The Power of Sirtuins in Unlocking Longevity and Reversing Aging
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Sirtuins are a family of longevity genes that play a crucial role in regulating longevity as well as cell response to stressors, like oxidative stress. These powerful enzymes have been the subject of extensive research in recent years, and it seems that switching them on, along with good nutrition, regular exercise and a supplement regimen, can enhance both your healthspan and lifespan. So how exactly do these genes combat aging?
Bit of a breakdown for you...
Diet and Your Genes
Top longevity scientists, (you may have heard of Harvard’s Professor David Sinclair), have discovered that part of the challenge with the aging process, is the gradual unraveling of DNA, leading to the activation of genes that should remain dormant. Like sirtuins, two other key longevity genes, mTOR and AMPK also need to be kept in check. But the good news is, you can manipulate the behaviour of these important genes, simply by changing your eating habits .
Here’s a brief rundown of these 3 key genes…
How to Stimulate your Sirtuins
One of the major roles of sirtuins is their ability to regulate gene expression, repair damaged DNA and keep cells healthy. Stress on the body such as caloric restriction, intermittent fasting and exercising can spur these genes into activity. But if you are not particularly fond of fasting, you’re in luck because researchers have found that specific compounds, like NAD, NR, NMN (check out previous blogs on these supplements) as well as resveratrol, a polyphenol in red wine, can also stimulate these critical proteins. Studies have shown that by taking care of these genes through diet, supplements, and exercise, not only can we slow the aging process, but even improve age-related diseases like cancer, Alzheimer's, and diabetes. So putting your body through a little adversity can actually be good for you. This adaptive response of the body, where a little stress creates resilience, but too much is detrimental, is known as a ‘hormetic response’, or ‘hormesis’. We see this adaptive response in the plant world as well, so no need to throw out your wilting herbs or veggies, because it’s at this stage that they are manufacturing their most potent phytochemicals!
Switch off your mTOR Genes
When you consume a high protein meal, the mTOR gene (a.k.a the 'Mammalian Target of Rapamycin' gene) is switched on. This gene decides how much protein your body makes, as well as how your cells grow, and divide, and how long they stay alive. So essentially when you eat a lot of protein, mTOR is activated and you build up muscle, which is great for your body, right? Not really. Turns out, although your body needs an adequate amount of muscle tissue, over-stimulating the mTOR gene is actually linked to age related conditions like cancer and diabetes. Slowing this gene’s activity is the key to maintaining long-term health, largely because it stimulates a cell recycling process, known as ‘autophagy’, (from the Greek word ‘phagy’ meaning to eat, and ‘auto’ meaning self). This cellular clean-up procedure improves cell function and overall performance and can ultimately extend your health-span.
Up-regulate your AMPK Enzymes
The AMPK enzyme (a.k.a Adenosine 5’ Monophosphate-activated Protein Kinase) plays a crucial role in regulating energy. As we age we tend to lose mitochondria, and we need these little powerhouses to turn our food into energy in the cell. When AMPK is activated, it up-regulates mitochondria, and increases energy levels. Poor mitochondrial functioning has been linked to heart disease, dementia, type 2 diabetes, metabolic syndrome, and insulin resistance, so active, healthy mitochondria are crucial for health
AMPK also plays a central role in the body's defense system, and is a key regulator of major genes like mTOR and other longevity genes that promotes overall health. It’s also involved with blood sugar, and when our cells are glucose deprived like during fasting, AMPK is triggered. For the non-fasters, this enzyme can also be up-regulated by taking certain natural supplements like Berberine, which can lower blood sugar levels and improve insulin sensitivity.
Can your Skincare Combat Aging?
Your skin is your largest detoxification organ, along with your liver, kidneys and lungs. Taking care of your skin with healthy routines like regular skin brushing, maintaining adequate hydration as well as responsible sun exposure will help maintain the integrity of this multifunctional organ. Watching what you slather all over your skin, can also play a big factor in your overall health, and choosing clean products that don’t add to the elimination burden on your body can go a long way towards improving your health. We only use responsibly sourced, clean, organic ingredients in our skincare line, as well as many of the supplements mentioned here in this article. Studies into topical application of these ingredients are growing, particularly resveratrol which has a long history of promising research, since it was first discovered in france that vineyard workers age spots disappeared over time working with grapes
The Power of Sirtuins in Unlocking Longevity and Reversing Aging
By unraveling the mysteries of these fascinating proteins, researchers hope to develop novel therapies to combat age related conditions and extend our life and healthspan. But what can we do? Lifestyle choices like choosing clean personal care products, exercise, fasting, limiting protein intake, increasing plant-based foods, supplementing where necessary, as well as stress management and adequate sleep will all help naturally boost sirtuins and improve your longevity.
Overall, the discovery of sirtuins is a significant breakthrough in the field of longevity and health research. The potential applications for improving human health and extending lifespan have become more promising than ever before.
References:
1. Lin SJ, Defossez PA, Guarente L. Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science. 2000;289:2126–2128.
2. Grozio A, et al. CD73 protein as a source of extracellular precursors for sustained NAD+ biosynthesis in FK866-treated tumor cells. J Biol Chem. 2013;288:25938–25949.
3. Scheibye-Knudsen M, et al. A high-fat diet and NAD+ activate Sirt1 to rescue premature aging in cockayne syndrome. Cell Metab. 2014;20:840–855.
4. Brown KD, et al. Activation of SIRT3 by the NAD+ precursor nicotinamide riboside protects from noise-induced hearing loss. Cell Metab. 2014;20:1059–1068.
5. Yang H, et al. Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival. Cell. 2007;130:1095–1107.
6. Mouchiroud L, et al. The NAD+/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell. 2013;154:430–441.
7. Canto C, et al. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature. 2009;458:1056–1060.
8. Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Sinclair DA. Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. Nature. 2003;423:181–185.
9. Imai S, Armstrong CM, Kaeberlein M, Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000;403:795–800. The first study to determine the mechanism for Sir2 was a NAD-dependent histone deacetylase.
10. Landry J, et al. The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases. Proc Natl Acad Sci USA. 2000;97:5807–5811.
11. Schmeisser K, et al. Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide. Nat Chem Biol. 2013;9:693–700.
12. Moroz N, et al. Dietary restriction involves NAD+-dependent mechanisms and a shift toward oxidative metabolism. Aging Cell. 2014;13:1075–1085.
13. Vaziri H, et al. hSIR2SIRT1 functions as an NAD-dependent p53 deacetylase. Cell. 2001;107:149–159.
14. Du J, et al. Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science. 2011;334:806–809.
15. Feldman JL, et al. Kinetic and structural basis for acyl-group selectivity and NAD dependence in sirtuin-catalyzed deacylation. Biochemistry. 2015;54:3037–3050.
16. Bitterman KJ, Anderson RM, Cohen HY, Latorre-Esteves M, Sinclair DA. Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1. J Biol Chem. 2002;277:45099–45107.
17. Landry J, Slama JT, Sternglanz R. Role of NAD+ in the deacetylase activity of the SIR2-like proteins. Biochem Biophys Res Commun. 2000;278:685–690.
18. Kraus D, et al. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature. 2014;508:258–262.
19. Hong S, et al. Nicotinamide N-methyltransferase regulates hepatic nutrient metabolism through Sirt1 protein stabilization. Nat Med. 2015;21:887–894.
20. Mouchiroud L, et al. The NAD+/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell. 2013;154:430–441.
21. Janson M. Orthomolecular medicine: The therapeutic use of dietary supplements for anti-aging. Clin. Interv. Aging. 2006;1:261–265. doi: 10.2147/ciia.2006.1.3.261.
22. Sirtuins in Skin and Skin Cancers. Garcia-Peterson LM, Wilking-Busch MJ, Ndiaye MA, Philippe CGA, Setaluri V, Ahmad N.Skin Pharmacol Physiol. 2017;30(4):216-224. doi: 10.1159/000477417. Epub 2017 Jul 14.PMID: 28704830
23. Carafa V, et al. Sirtuin functions and modulation: from chemistry to the clinic. Clin Epigenetics. 2016;8:61. An in-depth review discussing sirtuin inhibition as a potential therapeutic target.
24. Imai S, Armstrong CM, Kaeberlein M, Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000;403:795–800.
Bit of a breakdown for you...
Diet and Your Genes
Top longevity scientists, (you may have heard of Harvard’s Professor David Sinclair), have discovered that part of the challenge with the aging process, is the gradual unraveling of DNA, leading to the activation of genes that should remain dormant. Like sirtuins, two other key longevity genes, mTOR and AMPK also need to be kept in check. But the good news is, you can manipulate the behaviour of these important genes, simply by changing your eating habits .
Here’s a brief rundown of these 3 key genes…
How to Stimulate your Sirtuins
One of the major roles of sirtuins is their ability to regulate gene expression, repair damaged DNA and keep cells healthy. Stress on the body such as caloric restriction, intermittent fasting and exercising can spur these genes into activity. But if you are not particularly fond of fasting, you’re in luck because researchers have found that specific compounds, like NAD, NR, NMN (check out previous blogs on these supplements) as well as resveratrol, a polyphenol in red wine, can also stimulate these critical proteins. Studies have shown that by taking care of these genes through diet, supplements, and exercise, not only can we slow the aging process, but even improve age-related diseases like cancer, Alzheimer's, and diabetes. So putting your body through a little adversity can actually be good for you. This adaptive response of the body, where a little stress creates resilience, but too much is detrimental, is known as a ‘hormetic response’, or ‘hormesis’. We see this adaptive response in the plant world as well, so no need to throw out your wilting herbs or veggies, because it’s at this stage that they are manufacturing their most potent phytochemicals!
Switch off your mTOR Genes
When you consume a high protein meal, the mTOR gene (a.k.a the 'Mammalian Target of Rapamycin' gene) is switched on. This gene decides how much protein your body makes, as well as how your cells grow, and divide, and how long they stay alive. So essentially when you eat a lot of protein, mTOR is activated and you build up muscle, which is great for your body, right? Not really. Turns out, although your body needs an adequate amount of muscle tissue, over-stimulating the mTOR gene is actually linked to age related conditions like cancer and diabetes. Slowing this gene’s activity is the key to maintaining long-term health, largely because it stimulates a cell recycling process, known as ‘autophagy’, (from the Greek word ‘phagy’ meaning to eat, and ‘auto’ meaning self). This cellular clean-up procedure improves cell function and overall performance and can ultimately extend your health-span.
Up-regulate your AMPK Enzymes
The AMPK enzyme (a.k.a Adenosine 5’ Monophosphate-activated Protein Kinase) plays a crucial role in regulating energy. As we age we tend to lose mitochondria, and we need these little powerhouses to turn our food into energy in the cell. When AMPK is activated, it up-regulates mitochondria, and increases energy levels. Poor mitochondrial functioning has been linked to heart disease, dementia, type 2 diabetes, metabolic syndrome, and insulin resistance, so active, healthy mitochondria are crucial for health
AMPK also plays a central role in the body's defense system, and is a key regulator of major genes like mTOR and other longevity genes that promotes overall health. It’s also involved with blood sugar, and when our cells are glucose deprived like during fasting, AMPK is triggered. For the non-fasters, this enzyme can also be up-regulated by taking certain natural supplements like Berberine, which can lower blood sugar levels and improve insulin sensitivity.
Can your Skincare Combat Aging?
Your skin is your largest detoxification organ, along with your liver, kidneys and lungs. Taking care of your skin with healthy routines like regular skin brushing, maintaining adequate hydration as well as responsible sun exposure will help maintain the integrity of this multifunctional organ. Watching what you slather all over your skin, can also play a big factor in your overall health, and choosing clean products that don’t add to the elimination burden on your body can go a long way towards improving your health. We only use responsibly sourced, clean, organic ingredients in our skincare line, as well as many of the supplements mentioned here in this article. Studies into topical application of these ingredients are growing, particularly resveratrol which has a long history of promising research, since it was first discovered in france that vineyard workers age spots disappeared over time working with grapes
The Power of Sirtuins in Unlocking Longevity and Reversing Aging
By unraveling the mysteries of these fascinating proteins, researchers hope to develop novel therapies to combat age related conditions and extend our life and healthspan. But what can we do? Lifestyle choices like choosing clean personal care products, exercise, fasting, limiting protein intake, increasing plant-based foods, supplementing where necessary, as well as stress management and adequate sleep will all help naturally boost sirtuins and improve your longevity.
Overall, the discovery of sirtuins is a significant breakthrough in the field of longevity and health research. The potential applications for improving human health and extending lifespan have become more promising than ever before.
References:
1. Lin SJ, Defossez PA, Guarente L. Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science. 2000;289:2126–2128.
2. Grozio A, et al. CD73 protein as a source of extracellular precursors for sustained NAD+ biosynthesis in FK866-treated tumor cells. J Biol Chem. 2013;288:25938–25949.
3. Scheibye-Knudsen M, et al. A high-fat diet and NAD+ activate Sirt1 to rescue premature aging in cockayne syndrome. Cell Metab. 2014;20:840–855.
4. Brown KD, et al. Activation of SIRT3 by the NAD+ precursor nicotinamide riboside protects from noise-induced hearing loss. Cell Metab. 2014;20:1059–1068.
5. Yang H, et al. Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival. Cell. 2007;130:1095–1107.
6. Mouchiroud L, et al. The NAD+/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell. 2013;154:430–441.
7. Canto C, et al. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature. 2009;458:1056–1060.
8. Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Sinclair DA. Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. Nature. 2003;423:181–185.
9. Imai S, Armstrong CM, Kaeberlein M, Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000;403:795–800. The first study to determine the mechanism for Sir2 was a NAD-dependent histone deacetylase.
10. Landry J, et al. The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases. Proc Natl Acad Sci USA. 2000;97:5807–5811.
11. Schmeisser K, et al. Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide. Nat Chem Biol. 2013;9:693–700.
12. Moroz N, et al. Dietary restriction involves NAD+-dependent mechanisms and a shift toward oxidative metabolism. Aging Cell. 2014;13:1075–1085.
13. Vaziri H, et al. hSIR2SIRT1 functions as an NAD-dependent p53 deacetylase. Cell. 2001;107:149–159.
14. Du J, et al. Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science. 2011;334:806–809.
15. Feldman JL, et al. Kinetic and structural basis for acyl-group selectivity and NAD dependence in sirtuin-catalyzed deacylation. Biochemistry. 2015;54:3037–3050.
16. Bitterman KJ, Anderson RM, Cohen HY, Latorre-Esteves M, Sinclair DA. Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1. J Biol Chem. 2002;277:45099–45107.
17. Landry J, Slama JT, Sternglanz R. Role of NAD+ in the deacetylase activity of the SIR2-like proteins. Biochem Biophys Res Commun. 2000;278:685–690.
18. Kraus D, et al. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature. 2014;508:258–262.
19. Hong S, et al. Nicotinamide N-methyltransferase regulates hepatic nutrient metabolism through Sirt1 protein stabilization. Nat Med. 2015;21:887–894.
20. Mouchiroud L, et al. The NAD+/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell. 2013;154:430–441.
21. Janson M. Orthomolecular medicine: The therapeutic use of dietary supplements for anti-aging. Clin. Interv. Aging. 2006;1:261–265. doi: 10.2147/ciia.2006.1.3.261.
22. Sirtuins in Skin and Skin Cancers. Garcia-Peterson LM, Wilking-Busch MJ, Ndiaye MA, Philippe CGA, Setaluri V, Ahmad N.Skin Pharmacol Physiol. 2017;30(4):216-224. doi: 10.1159/000477417. Epub 2017 Jul 14.PMID: 28704830
23. Carafa V, et al. Sirtuin functions and modulation: from chemistry to the clinic. Clin Epigenetics. 2016;8:61. An in-depth review discussing sirtuin inhibition as a potential therapeutic target.
24. Imai S, Armstrong CM, Kaeberlein M, Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000;403:795–800.
