スペルミジンの老化抑制および寿命延長の効果に関するものです。以下にその主要な内容を要約します。
1. 老化と加齢の違い
- 加齢は単なる年齢の経過であり、物理的に止められない。
- 老化は身体の機能低下であり、食生活や生活習慣で遅くすることができる。
2. 食事と老化
- 地中海食や沖縄の食事は長寿と関連している。
- 抗酸化物質、ポリフェノール、ポリアミン（例：スペルミジン）を含む食事が老化を抑制する。
- 西洋型の食事は健康に悪影響を与える。
3. スペルミジンの効果
- ポリアミンの一種であるスペルミジンは、細胞増殖を助ける重要な役割を果たす。
- 発毛促進、抗炎症、動脈硬化抑制などの効果があり、抗老化サプリメントとして注目されている。
- 酵母、線虫、ハエ、マウスなどで寿命を延ばすことが示されている。
4. スペルミジンとオートファジー
- オートファジーは細胞内のタンパク質や小器官を分解・再利用するプロセス。
- オートファジーの活性化は老化抑制に重要で、スペルミジンはオートファジーを誘発する。
- オートファジーを通じて、異常タンパク質や損傷ミトコンドリアの除去、がんや糖尿病などの疾患発症を抑制。
5. スペルミジンとテロメア
- テロメアは染色体末端の構造で、細胞分裂の限界を決める。
- スペルミジンはテロメア短縮を抑制し、細胞の寿命を延ばす可能性がある。
6. スペルミジンの摂取
- スペルミジンは納豆、チーズ、小麦胚芽などに多く含まれる。
- 加齢とともに体内のスペルミジン合成量は減少するため、食品やサプリメントでの補給が推奨される。
- 小麦胚芽を材料にしたサプリメントが利用されている。
7. 研究とエビデンス
- スペルミジン摂取が多いと、45歳以上の集団で死亡率が半分以下になることが示されている。
- 抗老化効果は、オートファジーの活性化とテロメア短縮の抑制に関連している。
スペルミジンは、老化を抑制し寿命を延ばす可能性を持つ物質として、多くの研究で支持されています。特にオートファジーの活性化とテロメアの保持が重要なメカニズムとして考えられています。
Sure, I will translate the provided text into English. Here is the translation:
Spermidine Inhibits Aging and Extends Lifespan
10
Kazunori Fukuda | Ginza Tokyo Clinic
Kazunori Fukuda | Ginza Tokyo Clinic
November 22, 2021, 16:41
Revitalizing Mitochondria Activation Techniques 47
This article explains pharmaceuticals and supplements that rejuvenate the body by activating mitochondria.
[The Contents of Your Diet Affect the Rate of Aging and Lifespan]
Living organisms age as they get older. "Aging" refers to the passage of time since birth and is synonymous with age. Therefore, aging cannot be stopped or reversed. It's impossible to turn back time physically, just like we can't go back to the past with a time machine.
On the other hand, "aging" refers to the decline in bodily functions that accompany getting older after reaching adulthood. The rate and degree of aging vary among individuals. The speed of aging can be artificially slowed down through diet and lifestyle choices. This means it is possible to artificially extend lifespan. Additionally, it is possible to reverse the level of aging to a younger state, meaning rejuvenation is possible.
When considering methods to extend lifespan artificially, diet is the most important factor. For example, it has been pointed out that Mediterranean and Okinawan diets are both associated with longevity and reduced risk of chronic aging-related diseases.
Both diets include the intake of a wide range of antioxidants from fruits and vegetables, polyphenols (such as resveratrol), and polyamines (such as spermidine and spermine), as well as moderate to large amounts of seafood and fish (containing astaxanthin and healthy fatty acids).
In contrast, Western diets, characterized by high consumption of unhealthy fatty acids (saturated fatty acids), red meat, sweets, and highly processed foods, have been pointed out to potentially have negative health impacts.
[Spermidine Supplementation Inhibits Aging and Extends Lifespan]
Polyamines are substances with two or more amino groups (-NH2) and are synthesized from amino acids in the body. There are more than 20 types of polyamines in the body, with spermidine, spermine, and putrescine being representative examples (see figure below).
Figure 1: Polyamines have two or more amino groups (-NH2).
Polyamines are actively synthesized in all animal and human cells during growth periods. They promote the synthesis of nucleic acids and proteins. Without polyamines, cells cannot proliferate. Polyamines bind strongly to nucleic acids with positive charges due to their amino groups and are thought to be involved in maintaining the three-dimensional structure of nucleic acids. In the body, they are found abundantly in tissues that produce sperm and enzymes, such as the prostate, pancreas, and salivary glands.
Furthermore, spermidine possesses various functions, including promoting hair growth and having anti-inflammatory effects that suppress arteriosclerosis. It promotes the growth and shine of hair and nails, making it a noteworthy supplement material for beauty and anti-aging.
Exogenous supplementation of spermidine extends lifespan and health span in various species, including yeast, nematodes, flies, and mice. In humans, spermidine levels decline with age, suggesting a possible association between decreased endogenous spermidine concentration and age-related decline in bodily functions.
Recent epidemiological data support this concept, showing that increased intake of polyamines from spermidine-rich foods reduces mortality rates associated with cardiovascular disease and cancer. Multiple epidemiological studies have revealed that higher dietary spermidine intake is associated with longer lifespan. Here are some reports:
Higher spermidine intake is linked to lower mortality: a prospective population-based study.
Am J Clin Nutr. 2018 Aug 1;108(2):371-380.
[Excerpt of the summary]
Background: In several animal models, spermidine administration has been shown to increase survival rates.
Objective: To examine the potential association between dietary spermidine content and human mortality rates.
Methods: This prospective cohort study included 829 participants aged 45-84 years, with 49.9% being male. Diet was assessed repeatedly using food frequency questionnaires (evaluating 2540 items) conducted by nutritionists in 1995, 2000, 2005, and 2010. During the follow-up period from 1995 to 2015, 341 participants died.
Results: Mortality rates from all causes (deaths per 1000 person-years) were 40.5 (95% CI: 36.1-44.7) for the lowest tertile of spermidine intake, 23.7 (95% CI: 20.0-27.0) for the middle tertile, and 15.1 (95% CI: 12.6-17.8) for the highest tertile. The cumulative mortality rate over 20 years, adjusted for age, sex, and caloric intake, was 0.48 (95% CI: 0.45-0.51) for the lowest tertile, 0.41 (95% CI: 0.38-0.45) for the middle tertile, and 0.38 (95% CI: 0.34-0.41) for the highest tertile. The hazard ratio for all-cause mortality, adjusted for age, sex, and calorie intake, was 0.74 (95% CI: 0.66-0.83; P < 0.001) for an increase of one standard deviation in spermidine intake. The difference in mortality risk between the highest and lowest tertiles of spermidine intake corresponded to an age difference of 5.7 years (95% CI: 3.6-8.1 years).
Conclusion: Our findings provide epidemiological support for the concept that spermidine-rich diets are associated with increased human survival rates.
Higher spermidine intake suggests that the mortality rate over 20 years for individuals aged 45 and above could be less than half. This implies that higher spermidine intake could potentially extend lifespan by over five years.
[Spermidine Activates Autophagy to Rejuvenate Cells]
Proteins within cells are constantly being degraded and replaced with new proteins. This rejuvenation of proteins is significantly driven by a phenomenon called autophagy.
Autophagy, derived from the Greek words "auto" (self) and "phagy" (eating), literally means "self-eating." In Japanese, it is translated as "self-eating action." Autophagy acts as an intracellular recycling mechanism that gradually degrades parts of the cell.
Periodic fasting (abstinence from food) or continuous caloric restriction can rejuvenate the body. The reason is that fasting or caloric restriction enhances autophagy, which rejuvenates cells.
Autophagy is a mechanism where intracellular proteins and organelles are enclosed in a double-membrane structure and transported to lysosomes for degradation.
When cells are subjected to starvation conditions, flat vesicles called isolation membranes appear in the cytoplasm. These membranes capture abnormal proteins and organelles in the cytoplasm as they elongate, eventually fusing at the ends to form autophagosomes. Autophagosomes fuse with lysosomes, and the contents are degraded. The resulting amino acids and fatty acids are reused as nutrients (see figure below).
Figure 2: A flat vesicle called an isolation membrane appears from the endoplasmic reticulum (①), capturing abnormal proteins and organelles (②). The membrane elongates, engulfing parts of the cytoplasm, and fuses at the ends to form an autophagosome (③). Autophagosomes contain large intracellular organelles like mitochondria. Autophagosomes fuse with lysosomes (④), degrading the contents (⑤). The amino acids, fatty acids, and nucleic acids obtained from autophagy are reused as nutrients.
Cells use autophagy to degrade and recycle intracellular proteins and organelles (mitochondria and endoplasmic reticulum) during nutrient deprivation, obtaining the necessary energy and amino acids for survival.
Moreover, autophagy removes waste products, damaged mitochondria, pathogens, and abnormal proteins, thus inhibiting the onset of various diseases such as neurodegenerative diseases, cancer, diabetes, heart failure, various inflammations, and infections. This means autophagy removes aging components within cells, rejuvenating them. The mechanism by which fasting rejuvenates cells is also crucially linked to the enhancement of autophagy.
Inhibition of autophagy increases the likelihood of tumor formation, as the accumulation of abnormal proteins and defective mitochondria within cells triggers it.
Exogenous spermidine supplementation exerts various beneficial effects on aging and age-related diseases in different model organisms, including mice. For example, spermidine intake extends lifespan, protects the heart and nervous system, stimulates antitumor immune responses, and avoids immune aging by promoting memory T cell formation.
Many of these anti-aging effects are thought to be related to spermidine's ability to ensure protein homeostasis through the activation of autophagy. Spermidine induces autophagy by inhibiting several acetyltransferases, including EP300, a major negative regulator of autophagy.
Genetic modifications that make autophagy less likely negate the beneficial effects of spermidine on lifespan. This indicates that spermidine's lifespan extension effect involves the activation of autophagy.
[Spermidine Inhibits Telomere Shortening to Extend Lifespan]
While the primary mechanism of spermidine's anti-aging effects is believed to be the induction of autophagy, there are also reports of mechanisms that inhibit telomere shortening and extend lifespan. Here is one such report