Hallmarks of Ageing Targeted

• Epigenetic alterations
• Mitochondrial dysfunction
• Stem cell exhaustion
• Inflammaging
• Microbiome dysbiosis

Potential Benefits

• AKG influences multiple aging-related mechanisms, potentially prolonging lifespan. It regulates gene expression as well as inhibits mTOR and ATP synthase, which influences cell growth and metabolism [2].
• AKG seems to have a hormetic effect - by stimulating moderate production of reactive oxygen species, it promotes better functioning of defensive antioxidant mechanisms and increases general survival capacity [3].
• AKG serves as an important cofactor for several enzymes involved in protein metabolism, especially the production of collagen, which can potentially have a role in improving skin health [4].
• AKG is used to improve muscle protein synthesis, decrease muscle breakdown, and facilitate exercise recovery [5].
• As an antioxidant, AKG may help protect cells from oxidative stress [1].

Safety Considerations

AKG supplementation does not appear to cause any significant side effects. In a 3-year study of patients taking 4.5 grams of calcium AKG daily, no serious side effects were observed [6]. The adverse effects associated with the use of a combination of L-arginine and alpha-ketoglutarate were heart palpitations and dizziness [7], but those weren't reported when alpha-ketoglutarate was used alone.

Hallmarks of Ageing Targeted

• Genomic instability
• Epigenetic alterations
• Deregulated nutrient sensing
• Mitochondrial dysfunction
• Inflammaging

Potential Benefits

• CoQ10 supplementation has been shown to reduce oxidative stress, lower inflammation, and improve mitochondrial function [5].
• CoQ10 protects cell membranes from oxidative damage, decreasing markers of lipid peroxidation and protecting from several chronic health conditions [5].
• Clinical trials have shown that CoQ10 can effectively increase total antioxidant capacity and individual levels of key antioxidant enzymes in the body as well as reduce markers of oxidative stress [6].
• CoQ10 supplementation can decrease levels of inflammatory cytokines TNF-α and IL-6, higher levels of which are linked to chronic inflammation and aging [7], [8].
• CoQ10 may help combat mitochondrial dysfunction, one of the hallmarks of aging, which leads to errors in mitochondrial quality control mechanisms, resulting in decreased ATP production and increased generation of reactive oxygen species [9].
• Despite some paradoxical data in animals, the overall body of evidence from animal and human studies supports the beneficial effect of CoQ10 on increasing healthspan and preventing chronic disease [10].
• The influence of CoQ10 on longevity may be explained by its potential role in modulating sirtuin activity, which is tightly linked to the availability of NAD+ and CoQ10, both of which tend to decline with age [11].
• A recent clinical study showed that decreased cardiovascular mortality and reduced vascular aging can be explained by the effect of CoQ10 on SIRT1 activity [11].

Safety Considerations

Orally, coenzyme Q10 is generally well tolerated and no serious adverse effects have been reported in clinical studies. The most commonly reported adverse effects that occurred in less than 1% of patients include appetite suppression, diarrhea, epigastric discomfort, heartburn, nausea [12], [13], [14], [15]. However, most of these adverse effects can be minimized if daily doses above 100 mg are divided.

Hallmarks of Ageing Targeted

• Loss of proteostasis
• Deregulated nutrient sensing
• Mitochondrial dysfunction
• Inflammaging
• Disabled macroautophagy

Potential Benefits

• Research shows that creatine may positively affect muscle growth by stimulating muscle protein synthesis [1].
• Increased muscle mass improves metabolic health, particularly by acting as a buffer for glucose [2].
• Creatine greatly benefits muscle health, thus improving strength, fitness, and mobility [3].
• Paired with resistance training, creatine supplementation may improve bone health [4].
• Supplementing with creatine can improve cognitive functions in people with suboptimal creatine levels [5].
• Older adults and people following vegetarian/vegan diets may experience a more pronounced benefit as they typically have lower baseline levels of creatine [6], [7].

Safety Considerations

Creatine supplementation appears to be safe and well-tolerated up to 30 g/day for 5 years, let alone when used at maintenance doses of 4-5 grams daily. Moreover, significant benefits may be provided by ensuring habitual low dietary creatine ingestion, such as 3 grams daily [8]. High-quality clinical research shows that creatine does not increase the incidence of gastrointestinal adverse effects. Nevertheless, creatine may cause dehydration, diarrhea, gastrointestinal upset, muscle cramps, and water retention in some individuals, but it's highly unlikely to occur at maintenance doses of 3-5 grams/day [8], [9], [10].

Hallmarks of Ageing Targeted

• Genomic instability
• Loss of proteostasis
• Mitochondrial dysfunction

Potential Benefits

• Glucosamine sulfate has anti-inflammatory properties and can inhibit pro-inflammatory cytokines such as interleukin-1 (IL-1) [1].
• A meta-analysis of randomized clinical trials found that glucosamine sulfate may reduce joint pain and prevent narrowing of joint spaces and cartilage loss [2], [3].
• Long-term supplementation with glucosamine sulfate has been shown to decrease the risk of developing radiographic knee osteoarthritis over 2.5 years [4].
• A recent prospective study found that regular glucosamine use is associated with a lower risk for total mortality (15%), CVD mortality (18%), cancer mortality (6%), respiratory mortality (27%) and digestive mortality (26%) [5].
• Glucosamine sulfate is thought to mimic the effects of calorie restriction [6].
• It protects from DNA damage, lowers chronic inflammation, and may promote better mitochondrial function, targeting several hallmarks of aging [7], [8].
• Glucosamine may reduce wrinkles and improve skin health due to its effect on inhibiting metalloproteinases that cause degradation of collagen and elastin fibers in the skin [9], [10], [11].

Safety Considerations

Orally, glucosamine sulfate seems to be well tolerated. Glucosamine sulfate has been used safely in multiple clinical trials at a dose of 1000-1500 mg daily for up to 3 years [12], [13], [14]. Although quite rare, the most common side effects include bloating, constipation, stomach cramps, diarrhea, heartburn, and nausea.

Hallmarks of Ageing Targeted

• Epigenetic alterations
• Deregulated nutrient sensing
• Mitochondrial dysfunction
• Altered cellular communication
• Inflammaging
• Microbiome dysbiosis

Potential Benefits

• Green tea catechins, including epigallocatechin gallate (EGCG), can increase lifespan in model organisms by improving mitochondrial function and reducing oxidative stress [2].
• EGCG can inhibit complex I of the mitochondrial electron transport chain, thus reducing production of reactive oxygen species (ROS) [2].
• Green tea polyphenols can induce mitophagy, a process of clearing up damaged and dysfunctional mitochondria, which is thought to be an important anti-aging mechanism [3].
• Consumption of green tea is associated with reduced mortality from cardiovascular and other age-related conditions [4], [5].
• Green tea extract improves glycemic control, according to recent meta-analyses of randomized clinical trials [6].
• Green tea extract improves lipid profile, as shown in meta-analyses of randomized clinical trials [7].

Safety Considerations

According to clinical trials, green tea extract seems to be well tolerated when used in clinical trials for up to 12 months. Green tea extract might cause bloating, constipation, diarrhea, dyspepsia, flatulence, and nausea, but these effects are most common when the amount of green tea extract is equivalent to 5-6 liters of tea per day [8], [9], [10].

Hallmarks of Ageing Targeted

• Epigenetic alterations
• Loss of proteostasis
• Deregulated nutrient sensing
• Mitochondrial dysfunction
• Stem cell exhaustion
• Inflammaging
• Disabled macroautophagy
• Microbiome dysbiosis

Potential Benefits

• Some pro-longevity properties of glycine are tied to an enzyme called glycine-N-methyltransferase (GNMT), which is important for methionine clearance, and methionine restriction is one of the anti-aging mechanisms [1].
• Glycine can induce autophagy, a cellular process important for longevity [1].
• Glycine is a well-known sleep aid as it can improve sleep quality, which is a crucial component of longevity [2], [3].
• Glycine reduces inflammation and oxidative stress [4], [5].
• Glycine reduces the formation of advanced glycation end products (AGEs), which are involved in accelerated aging [6], [7].

Safety Considerations

Orally, glycine seems to be well tolerated, and doses up to 9 grams/day rarely cause side effects, such as nausea, soft stools, and mild sedative effect [8], [9], [10].

Hallmarks of Ageing Targeted

• Loss of proteostasis
• Deregulated nutrient sensing
• Mitochondrial dysfunction
• Altered cellular communication

Potential Benefits

• The bioactive compounds of the mushroom stimulate the synthesis of nerve growth factor (NGF) in astrocytes in the hippocampus, improving proliferation and differentiation of neuronal cells [1].
• Higher NGF levels have been associated with improved neurogenesis and better neuroplasticity, playing a role in prevention of neurodegenerative conditions [2].
• Lion's mane can reduce oxidative damage in hippocampal neurons and microglial cells, strengthening the evidence behind the mushroom's cognitive benefits [3].
• In clinical trials, supplementation with lion's mane has been shown to improve cognitive function [4], [5].
• Lion's mane supplementation has been shown to reduce symptoms of anxiety and depression [6].
• Lion's mane also has an anti-inflammatory effect, but evidence is still limited to cell and animal models [7], [8].

Safety Considerations

Supplementation with lion's mane rarely causes significant adverse effects. Some of the most common side effects previously noted by participants of clinical studies include nausea, gastrointestinal discomfort, diarrhea, and skin rash. [9], [10].

Hallmarks of Ageing Targeted

• Genomic instability
• Telomere attrition
• Deregulated nutrient sensing
• Mitochondrial dysfunction
• Altered cellular communication
• Inflammaging

Magnesium Taurate

• Magnesium taurate combines magnesium with taurine, an amino acid.
• Taurine is particularly important for electrically active organs and tissues, like heart, skeletal muscle, brain, and retina [7].
• It's especially useful for stabilization of cell membranes and their protection from oxidative damage [7].
• Taurine is often used in treatment of cardiovascular, neurodegenerative, and muscle diseases [8].

Potential Benefits

• Adequate magnesium levels help prevent cardiovascular disease [3].
• Magnesium plays a role in preventing inflammatory disorders [4].
• Magnesium may increase testosterone levels [5].
• The formula provides two highly bioavailable forms of magnesium: malate and taurate [6].

Safety Considerations

Although rare, doses greater than 350 mg daily may cause loose stools and diarrhea in sensitive individuals [9]. However, such effects are more applicable to magnesium citrate and magnesium oxide.

Hallmarks of Ageing Targeted

• Genomic instability
• Telomere attrition
• Deregulated nutrient sensing
• Mitochondrial dysfunction
• Altered cellular communication
• Inflammaging

Magnesium Malate

• Magnesium malate combines magnesium with malic acid.
• It is often used for addressing issues like chronic pain, muscle weakness, low energy, and heart issues due to the role of malic acid in the energy metabolism of a cell [6].

Potential Benefits

• Adequate magnesium levels help prevent cardiovascular disease [3].
• Magnesium plays a role in preventing inflammatory disorders [4].
• Magnesium may increase testosterone levels [5].
• The formula provides two highly bioavailable forms of magnesium: malate and taurate [6].

Safety Considerations

Although rare, doses greater than 350 mg daily may cause loose stools and diarrhea in sensitive individuals [7]. However, such effects are more applicable to magnesium citrate and magnesium oxide.

Hallmarks of Ageing Targeted

• Genomic instability
• Epigenetic alterations
• Loss of proteostasis
• Deregulated nutrient sensing
• Mitochondrial dysfunction
• Cellular senescence
• Altered cellular communication
• Inflammaging
• Disabled macroautophagy
• Microbiome dysbiosis

Potential Benefits

• The pro-longevity effect of quercetin can be mediated by its influence on genes that control carbohydrate, lipid, and energy metabolism [1].
• It can activate the AMPK-SIRT1 pathway and inhibit NF-κB pathway, thus influencing cellular energy metabolism and stress responses as well as exhibiting anti-inflammatory effects [2], [3].
• Targeting proAMPK-SIRT1 may promote longevity by improving mitochondrial function and reducing cellular senescence on one hand and promoting cellular senescence in cancer cells on the other [2], [3].
• According to clinical studies, quercetin has a positive impact on glucose metabolism [4], [5].
• Quercetin can improve lipid profile [4], [7].
• It can reduce blood pressure, supporting its role in prevention of age-related diseases [4], [6].

Safety Considerations

Quercetin appears to be very safe and no side effects have been recorded in doses of a few grams per day.

Hallmarks of Ageing Targeted

• Genomic instability
• Epigenetic alterations
• Deregulated nutrient sensing

Potential Benefits

• TMG helps metabolize homocysteine, playing a role in cardiovascular health [1], [2].
• It indirectly increases the levels of folate and S-adenosylmethionine (SAMe), the main methyl donors in the body [3].
• Folate and SAMe methylate DNA, which is the primary process of turning genes on and off [3].
• Methylation is crucial for maintaining genomic stability and regulating gene expression, whose dysfunction is one of the hallmarks of aging [3].
• TMG acts as an osmolyte: increasing TMG's intracellular concentrations improves cell hydration and resilience to stress factors [4].

Safety Considerations

Trimethylglycine is very safe. Mild gastrointestinal side effects, such as nausea, diarrhea, or stomach upset, may occur at doses up to 6 grams per day [5], [6].