Micronutrients and aging

There is growing interest in the potential for certain vitamins and nutrients to slow down aging by affecting the hallmarks of aging, such as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication.

Here are some examples of nutrients and their effects:

Vitamin D

Vitamin D has been shown to play a role in regulating the immune system, maintaining bone health, and reducing inflammation. In a study of older adults, higher levels of vitamin D were associated with longer telomeres, a marker of cellular aging. Additionally, vitamin D has been shown to improve mitochondrial function and protect against oxidative stress, which can contribute to cellular damage and aging(1).

Omega-3 Fatty acids

Omega-3 fatty acids are essential fatty acids that are found in fatty fish, such as salmon and tuna, as well as in plant sources like flaxseeds and chia seeds. Omega-3s have been shown to reduce inflammation, improve cardiovascular health, and protect against age-related cognitive decline. Additionally, omega-3s may help to maintain telomere length and protect against oxidative stress(2).

Vitamin E

Vitamin E is a fat-soluble vitamin that acts as an antioxidant in the body. Vitamin E has been shown to protect against oxidative stress, reduce inflammation, and improve immune function. Additionally, vitamin E may help to prevent telomere shortening and protect against age-related cognitive decline(3).

Magnesium

Magnesium is an essential mineral that plays a role in many biological processes, including energy metabolism, protein synthesis, and DNA repair. Magnesium has been shown to improve mitochondrial function and reduce oxidative stress, which can contribute to cellular damage and aging. Additionally, magnesium may help to regulate cellular signaling pathways involved in cellular senescence and inflammation(4).

Zinc

Zinc is an essential mineral that is involved in many biological processes, including immune function, DNA synthesis, and wound healing. Zinc has been shown to protect against oxidative stress and inflammation, which can contribute to cellular damage and aging. Additionally, zinc may help to regulate cellular signaling pathways involved in cellular senescence and apoptosis(5).

Folate

Folate is a B-vitamin that is important for DNA synthesis and repair, as well as for maintaining healthy red blood cells. Folate has been shown to regulate gene expression and cellular signaling pathways involved in cellular senescence and apoptosis. Additionally, folate may help to reduce inflammation and oxidative stress, which can contribute to cellular damage and aging(6).

Vitamin B12

Vitamin B12 is a water-soluble vitamin that is essential for DNA synthesis and nerve function. Vitamin B12 deficiency can lead to anemia and nerve damage. Vitamin B12 has been shown to protect against oxidative stress and inflammation, which can contribute to cellular damage and aging. Additionally, vitamin B12 may help to regulate cellular signaling pathways involved in cellular senescence and apoptosis(7).

Vitamin A

Vitamin A is a fat-soluble vitamin that is important for vision, immune function, and cell growth and differentiation. Vitamin A has been shown to regulate gene expression and cellular signaling pathways involved in cellular senescence and apoptosis. Additionally, vitamin A may help to reduce inflammation and oxidative stress, which can contribute to cellular damage and aging(8).

Vitamin B1

Vitamin B1, also known as thiamin, is a water-soluble vitamin that is important for energy metabolism and nerve function. Vitamin B1 deficiency can lead to neurological symptoms and cognitive impairment. Vitamin B1 has been shown to regulate cellular signaling pathways involved in cellular senescence and apoptosis. Additionally, vitamin B1 may help to reduce inflammation and oxidative stress, which can contribute to cellular damage and aging(9).

Vitamin B2 (Riboflavin)

Vitamin B2, also known as riboflavin, is a water-soluble vitamin that is important for energy metabolism and antioxidant defense. Vitamin B2 deficiency can lead to anemia and skin disorders. Vitamin B2 has been shown to protect against oxidative stress and reduce inflammation, which can contribute to cellular damage and aging(10).

Vitamin B3 (niacin)

Vitamin B3, also known as niacin, is a water-soluble vitamin that is important for energy metabolism and DNA repair. Vitamin B3 has been shown to protect against oxidative stress and reduce inflammation, which can contribute to cellular damage and aging. Additionally, vitamin B3 may help to regulate cellular signaling pathways involved in cellular senescence and apoptosis(11).

Iodine

Iodine is an essential mineral that is important for thyroid function and the production of thyroid hormones. Iodine deficiency can lead to goiter and hypothyroidism. Iodine has been shown to protect against oxidative stress and reduce inflammation, which can contribute to cellular damage and aging(12).

Lesser known micronutrients

Metformin, NMN, rapamycin, spermidine, vitamin K, TMG, resveratrol (or pterostilbene) have all been studied for their potential anti-aging effects. These supplements have been shown to target various hallmarks of aging, which are the nine biological processes that are thought to contribute to aging.

Metformin has been found to activate AMPK, a protein that plays a key role in cellular energy metabolism. This can improve insulin sensitivity, reduce inflammation, and reduce the risk of certain age-related diseases such as cardiovascular disease and cancer.

NMN and rapamycin have been shown to increase levels of NAD+ and inhibit mTOR, respectively. These actions can improve metabolic function and help to prevent age-related diseases.

Spermidine has been found to promote autophagy, a process by which the body cleans up damaged cells and debris, which may help to slow down the aging process.

Vitamin K2 has been shown to help prevent the calcification of arteries and improve bone density, which can help to reduce the risk of age-related diseases.

TMG has been found to increase levels of SAMe, a compound that is involved in a range of cellular processes and may have anti-aging effects.

Resveratrol and pterostilbene have been found to have potential anti-aging effects, including reducing inflammation, improving heart health, and promoting healthy brain function. In addition, resveratrol has been found to activate sirtuins, a group of proteins that are involved in regulating cellular metabolism and may play a role in the aging process.

Metformin

Metformin is an oral medication commonly used to treat type 2 diabetes. It works by reducing glucose production in the liver and improving insulin sensitivity, which helps to lower blood sugar levels. However, recent research has shown that metformin may also have anti-aging properties and could potentially help to prevent age-related diseases(15).

Metformin has been found to activate AMP-activated protein kinase (AMPK), a protein that plays a key role in cellular energy metabolism. This can improve insulin sensitivity, reduce inflammation, and reduce the risk of certain age-related diseases such as cardiovascular disease and cancer. In addition, metformin has been shown to reduce the risk of cognitive decline and may have neuroprotective effects(16).

Several studies have investigated the potential anti-aging effects of metformin. One study found that metformin extended the lifespan of nematode worms by increasing their resistance to oxidative stress(17). Another study found that metformin treatment in mice resulted in improved insulin sensitivity, reduced inflammation, and a reduction in age-related diseases such as cancer and heart disease(18).

A clinical trial called the Targeting Aging with Metformin (TAME) trial is currently underway to investigate whether metformin can extend the lifespan of humans. The trial aims to enroll 3,000 elderly adults with or without diabetes and evaluate the effects of metformin on a range of age-related diseases(19).

Resveratrol (or pterostilbene)

Resveratrol is a polyphenol found in red grapes, peanuts, and berries that has been shown to have anti-inflammatory and antioxidant effects. Resveratrol has been found to activate sirtuins, which are enzymes that play a role in regulating gene expression and cellular aging. Additionally, resveratrol may help to protect against mitochondrial dysfunction and cellular senescence(13).

In a study published in the journal Cell Metabolism, resveratrol was found to improve glucose metabolism and insulin sensitivity in obese humans(14).

Resveratrol and pterostilbene have been found to have potential anti-aging effects, including reducing inflammation, improving heart health, and promoting healthy brain function. In addition, resveratrol has been found to activate sirtuins, a group of proteins that are involved in regulating cellular metabolism and may play a role in the aging process(20,21).

Studies have shown that resveratrol and pterostilbene can improve heart health by reducing inflammation, lowering blood pressure, and improving cholesterol levels. Resveratrol has also been found to improve insulin sensitivity and reduce the risk of developing type 2 diabetes(22).

Resveratrol and pterostilbene have also been found to have neuroprotective effects and may help to prevent age-related cognitive decline. Resveratrol has been shown to improve memory and cognitive function in older adults, while pterostilbene has been found to protect against neurotoxicity in animal studies(24,25,26).

NMN

NMN (nicotinamide mononucleotide) is a compound that is naturally produced in the body and is involved in cellular energy metabolism. It is a precursor to NAD+ (nicotinamide adenine dinucleotide), a molecule that is important for cellular metabolism and has been shown to decline with age(27).

Studies have shown that NMN supplementation can increase levels of NAD+ and improve metabolic function(28). NMN has also been found to improve glucose tolerance, reduce inflammation, and improve cognitive function in animal studies(29).

NMN may also have anti-aging effects, including improving mitochondrial function and promoting healthy aging. One study found that NMN supplementation in mice resulted in improved glucose metabolism, reduced body weight, and increased physical activity(30). Another study found that NMN supplementation increased lifespan and reduced age-related symptoms in mice(31).

Spermidine

Spermidine is a polyamine compound that is found in foods such as cheese, soybeans, and wheat germ. It has been found to have potential anti-aging effects, including promoting autophagy, reducing inflammation, and improving cardiovascular health(32).

Autophagy is a cellular process in which damaged or unnecessary cellular components are broken down and recycled. Spermidine has been found to induce autophagy and may help to prevent age-related diseases such as neurodegenerative diseases and cancer(33,34).

Studies have also shown that spermidine can reduce inflammation and improve cardiovascular health. One study found that spermidine supplementation in mice resulted in reduced arterial stiffness, improved blood flow, and increased lifespan(35). Another study found that spermidine supplementation in human participants improved markers of cardiovascular health such as blood pressure and cholesterol levels(36).

Vitamin K

Vitamin K is a fat-soluble vitamin that is important for blood clotting and bone health. There are two main forms of vitamin K: vitamin K1 (phylloquinone), which is found in green leafy vegetables, and vitamin K2 (menaquinone), which is found in fermented foods and animal products.

Recent research has suggested that vitamin K2 may have potential anti-aging effects, including reducing inflammation, promoting bone health, and improving cardiovascular health. Vitamin K2 has also been found to activate proteins involved in cellular metabolism, which may play a role in the aging process(40,41).

Studies have shown that vitamin K2 supplementation can improve bone density and reduce the risk of fractures in postmenopausal women (37). In addition, vitamin K2 has been found to reduce arterial stiffness and improve cardiovascular health in healthy postmenopausal women (38).

Vitamin K2 may also have anti-inflammatory effects, which could help to reduce the risk of age-related diseases such as Alzheimer’s disease and cancer. One study found that vitamin K2 supplementation reduced levels of a biomarker for inflammation in postmenopausal women (39).

TMG (trimethylglycine or betaine)

TMG is a compound that is naturally found in beets, spinach, and other vegetables. It is also available as a dietary supplement. TMG has been found to have potential anti-aging effects, including reducing inflammation, improving cardiovascular health, and promoting healthy liver function(45,46).

One of the key ways in which TMG may promote healthy aging is by reducing levels of homocysteine, an amino acid that is associated with inflammation and an increased risk of cardiovascular disease. Studies have shown that TMG supplementation can lower levels of homocysteine in healthy adults (42).

TMG may also have liver-protective effects and can improve liver function in people with non-alcoholic fatty liver disease (NAFLD) (43). In addition, TMG has been found to reduce oxidative stress and inflammation in animal studies, which could help to prevent age-related diseases such as Alzheimer’s disease (44).

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