A Comprehensive Guide to 6 Popular Anti-Aging Ingredients: NMN, AKG, PQQ, Urolithin A, Ergothioneine, and Spermidine!

01 NMN: Repairing DNA, Boosting NAD+

Dr. Mark Hyman, a functional medicine expert and former personal physician to US President Bill Clinton, has publicly recommended supplementing with NMN to increase NAD+ levels. Actress Qin Lan has also shared that she ensures daily NMN intake.

As we age, DNA damage increases. The DNA repair process consumes large amounts of NAD+. While the body's demand for NAD+ increases, its own ability to synthesize NAD+ declines, leading to a severe NAD+ deficiency. This ultimately causes decreased energy levels and declining bodily functions, which is a primary reason for aging.

NMN is a derivative of Vitamin B3, naturally present in human cells. As a key precursor to NAD+, NMN participates in cellular energy metabolism and various physiological processes. NMN content in food is only 0.25~1.88 mg per 100 grams, making dietary intake limited. This has made NMN supplements highly sought after globally, and the consensus is that NMN can delay aging by increasing NAD+ levels.

A Harvard Medical School research team published a study in a Cell sub-journal where they treated 22-month-old mice (equivalent to 60 human years) with NMN for one week. The mice showed key indicators of mitochondrial stability and muscle health similar to 6-month-old mice (equivalent to 20 human years). Research found that NAD+ levels steadily decline with age. Starting around age 30, the body's NAD+ levels decrease with age. By age 60, NAD+ levels are less than a quarter of those in young people. This means that after 60, many biochemical metabolic reactions cannot proceed efficiently, leading to more health issues with increasing age. Restoring NAD+ levels in a timely manner can promote health and extend lifespan. Relevant human studies show that NMN can improve sleep quality, reduce fatigue, enhance physical performance in the elderly, and increase NAD+ levels.

Efficacy Guide:

1. Target Audience – Middle-aged adults: Prioritize natural methods like intermittent fasting, adjusting sleep schedules, and regular exercise to boost endogenous NMN production. Elderly: Appropriate NMN supplementation may help increase NAD+ levels, thereby improving fatigue and enhancing daily activity capacity.

2. Gender – Men have significantly higher whole blood NAD+ levels than women. Women may therefore have a greater need to supplement with NMN to increase their NAD+ levels. This is especially beneficial for menopausal women. Menopause is an inevitable stage accompanied by hormonal changes and various discomforts like hot flashes, insomnia, and mood swings. As a supplement, NMN can help alleviate menopausal symptoms by boosting energy levels and improving hormonal balance.

3. Effects – A common dosage for NMN is 250mg/d, with afternoon intake potentially being more effective. Typically, individuals with poorer metabolism or lower immune function may feel the effects of NMN more quickly, including increased energy and reduced fatigue. Those with better metabolism might require longer supplementation to see effects.

02 AKG: Multi-dimensional Anti-Aging, Promotes Collagen Synthesis

Bryan Johnson, a 46-year-old Silicon Valley billionaire, started an anti-aging experiment called the "Blueprint Project" in 2021. His daily supplement list includes AKG. The human clinical recommendation is to maintain a daily intake of 2g Ca-AKG.

AKG is a metabolite in the Tricarboxylic Acid (TCA) Cycle. It can produce energy within the body, synthesize essential proteins, improve mitochondrial function, enhance cellular repair capacity, and extend healthspan. However, as we age, AKG synthesis ability declines. Additionally, its metabolism is fast (less than 5 minutes), and it is not present in the human diet. Therefore, direct AKG intake is needed to maintain healthy bodily functions. AKG delays aging through multiple mechanisms, including reducing inflammation, enhancing antioxidant capacity, promoting DNA repair, and regulating autophagy.

In 2021, a study led by Professor Brian Kennedy, Director of the Centre for Healthy Longevity at the National University of Singapore, involved 42 healthy adults taking AKG complex supplements for 7 months. Astonishingly, their biological age decreased by 8 years. A 2023 review report indicated that AKG can promote skin hydration, stimulate collagen synthesis, support ROS detoxification ("antioxidant" effect), help restore normal blood calcium levels, accelerate wound healing, and promote muscle tissue repair.

Efficacy Guide:

1. Target Audience – People aged 30-35 and above: Stress from life and work causes bodily changes and organ damage. Simply put, stress increases the body's oxygen consumption. Increased oxygen consumption leads to excessive oxidative reactions in your own mitochondria. Supplementing with AKG is recommended to help enhance antioxidant capacity. Individuals with chronic diseases: AKG can address the root causes of chronic diseases by activating longevity proteins and repairing damaged DNA. Fitness enthusiasts and athletes: AKG helps control weight, promote protein synthesis, stimulate muscle growth, and enhance endurance, making it very suitable for this group.

2. Gender – A study on the dose- and sex-dependent effects of dietary AKG showed: In males, dietary supplementation with 10 mM AKG extended maximum lifespan, while in females, both 10 and 20 mM AKG extended median and maximum lifespan. Supplementing with substances like AKG can "charge" cells by increasing NAD+. Regarding sexual function regulation, NAD+ can boost testosterone, increase male hormones, improve sperm viability, and enhance male sexual function. It also promotes the repair and maintenance of female ovaries and uterus, restoring physiological functions and normalizing menstruation.

3. Effects – Individuals with poor gut health or metabolism may absorb and respond to AKG faster, while those with good digestion and absorption may not notice significant effects. Furthermore, AKG's anti-inflammatory effects are more pronounced in individuals with chronic inflammation.

03 PQQ: The Knight Guarding Mitochondrial Energy

PQQ is hailed as the "Key to Cellular Energy." It is a vitamin B-like compound and an essential coenzyme for mitochondrial biogenesis. By improving mitochondrial function, PQQ enhances the production efficiency of ATP (Adenosine Triphosphate), providing energy for cells. PQQ occurs naturally in various foods like breast milk, fermented foods, tea, papaya, and spinach, but its content is relatively low, making PQQ supplements a viable option.

Mitochondria are the cell's power plants, responsible for producing the energy cells need (closely related to our energy levels). PQQ is the first nutrient discovered that can promote the growth of new mitochondria. For those with chronic fatigue or compromised immune function, PQQ can significantly enhance mitochondrial activity and improve energy metabolism. PQQ is also an extremely powerful antioxidant with unique efficacy. It scavenges free radicals due to its antioxidant properties, reducing cellular damage. PQQ can improve brain cognition; it contains substances that aid memory, attention, and learning, sometimes called nootropics. When a group of elderly individuals took PQQ supplements daily for 12 weeks, their attention and memory abilities improved.

Efficacy Guide:

1. Target Audience – Suitable for individuals with low immunity, those who get sick easily, and people with high blood pressure. Generally, middle-aged and elderly individuals may experience effects more quickly. However, it's important to note that while PQQ has many benefits, it's not for everyone. It is not recommended for infants, young children, pregnant, or breastfeeding women. Additionally, individuals with growths (e.g., polyps, tumors) should consult a doctor.

2. Gender – Helps men improve feelings of fatigue and boost energy; helps women achieve a more youthful state and delay aging.

3. Effects – PQQ is used by the body as a redox agent, an antioxidant that reduces cell damage. It performs better than many other antioxidants. Human studies show that PQQ significantly improves attention and working memory and increases blood flow to the brain.

04 Urolithin A: Activates Cellular Autophagy, Slows Aging

Urolithin A (UA) is a natural compound. Pomegranate is a representative fruit rich in Urolithin A precursors. Rhonda Patrick, a well-known biomedical scientist and nutrition expert, includes Urolithin A in her morning supplement list. It is also a supplement endorsed by Maye Musk, mother of world's richest person Elon Musk. A US small-scale clinical trial found that taking a 500 mg supplement provided over 6 times the UA equivalent capacity compared to drinking 240 ml of pure pomegranate juice.

A 2016 study published in Nature Medicine found that Urolithin A is a mitochondrial modulator. It can potentially improve mitochondrial health by activating mitophagy and demonstrated that Urolithin A can restore the hematopoietic system, delay cellular senescence, and further reverse the regenerative capacity of blood cells, thereby exerting anti-aging effects. (It should be noted that ellagic acid and ellagitannins found in pomegranates, nuts, and some berries are metabolized by gut microbes to produce Urolithin A.)

Urolithin A is widely studied as an anti-aging supplement. On August 31, 2023, scientists from the University of Lausanne in Switzerland published research in the renowned journal Nature Aging. The results showed that Urolithin A restored the function of hematopoietic stem cells in aged mice (over 18 months old) to the level of young mice (8-12 weeks old). The scientists further explained that Urolithin A promoted mitochondrial autophagy and regeneration, thereby enhancing the vitality of hematopoietic stem cells, making them more "youthful," and consequently boosting immunity against viral infections. This means Urolithin A not only fights aging but also enhances immune function!

Efficacy Guide:

1. Target Audience – Elderly: Supplementing with Urolithin A could have a significant impact as it strengthens the hematopoietic and immune systems in the elderly, potentially reducing the risk of hematopoietic failure and enhancing immune surveillance; it also helps middle-aged and elderly individuals enhance muscle strength and physical performance.

2. Gender – Urolithin A enhances insulin sensitivity and lowers blood sugar levels, helping improve metabolic syndrome. For men, this aids in managing health risks specific to men, such as prostate cancer. Urolithin A has anti-inflammatory and anti-bacterial/viral properties, which may be more beneficial for women by helping alleviate some inflammation-related conditions associated with women's health, such as fibroids and endometriosis. It's important to note that specific health effects can vary based on individual differences (e.g., gut microbiota composition). Consulting a healthcare professional is recommended to ensure safety and suitability.

3. How to Obtain/Effects – It's not very feasible to obtain Urolithin A directly from the daily diet. While foods like pomegranates, raspberries, strawberries, pecans, and walnuts are rich in the precursor polyphenols, not everyone can convert these dietary polyphenols into Urolithin A. This requires specific gut bacteria. Research found that only 40% of people can naturally convert it, and the conversion amount likely varies between individuals. Fortunately, a June 2021 study in Nature pointed out that using Urolithin A supplements directly can overcome the gut microbiota limitation and allow you to benefit directly.

05 Ergothioneine: The Ace Antioxidant for Skin Care

Ergothioneine is a natural amino acid derivative widely recognized for its potent antioxidant and anti-inflammatory effects, helping protect cells from free radical and oxidative stress damage. Ergothioneine is naturally occurring but difficult for the body to synthesize on its own. It possesses important efficacy such as powerful antioxidant activity, cell protection, and activation of longevity genes, hence it's called the "Longevity Vitamin." Its main manifestations are in three areas:

1. Powerful Antioxidant: Ergothioneine is a potent antioxidant that neutralizes free radicals, preventing oxidative damage to cells. One study suggests that ergothioneine may represent a new vitamin, with physiological roles including antioxidant cell protection. (If our skin is oxidized by excessive free radicals, it ultimately undergoes carbonylation. Large numbers of free radicals indiscriminately attack (oxidize) normal cells and proteins in the skin. This slows down cell metabolism, causing the skin to lose elasticity and sag with age.)

2. Cellular and Mitochondrial Protection: Ergothioneine can penetrate cell membranes, enter cells directly, and provide protection to crucial organelles like mitochondria, reducing cell aging and apoptosis. Research shows that ergothioneine can effectively protect skin cells from UVB radiation-induced DNA damage in vitro and reduce UVB-induced apoptosis.

3. Moisturizing/Anti-aging Function: A 12-week randomized, double-blind, placebo-controlled, parallel-group trial evaluated skin hydration and facial condition in 80 healthy women. Results found that by week 8, skin moisture content at the temple was significantly higher in the ergothioneine group than the placebo group. By week 12, skin moisture content on the arm also increased significantly. After 12 weeks, facial wrinkle and texture scores were significantly better in the ergothioneine group.

Efficacy Guide:

1. Target Audience – Ergothioneine is a natural antioxidant ingredient and cell protector, considered very safe even for young children and pregnant women.

2. Gender – For women seeking good skin, ergothioneine is natural and gentle, capable of dispelling dullness and brightening complexion, not only delaying sagging but also making skin firmer, more elastic, tender, and hydrated. As a "longevity nutrient," ergothioneine helps men regulate immune cells and boost immunity, which aids in preventing and treating autoimmune diseases, infectious diseases, etc. It also has neuroprotective effects, offering potential help in preventing and treating neurodegenerative diseases like Parkinson's and Alzheimer's.

3. How to Obtain/Effects – Ergothioneine content in common foods is very low. The primary dietary source of ergothioneine for humans is mushrooms, with oyster mushrooms, morels, maitake, and shiitake containing the most. Relevant committees like the European Food Safety Authority have declared its safety, recommending a daily intake of ≤30mg for adults.

06 Spermidine: Induces Cellular Autophagy, Extends Lifespan

Spermidine is a polyamine naturally present in living organisms. Polyamines are organic compounds containing two or more amino groups that play crucial roles in cell growth, differentiation, and survival.

Spermidine shows surprising performance in anti-aging. Research has found that long-lived elderly individuals tend to have higher levels of spermidine in their bodies. In 2018, researchers selected 829 participants aged 45-84 and followed them for 20 years. They found that higher spermidine intake was associated with lower all-cause mortality, and long-term spermidine intake could extend lifespan by approximately 5.7 years.

Numerous studies indicate that while spermidine supports longevity through various different ways, its primary mechanism is autophagy. For example, a 2009 study showed that spermidine administration significantly extended the lifespan of yeast, flies, worms, and human immune cells. The researchers found that spermidine inhibited certain enzymes called acetyltransferases. These enzymes are related to DNA health. Consequently, gene expression involved in autophagy increased, thereby reducing cell death and extending lifespan.

Spermidine also plays a role in improving cognitive ability and preventing dementia. In 2021, a three-month spermidine intake study was conducted involving 85 subjects aged between 60 and 96 years in 6 nursing homes in Styria. The results indicated a clear correlation between spermidine intake and improved cognitive performance in patients with mild and moderate dementia who received the higher spermidine dose.

Efficacy Guide:

1. Target Audience – Middle-aged and Elderly: The rate of cellular aging accelerates. Spermidine's autophagy-promoting effect helps clear damaged organelles within cells, maintaining cellular health and thus delaying the aging process. Healthy Young People: The spermidine contained in a normal, balanced diet is generally sufficient (wheat germ, soybeans, and cruciferous vegetables are rich in spermidine). Additionally, individuals with long-term high-stress jobs and significant mental exertion can use spermidine supplements to help improve focus and energy.

2. Effects – In terms of effect manifestation, individuals with declining autophagy capacity or long-term exposure to pollutants may feel the effects of spermidine supplementation more quickly, reflected as a feeling of bodily lightness and increased energy.