Aging prevention method

Abstract

Provided is an aging prevention method with which it is possible to provide an anti-aging effect easily in a short period of time.　By having a subject undergo fasting for a predetermined period (about 48 hours) to elongate the length of telomeres in the subject, to increase the expression level of Sirt1, which is an anti-aging gene, and activate the same, and to further lower the concentration of 8-hydroxydeoxyguanosine and reduce oxidative stress, it is possible to rejuvenate the subject at the genetic level and provide an anti-aging effect in a short period of time of about 48 hours by a simple method which is fasting.

Description

Anti-aging method

[0001] The present invention relates to an anti-aging method, and particularly to an anti-aging method capable of obtaining an anti-aging effect simply and in a short period of time.

[0002] In recent years, various proposals have been made regarding anti-aging methods (see, for example, Patent Document 1).

[0003] International Publication No. 2015 / 030149

[0004] However, the anti-aging method described in Patent Document 1 has problems such as being complicated and requiring a lot of time.

[0005] The present invention has been made to solve the above problems, and an object thereof is to provide an anti-aging method capable of obtaining an anti-aging effect simply and in a short period of time.

[0006] In order to achieve the above object, the anti-aging method according to the present invention is characterized in that a subject is made to fast for a predetermined period, and the aging of the subject is prevented by increasing the length of telomeres in the subject.

[0007] In the above anti-aging method, the subject may be made to fast for the predetermined period, and the aging of the subject may be prevented by increasing the expression level of Sirt1 in the subject.

[0008] In the above anti-aging method, the subject may be made to fast for the predetermined period, and the aging of the subject may be prevented by decreasing the concentration of 8-hydroxydeoxyguanosine in the subject.

[0009] In the above anti-aging method, the subject may be made to fast for approximately 36 hours or more and approximately 72 hours or less.

[0010] In the above anti-aging method, the subject may be made to fast for the predetermined period, and the aging of the subject may be prevented by improving the epigenetic clock in the subject.

[0011] In the above-described anti-aging method, the subject may be required to fast for approximately 48 hours.

[0012] According to the present invention, it is possible to provide an anti-aging method that can achieve anti-aging effects easily and in a short period of time.

[0013] This graph shows the telomere length of healthy individuals before and after fasting. This graph shows the expression level of Sirt1 in healthy individuals before and after fasting. This graph shows the expression level of Rubicon in healthy individuals before and after fasting. This graph shows the concentration of 8-hydroxydeoxyguanosine in healthy individuals before and after fasting. This graph shows the telomere length of prostate cancer survivors before and after fasting. This graph shows the expression level of Sirt1 in prostate cancer survivors before and after fasting. This graph shows the expression level of Rubicon in prostate cancer survivors before and after fasting. This graph shows the concentration of 8-hydroxydeoxyguanosine in prostate cancer survivors before and after fasting. (a) is a graph showing the telomere length of healthy individuals at the first and second timings, (b) is a graph showing the expression level of Sirt1 in healthy individuals at the first and second timings, and (c) is a graph showing the expression level of Rubicon in healthy individuals at the first and second timings. This graph shows the epigenetic age of healthy individuals before and after fasting.

[0014] The following describes embodiments for carrying out the present invention.

[0015] First, the anti-aging method according to an embodiment of the present invention will be described with reference to the drawings.

[0016] In recent years, fasting, which involves abstaining from food for a certain period, has become popular, primarily with the aim of resting the internal organs, which have become fatigued due to irregular eating habits, and restoring the body to a normal rhythm. The inventor of this invention considered whether fasting might also be effective in preventing aging, and conducted the following test. [Test 1]

[0017] In Study 1, 14 healthy individuals (10 males and 4 females, average age 54 years) underwent a fasting period of approximately 48 hours. Blood samples were taken before fasting and immediately after fasting (morning of the final day), and telomere length (TL), Sirt1 and Rubicon expression levels, and 8-hydroxydeoxyguanosine (8-OHdG) concentration (ng / ml) were measured.

[0018] Telomeres are repeating DNA sequences at the ends of chromosomes that are associated with cellular aging and are known as one of the indicators of biological aging. Telomeres shorten with each cell division, and longer telomeres are associated with longer lifespans. Telomere length is related to appearance and is also associated with the frequency of depression, arteriosclerosis, and heart disease. Factors that lengthen telomeres include testosterone, exercise, and meditation, while factors that shorten them include smoking, pessimism, and psychological stress. Telomeres shorten faster in men than in women.

[0019] Sirt1 is a type of sirtuin gene, also known as a longevity gene (anti-aging gene). Sirt1 functions as an NAD+-dependent protein deacetylase and controls a wide range of physiological functions by interacting with various proteins in the body. Activating Sirt1 can enhance anti-aging effects and cellular stress resistance.

[0020] Rubicon is a factor that suppresses autophagy, a mechanism in cells that breaks down intracellular proteins. As we age, the amount of Rubicon increases, and the function of autophagy declines. By suppressing Rubicon, it is possible to control aging, prevent age-related diseases that become more common with age, and extend healthy life expectancy.

[0021] 8-hydroxydeoxyguanosine is produced when guanine bases in DNA (deoxyribonucleic acid) are damaged by reactive oxygen species due to ultraviolet radiation or stress. 8-hydroxydeoxyguanosine is known as a biomarker that reflects oxidative stress, which is considered a cause of aging.

[0022] Figure 1 is a graph showing the telomere lengths of healthy individuals before and after fasting. In Figure 1, of the pairs of line segments corresponding to each of the 14 healthy individuals ((1) to (14)), the left line segment shows the telomere length TL of the healthy individual before fasting, and the right line segment shows the telomere length TL of the healthy individual immediately after fasting (morning of the final day).

[0023] As shown in Figure 1, of the 14 healthy subjects, 9 showed an increase in telomere length (TL) immediately after fasting (morning of the final day) compared to before fasting, while 5 showed a decrease in telomere length (TL). In other words, more than half of the 14 healthy subjects (9 people) showed an increase in telomere length (TL), indicating a life-extending effect (n=14, before fasting 0.89 ± 0.12 (mean ± SD), immediately after fasting 0.93 ± 0.15 (mean ± SD), P=0.3).

[0024] Figure 2 is a graph showing the expression levels of Sirt1 in healthy individuals before and after fasting. In Figure 2, of the pairs of line segments corresponding to each of the 14 healthy individuals ((1) to (14)), the left line segment shows the expression level of Sirt1 in healthy individuals before fasting, and the right line segment shows the expression level of Sirt1 in healthy individuals immediately after fasting (morning of the final day).

[0025] As shown in Figure 2, of the 14 healthy subjects, 11 showed an increase in Sirt1 expression immediately after fasting (morning of the final day) compared to before fasting, while 3 showed a decrease in Sirt1 expression. However, the change in Sirt1 expression in the 3 subjects who experienced a decrease can be considered within the margin of error and can be seen as stable. In contrast, of the 11 subjects whose Sirt1 expression increased, the expression level immediately after fasting in 4 subjects was more than double the expression level before fasting. From these test results, it was concluded that approximately 48 hours of fasting significantly increased Sirt1 expression in healthy subjects, and activation of Sirt1, an anti-aging gene, was observed (n=14, before fasting 0.65 ± 0.25 (mean ± SD), immediately after fasting 1.00 ± 0.39 (mean ± SD), P=0.0067).

[0026] Figure 3 is a graph showing the expression levels of Rubicon in healthy individuals before and after fasting. In Figure 3, of the pairs of line segments corresponding to each of the 14 healthy individuals ((1) to (14)), the left line segment shows the expression level of Rubicon in healthy individuals before fasting, and the right line segment shows the expression level of Rubicon in healthy individuals immediately after fasting (morning of the final day).

[0027] As shown in Figure 3, all 14 healthy subjects showed a decrease in Rubicon expression immediately after fasting (morning of the final day) compared to before fasting. Of the 13 subjects whose Rubicon expression decreased, the expression level immediately after fasting in 10 subjects was less than half of the expression level before fasting. From these test results, it can be seen that approximately 48 hours of fasting significantly reduced the expression level of Rubicon in healthy subjects. In other words, suppression of Rubicon was observed with approximately 48 hours of fasting (n=14, before fasting 1.62 ± 1.20 (mean ± SD), immediately after fasting 0.48 ± 0.35 (mean ± SD), P < 0.001).

[0028] Figure 4 is a graph showing the concentration of 8-hydroxydeoxyguanosine in healthy individuals before and after fasting. In Figure 4, of the pairs of line segments corresponding to each of the 14 healthy individuals ((1) to (14)), the left line segment shows the concentration of 8-hydroxydeoxyguanosine in healthy individuals before fasting, and the right line segment shows the concentration of 8-hydroxydeoxyguanosine in healthy individuals immediately after fasting (morning of the final day).

[0029] As shown in Figure 4, of the 14 healthy subjects, 12 showed a decrease in 8-hydroxydeoxyguanosine concentration immediately after fasting (morning of the final day) compared to before fasting, while 2 showed an increase in 8-hydroxydeoxyguanosine concentration. However, the change in the two subjects whose 8-hydroxydeoxyguanosine concentration increased can be considered within the margin of error and can be seen as stable. From these test results, it was found that approximately 48 hours of fasting significantly decreased the concentration of 8-hydroxydeoxyguanosine in healthy subjects, and a decrease in biomarkers reflecting oxidative stress, which is considered a cause of aging, was observed (n=14 Before fasting 7.62 ± 6.59 (mean ± SD) Immediately after fasting 6.19 ± 4.12 (mean ± SD) P=0.011). [Test 2]

[0030] In Study 2, 14 prostate cancer survivors (14 men, average age 72 years) underwent a fast of approximately 48 hours. Blood samples were taken before fasting, immediately after fasting (morning of the final day), and approximately two weeks after fasting, and telomere length, Sirt1 and rubicon expression levels, and 8-hydroxydeoxyguanosine concentration were measured.

[0031] Figure 5 is a graph showing the telomere lengths of prostate cancer survivors before and after fasting. In Figure 5, of the three line segments corresponding to each of the 14 prostate cancer survivors ((1) to (14)), the left line segment shows the telomere length TL of the prostate cancer survivor before fasting, the middle line segment shows the telomere length TL of the prostate cancer survivor immediately after fasting (morning of the last day), and the right line segment shows the telomere length TL of the prostate cancer survivor approximately two weeks after fasting.

[0032] As shown in Figure 5, of the 14 prostate cancer survivors who were subjects, 13 had longer telomere lengths (TL) immediately after fasting (morning of the final day) and approximately two weeks after fasting compared to before fasting. In the remaining one subject, the telomere length (TL) was slightly shorter immediately after fasting (morning of the final day) (however, the amount of change can be considered within the margin of error and can be seen as remaining stable), but approximately two weeks after fasting, the telomere length (TL) was longer than before fasting. Specifically, approximately two weeks after fasting, all 14 prostate cancer survivors in the study showed longer telomere lengths (TL) compared to before fasting, demonstrating a life-extending effect (n=14, before fasting 0.71 ± 0.11 (mean ± SD), immediately after fasting 0.77 ± 0.10 (mean ± SD), 2 weeks after fasting 0.79 ± 0.10 (mean ± SD), P < 0.001 (before fasting vs. immediately after fasting), P < 0.001 (before fasting vs. 2 weeks after fasting)).

[0033] Figure 6 is a graph showing the expression levels of Sirt1 in prostate cancer survivors before and after fasting. In Figure 6, of the three line segments corresponding to each of the 14 prostate cancer survivors ((1) to (14)), the left line segment shows the expression level of Sirt1 in prostate cancer survivors before fasting, the middle line segment shows the expression level of Sirt1 in prostate cancer survivors immediately after fasting (morning of the final day), and the right line segment shows the expression level of Sirt1 in prostate cancer survivors approximately two weeks after fasting.

[0034] As shown in Figure 6, of the 14 prostate cancer survivors who were subjects, 13 showed an increase in Sirt1 expression immediately after fasting (morning of the final day) compared to before fasting, while one showed a decrease in Sirt1 expression. However, approximately two weeks after fasting, all 14 prostate cancer survivors showed an increase in Sirt1 expression compared to before fasting, and in half of them, the expression level approximately two weeks after fasting was more than double the expression level before fasting. Based on the above test results, approximately 48 hours of fasting significantly increased Sirt1 expression in prostate cancer survivors, indicating activation of Sirt1, an anti-aging gene (n=14, before fasting 0.65 ± 0.30 (mean ± SD), immediately after fasting 1.02 ± 0.47 (mean ± SD), 2 weeks after fasting 1.33 ± 0.49 (mean ± SD), P < 0.001 (before fasting vs. immediately after fasting), P = 0.002 (before fasting vs. 2 weeks after fasting)).

[0035] Figure 7 is a graph showing the expression levels of Rubicon in prostate cancer survivors before and after fasting. In Figure 7, of the three line segments corresponding to each of the 14 prostate cancer survivors ((1) to (14)), the left line segment shows the expression level of Rubicon in prostate cancer survivors before fasting, the middle line segment shows the expression level of Rubicon in prostate cancer survivors immediately after fasting (morning of the final day), and the right line segment shows the expression level of Rubicon in prostate cancer survivors approximately two weeks after fasting.

[0036] As shown in Figure 7, of the 14 prostate cancer survivors who were subjects, 12 showed a decrease in Rubicon expression immediately after fasting (morning of the final day) compared to before fasting, while 2 showed an increase in Rubicon expression before and after fasting. However, the change in Rubicon expression in the two subjects who showed an increase can be considered within the margin of error and can be seen as a plateau. However, approximately two weeks after fasting, all 14 prostate cancer survivors showed an increase in Rubicon expression compared to before fasting (n=14, before fasting 0.51 ± 0.27 (mean ± SD), immediately after fasting 0.28 ± 0.20 (mean ± SD), 2 weeks after fasting 1.19 ± 0.67 (mean ± SD), P=0.002 (before fasting vs. immediately after fasting), P<0.001 (before fasting vs. 2 weeks after fasting)).

[0037] Figure 8 is a graph showing the concentration of 8-hydroxydeoxyguanosine in prostate cancer survivors before and after fasting. In Figure 8, of the three line segments corresponding to each of the 14 prostate cancer survivors ((1) to (14)), the left line segment shows the concentration of 8-hydroxydeoxyguanosine in the prostate cancer survivors before fasting, the middle line segment shows the concentration of 8-hydroxydeoxyguanosine in the prostate cancer survivors immediately after fasting (morning of the final day), and the right line segment shows the concentration of 8-hydroxydeoxyguanosine in the prostate cancer survivors approximately two weeks after fasting.

[0038] As shown in Figure 8, of the 14 prostate cancer survivors who were subjects, 13 showed a decrease in 8-hydroxydeoxyguanosine concentration immediately after fasting (morning of the final day) compared to before fasting, while one showed almost no change and remained stable. Approximately two weeks after fasting, all 14 prostate cancer survivors showed a decrease in 8-hydroxydeoxyguanosine concentration compared to before fasting. Based on the above test results, approximately 48 hours of fasting significantly reduced the concentration of 8-hydroxydeoxyguanosine in prostate cancer survivors, and a decrease in biomarkers reflecting oxidative stress, which is considered a cause of aging, was observed (n=14, before fasting 4.70 ± 0.95 (mean ± SD), immediately after fasting 4.17 ± 0.77 (mean ± SD), 2 weeks after fasting 3.67 ± 0.76 (mean ± SD), P<0.001 (before fasting vs. immediately after fasting), P<0.001 (before fasting vs. 2 weeks after fasting)). [Study 3]

[0039] In Study 3, blood samples were taken from four healthy individuals at two points: the first timing and the second timing approximately 40 hours after the first timing without fasting. Telomere length and Sirt1 and Rubicon expression levels were measured.

[0040] Figure 9(a) is a graph showing the telomere lengths of healthy individuals at the first and second timings, Figure 9(b) is a graph showing the expression levels of Sirt1 in healthy individuals at the first and second timings, and Figure 9(c) is a graph showing the expression levels of Rubicon in healthy individuals at the first and second timings. In Figures 9(a) to (c), of the pairs of line segments corresponding to each of the four healthy individuals (119 to 122), the left line segment shows the telomere length TL and the expression levels of Sirt1 and Rubicon in healthy individuals before fasting, respectively, while the right line segment shows the telomere length TL and the expression levels of Sirt1 and Rubicon in healthy individuals immediately after fasting (morning of the final day), respectively.

[0041] As shown in FIGS. 9(a) to 9(c), for four healthy subjects, there were no changes in either the telomere length TL, or the expression levels of Sirt1 and Rubicon at the first timing and the second timing. From the above test results, it was found that without fasting, there were no changes in either the telomere length, or the expression levels of Sirt1 and Rubicon.

[0042] From the comparison between the results of Tests 1 and 2 and the results of Test 3, it was found that fasting affects the telomere length TL of the subjects, the expression levels of Sirt1 and Rubicon, and the concentration of 8-hydroxydeoxyguanosine.

[0043] And from the results of Tests 1 and 2, by fasting, the telomere length TL becomes longer in both healthy subjects and prostate cancer survivors, and a lifespan-extending effect of fasting is recognized. Also, by fasting, the expression level of Sirt1, which is an anti-aging gene, increases in both healthy subjects and prostate cancer survivors, and an anti-aging effect is recognized. Furthermore, by fasting, the concentration of 8-hydroxydeoxyguanosine decreases in both healthy subjects and prostate cancer survivors, and a decrease in the biomarker reflecting oxidative stress, which is a cause of aging, is recognized. Evidence that one can regain about 10 years of youth from genes was obtained by such a short-term fasting of about 48 hours. [Test 4]

[0044] In Test 4, 13 prostate cancer survivors aged 66 to 76 years (average age 72 years) were subjected to a fasting of about 48 hours, and the epigenetic clock was measured before fasting and two weeks after fasting.

[0045] The epigenetic clock is a technique for evaluating biological age by analyzing DNA methylation patterns. In this test, the epigenetic age was evaluated using GrimAgeV2.

[0046] FIG. 10 is a graph showing the epigenetic age of healthy subjects before and after fasting.

[0047] As shown in Fig. 10, among 13 prostate cancer survivors who were the subjects, 4 (30.8%) showed a rejuvenation with an epigenetic age reversal of more than 1 year, 5 (38.5%) showed a rejuvenation with an epigenetic age reversal of 0 to 1 year, and 4 (30.8%) had an epigenetic age advancement of 0 to 1 year. There were no participants with an epigenetic age advancement of more than 1 year. The average difference in the acceleration of epigenetic age between after the end of fasting (the median was 9 days later) and baseline was -0.71, indicating a moderately significant rejuvenation (improvement in epigenetic age).

[0048] As described above, according to the anti-aging method according to this embodiment, the subject is made to fast for a predetermined period (approximately 48 hours), the length of telomeres in the subject is increased, the expression level of Sirt1, which is an anti-aging gene, is increased and activated, the epigenetic clock, which is the biological age, is rejuvenated, the expression level of Rubicon, which is an autophagy inhibitor, is suppressed and decreased, and furthermore, the concentration of 8-hydroxydeoxyguanosine, which is an oxidative stress marker, is decreased to reduce oxidative stress. By simultaneously controlling the main molecular indicators of aging such as these, with a simple method of fasting, it is possible to rejuvenate at the gene level in a short period of approximately 48 hours and obtain an anti-aging effect. These effects have been confirmed for a wide range of subjects such as healthy people, the elderly, and cancer survivors, and since it is possible to reverse aging at the gene level without using drugs, it is possible to non-invasively and safely extend the healthy life span.

[0049] The anti-aging method according to this embodiment is used for extending the healthy life span, preventing metabolic diseases, neurodegenerative diseases, etc. Also, the anti-aging method according to this embodiment can be used in combination with nutrients, exercise, and / or meditation, etc. Furthermore, the anti-aging method according to this embodiment can be provided as foods, supplements, digital programs, etc.

[0050] Note that the present invention is not limited to the above-described embodiment, and various modifications and applications are possible. Hereinafter, modified forms of the above-described embodiment applicable to the present invention will be described.

[0051] In the above embodiment, the subjects were instructed to fast for a predetermined period (approximately 48 hours), but the present invention is not limited thereto, and any duration for which the effects of fasting become apparent is acceptable. Preferably, it is approximately 36 hours or more and approximately 72 hours, but more preferably, it is approximately 48 hours, as in the above embodiment.

[0052] Furthermore, the present invention can be implemented in various forms and modified without departing from the broad spirit and scope of the invention. The above-described embodiments are for illustrative purposes only and do not limit the scope of the invention.

[0053] This invention has broad applications in the fields of medicine, preventive medicine, corporate health management, the wellness industry, supplement development, and digital health. Furthermore, it possesses high safety as a non-pharmacological intervention and has extremely high social and economic value.

Claims

1. An anti-aging method characterized by having a subject fast for a predetermined period of time, thereby increasing the length of telomeres within the subject and preventing aging.

2. The anti-aging method according to claim 1, characterized in that the subject is subjected to fasting for a predetermined period of time, thereby increasing the expression level of Sirt1 in the subject and preventing aging of the subject.

3. The anti-aging method according to claim 1 or 2, characterized in that the subject is subjected to fasting for a predetermined period, thereby reducing the concentration of 8-hydroxydeoxyguanosine in the subject and preventing aging.

4. The anti-aging method according to claim 1, characterized in that the subject is instructed to fast for approximately 36 hours or more and approximately 72 hours or less.

5. The anti-aging method according to claim 4, characterized in that the subject is subjected to fasting for approximately 48 hours.

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