaches the maximum concentration value, the concentration value within a predetermined range is maintained for a certain period of time, and the minimum intake amount of the acetone-generating species is used as the index value. The index value determining method according to claim 8.
11. The index value determination according to any one of claims 8 to 10, wherein the subject who has ingested at least one selected from the acetone-producing species is ingesting nutrients together with the acetone-generating species. Method.
12. After determining the index value by the index value determining method according to any one of claims 8 to 11,
    Based on the determined index value, an activity evaluation step for evaluating the mitochondrial activity of the subject is executed.
    A method for evaluating mitochondrial activity in which the determined index value is compared with a past index value for the same subject in the activity evaluation step to evaluate the mitochondrial activity of the subject.

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