Sirtuins: Benefits and How to Activate Them (2023)

The sirtuin system consists of seven regulatory enzymes responsible for metabolism, antioxidant protection, and cell cycle regulation. The great interest in sirtuins is associated with the potential impact on life extension.

In this article, you will learn what sirtuins are. You will understand how sirtuins impact mitochondria and aging. You will understand the benefits and drawbacks of sirtuins. I will share my top natural strategies to activate the healthy expression of sirtuins.

What Are Sirtuins

Sirtuins are a family of proteins. They serve as metabolic sensors and help to regulate cellular homeostasis and cellular health.   Sirtuins are only able to function with the help of nicotinamide adenine dinucleotide, or NAD+.

NAD+ is a coenzyme located in all your living cells and is essential to cellular metabolism and a list of other important biological processes.  They break down acetyl from NAD+ to make free nicotinamide, or NADH to allow it to function for a longer time. In a healthy body, there needs to be a balance between the oxidized and reduced forms of nicotinamide, referred to as the NAD+/NADH ratio. This ratio provides a clue to the nutritional status of each cell so sirtuins know what to do to achieve balance. 

NAD+ is necessary for both energy metabolism and DNA repair and sirtuins are there to make sure that there are enough NAD+ coenzymes available in your body. According to research, including a 2013 study published in the Journal of Leukocyte Biology and a 2010 study published in the Journal of Neuroscience, sirtuins help to regulate inflammation, immune response, DNA transcription, apoptosis, aging, and reaction to caloric restriction (1, 2).

Sirtuins also play an important role in mitochondrial biogenesis, circadian rhythms, and cellular stress response to both oxidative and genotoxic stress. In a healthy body, sirtuins help to keep your body healthy and support a long lifespan.

How Sirtuins Impact Mitochondria and Aging

Sirtuins can have a serious impact on both mitochondrial health and aging. They can help to increase longevity, cellular autophagy, and mitochondrial function. A 1999 study published in Genes Development has discovered the overexpression of the SIRT2 gene in yeast can increase lifespan by 70 percent (3). According to a 2007 review published in Cold Spring Harbor Symposia on Quantitative Biology, sirtuin genes offer anti-aging benefits in a variety of species, including roundworms, fruit flies, and yeast (4). 

According to a 2012 animal study on male mice published in Nature, the overexpression of the SIRT6 gene may increase their lifespan by up to 15 percent (5). A 2006 study published in Cell has found corresponding results by discovering that deficiencies in SIRT6 may accelerate the aging process in mice (6). The anti-aging effects of SIRT6 may be the result of anti-cancer benefits.

A 2010 study published in the Archives of Biochemistry and Biophysics has found that SIRT1 may help to activate DNA repair proteins and support cellular repair (7). According to a 2008 study published in Cancer Cell, SIRT1 can support DNA damage recovery by helping to repair the double helix of the DNA (8).

According to a 2008 study published in the Proceedings of the National Academy of Sciences, SIRT1 also plays an important role in cellular autophagy by deacetylating autophagy genes (9). SIRT1 also supports mitochondrial autophagy, the detoxification of old cells, and cellular renewal. The effectiveness of sirtuins, however, may depend on cellular and mitochondrial health.

Benefits of Sirtuins 

According to a 2012 study published in the National Review of Molecular and Cellular Biology, sirtuins help to regulate fat and glucose metabolism, cellular and energy homeostasis, and increased lifespan (10). However, there are different types of sirtuins with different benefits. Let’s break it down.

SIRT1

SIRT1 offers the most science-backed benefits for your health. A 2017 study published in the International Journal of Molecular Medicine has found that SIRT1 is required for and supports mitochondrial biogenesis (11). According to a 2013 study published in PLoS One, it helps to regulate energy metabolism and supports the activation of thyroid T3 hormone (12).

According to a 2011 study published in Current Pharmaceutical Design, with the help of fasting, it may offer protection against neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease (13). 

A 2007 study published in Nature has found that it may help the treatment of insulin resistance and diabetes (14). According to a 2017 study published in Frontiers in Endocrinology, SIRT1 may help to reduce the risk of age-associated weight-gain by supporting leptin sensitivity (15).

According to a 2011 study published in Hepatology, it may help to support liver function and body homeostasis (16). Lastly, a 2010 study published in Biochemical and Biophysical Research Communications, SIRT may help human embryonic stem cell differentiation (17).

SIRT2

A 2012 study has found that SIRT2 may help to lower mitochondrial activity and fatty acid metabolism (18). It may help to support metabolism and reduce the risk of obesity.

SIRT3

A 2011 review published in Molecular Cell, SIRT3 may help to fight and reduce the risk of oxidative stress (19). According to a 2011 study published in Biochemical Journal, low levels of SIRT3 may be linked to insulin resistance and fatty liver disease (20).

SIRT4

A 2013 study published in Cancer Cell has found that SIRT may offer tumor-suppressive benefit (21). It may discourage mitochondrial glutamine metabolism and as a result, help to modulate metabolic response to DNA damage. According to a 2006 study published in Cell, SIRT4 may also help to reduce insulin secretion (22).

SIRT5

According to a 2006 study published in Cell, SIRT5 may help mitochondrial metabolism and ammonia detoxification and removal (22). A 2010 review published in Trends in Biochemical Sciences has found that SIRT6 helps to support genome stability and DNA repair. Low levels of SIRT6 may result in metabolic problems and age-related health issues (23).

SIRT6

A 2010 review published in Trends in Biochemical Sciences has found that SIRT6 helps to support genome stability and DNA repair. Low levels of SIRT6 may result in metabolic problems and age-related health issues (23).

SIRT7

A 2006 study published in Cell, has found that SIRT7 is important for both rDNA transcription and DNA repair mechanisms (22)

Downsides of Sirtuins

High levels of sirtuins are not always good. There are some downsides to sirtuins.  The key message here is that we need balanced activation that is optimized for the environmental conditions we are living in.  

SIRT1

According to a 2015 study published in The Journal of Experimental Medicine, SIRT1 may increase inflammation in multiple sclerosis and autoimmune issues (24). According to a 2011 study published in the Annals of Rheumatic Diseases, SIRT1 may lead to increased cytokine production in rheumatoid arthritis (25).

While a 2008 study published in Cell has found that SIRT1 may suppress tumors and helps DNA repair, a 2009 study published in Cancer Research has found that overexpression of SIRT1 may cause cancer (26, 27). Whether SIRT1 contributes to or stops cancer may lie in both autophagy and the survival effects of sirtuins.

SIRT2

A 2011 study published in the Proceedings of the National Academy of Sciences of the United States of America has found that SIRT2 is necessary for the myelination and regeneration of nerve cells (28). On the other hand, according to a 2011 study published in Human Molecular Genetics, excess SIRT2 may accumulate in neurons of the aging central nervous system (CNS) that may contribute to age-related brain issues (29).

How to Activate Healthy Expression of Sirtuins

While overexpression of sirtuins can have some drawbacks, overall, it seems that increasing sirtuins without overexpression can support your health and longevity in most cases. Here is how to activate the healthy expression of sirtuins.

Real Food Keto Diet

A ketogenic diet is a diet that’s very low in carbohydrates (5 to 10 percent), high in fats (65 to 75 percent), and offers moderate amounts of proteins (15 to 30 percent). A 2015 study published in Biogerontology has found that restricting glucose leads to increased NAD+ and sirtuin activity and as a result, may help to extend the lifespan of human fibroblast cells (30). Eating a ketogenic or keto diet is one of the best ways to restrict glucose. According to a 2013 research published in Frontiers in Aging Neuroscience, ketosis and ketones support sirtuin activity (31). 

On the other hand, a 2012 animal study published in IUBMB Life has found that a ketogenic diet supports mitochondrial function and increases brown fat production, however, reduces SIRT3 levels (32). It seems that overall, because of its low glucose levels, the ketogenic diet supports sirtuin production and function and also supports metabolic function.

When following a ketogenic diet, it is important that you follow a real food keto diet. While keeping to strict macronutrient ratios and a very low-carb diet, dirty keto is low in nutrients. It is important that you go beyond following the macronutrient principles of keto eat a nutrient-dense diet with whole foods. You can learn more about the difference between dirty keto and real food keto in this article. Here are some foods you should include in a real food keto diet.

Polyphenol Rich Foods 

According to a 2013 study published in the Journal of Nutrition, eating a diet high in polyphenols is linked to longevity and may decrease mortality in older adults (33). Researchers found a 30 percent reduced overall mortality in people who ate a diet rich in polyphenols (650 mg/day or more).

Foods that are high in polyphenols include bitter vegetables, olive oil, berries, coffee, green tea, dark chocolate, ginger, and turmeric.  Consuming these foods and herbs can help your body have balanced and optimized sirtuin activation.  

Zinc Rich Foods

Zinc is a very important nutrient that helps to keep your immune system strong. According to a 2016 study published in PLoS One, zinc may also increase both mean and maximum lifespan by supporting various longevity pathways (34).

Keto-friendly foods that are rich in zinc include shellfish, red meat, grass-fed dairy, eggs, nuts, seeds, spinach and kale,  You can learn more about the benefits and importance of zinc here.

Omega-3 Rich Foods

Omega-3 fatty acids are very important healthy fats that help reduce chronic inflammation. According to a 2013 study published in Aging (Albany, NY), omega-3 fish oil supplements help to lower inflammation and oxidative stress and as a result, may increase lifespan and decrease age-related diseases (35).

Foods that are rich in omega-3 fatty acids include wild-caught fish and seafood, algae, flax seeds, chia seeds, hemp seeds, walnuts, and flaxseed oil. You can learn more about omega-3 and omega-3 foods from this article.

Niacin Rich Foods 

Niacin or vitamin B3 is very important for brain and mental health among other functions. A 2013 study published in Nature Chemical Biology has found that niacin supports energy metabolism and lifespan (36).  Niacin is what forms NAD and nicotinamide adenine dinucleotide phosphate (NADP) and nicotinamide mononucleotide (NMN).  

Foods that are high in niacin include liver, other organ meats, grass-fed red meat, pasture-raised poultry, wild-caught fish, nutritional yeast, grass-fed dairy, algae, seaweed, and mushrooms. You can learn more about niacin by reading this article here.

Vitamin D Rich Foods

Vitamin D is one of the most important vitamins that’s essential for immune, bone, muscle, dental, brain, and mental health. According to a 2016 article published in Cell Reproduction, vitamin D supports a healthy stress response, protein homeostasis, and longevity (37).

Foods that are rich in vitamin D include oily fish, liver, organ meats, red meat, and egg yolks. You can learn more about vitamin D by reading this article.

Intermittent Fasting 

A 2012 study published in the Journal of Cell Biology has found the caloric restriction and fasting may help to improve SIRT2 and deacetylate various mitochondrial proteins (38). It is important to note that we are talking about calorie reduction without resulting in malnutrition. Practicing fasting or calorie restriction while still meeting nutritional needs and not getting malnourished is an effective way to reduce inflammation, prevent disease, and increase lifespan. 

According to a 2009 animal study on rhesus monkeys published in Science, caloric reduction without malnutrition can lower mortality (39). A 2015 review published in Aging Research Reviews has found that caloric restriction may improve stress response, reduce age-related disease, support metabolism, and reduce the aging process (40).

According to a 2005 study, the longevity benefits of caloric restriction and fasting requires SIRT1 to draw the connection between fasting, sirtuins, and longevity (41).  Sirtuins are a part of the cellular signaling for the process of autophagy in which the cells clear out damaged proteins.

How to Practice Intermittent Fasting

Intermittent fasting is just one form of fasting you can practice. This form of fasting cycles between a period of fasting (not eating) and feasting (eating) within a day. If you are new to intermittent fasting, I recommend that you start with the Simple Fast. This beginner-friendly intermittent fasting method involves 12 hours of fasting including your overnight sleep.

After your 6 pm dinner, stop eating. You will be ready to eat your breakfast, 12 hours later at 6 am. Gradually increase your fasting window. You will likely find it easy to push breakfast to 7 or 8 am, and eventually to 9 or 10 am. Most people find the 16:8 method (16 hours of fasting and an 8-hour window for eating) the most beneficial, however, listen to your body. To learn more about intermittent fasting, I recommend reading this article.

Extended Fasting and Partial Fasting

Intermittent fasting is not the only way to experience the benefits of fasting on sirtuins (38, 39, 40, 41). If you are experienced with intermittent fasting, I recommend trying an extended fast. An extended fast means that you are fasting for an extended period of type. It may only be for a day if you are new, or 2 to 3 days, 5 to 7 days. During this time, all you are consuming is non-caloric beverages, such as purified water and herbal tea. You may learn more about extended fasting in this article.

If you are not quite ready to give food up completely but want to give a break to your digestion and support cellular repair, I recommend partial fasting. There are a variety of partial fasts out there. The Bone Broth Fast and Green Juice Fasting involve drinking high-nutrient liquids – bone broth or green juices respectively – to nourish your cells while taking a break from food.

The Fasting Mimicking Diet® or FMD® focuses on caloric restriction for a period of time following a very specific plan. Keto or Fat Fasting combines the benefits of the ketogenic diet and partial fasting.

The Daniel Fast is a 10 to 21 day fast following a nutrient-dense, plant-based diet based on Biblical principles. No matter which partial fasting method speaks to you, you can experience the sirtuin-supporting benefits of fasting and caloric restriction. To learn more about these partial fasting strategies, I recommend reading this article.

Feast/Famine Cycling

When we talk about fasting, we tend to focus on the ‘not eating’ part and forget about our nutrition. As you’ve learned, research has found that while fasting can benefit sirtuins, it is important that you don’t become malnourished (38, 39, 40, 41).

It is important that you nourish your body with nutrient-dense foods, including greens, vegetables, herbs, spices, low-glycemic index fruits, healthy fats, grass-fed beef, pasture-raised poultry and eggs, and wild-caught fish during your feasting window. To learn more about feast/famine cycling, I recommend reading this article.

Regular Movement and Exercise

Movement and exercise are incredibly important for your health, including for improving sirtuins and longevity. According to a 2009 study published in Mechanisms in Aging and Development, exercise offers anti-inflammatory and antioxidative benefits and can increase SIRT1.

SIRT1 can support the long-term benefits of exercise (42). According to a 2011 study published in Molecular Cell, cycling-AMP (cAMP) pathways, which are activated during high-energy demands, such as high-intensity exercise or cold-exposure, can activate SIRT1 (43). 

I highly recommend any high-intensity interval training (HIIT) workouts, however, other forms of exercise can benefit your sirtuins and longevity as well. I recommend that you mix up cardiovascular, such as trampoline workouts, jogging, dancing, biking, or swimming, strength- and resistance training, such as bodyweight workouts, weightlifting, kettlebell workouts, and TRX, and low-impact workouts, such as yoga, Pilates, Tai Chi, and Barre workouts. Additionally, stay active throughout the day through walking, stretching regularly, taking a bike ride, dancing, and playing with your kids or pets.

Reduce Stress and Optimize Sleep

According to a 2013 study published in Science, sirtuins are important circadian rhythms (44). When your circadian rhythms are not balanced, SIRT1 and SIRT3 activity will drop and you will experience lower energy levels. 

To reduce your stress levels I recommend that you practice meditation, breathwork, guided muscle relaxation, guided visualization, gratitude, grounding, time in nature, and mindset shifts. Consciously shift your energy from negative energy and stress as much as possible. For example, instead of refreshing the news every second, you may want to catch the highlights once a day.

Learn to shift your mindset and find the positive in everything and trust the process. Prayer can provide real guidance. Spend time with uplifting and supportive friends and family and seek a supportive community.

To support your sleep, develop a nighttime routine that relaxes you. Avoid electronics, the news, stress, food, and caffeine. Try stretching, meditation, prayer, reading, coloring, or positive conversations. Take a healing bath or sip on herbal tea. Make sure to go to bed and wake up at the same time every day to support your circadian rhythms.

Heat Exposure and Infrared Sauna Therapy

According to a 2013 dissertation at the University of Florida, heat exposure and sweating from saunas can increase NAD+ and consequently SIRT1 levels (45). This benefit from sweating may contribute to some of the benefits you experience during exercise as well. Infrared sauna is more effective than regular saunas.

While a regular sauna uses only heat from wood-burning, electricity, or steam for sweating and detoxification, an infrared sauna is a sauna that releases infrared light. Infrared light is safe and goes deeper into your body allowing you to release fat-soluble toxins, lower toxic burdens, and even enhance internal detox pathways as well. To learn more about infrared sauna, I recommend reading this article. 

Cold Exposure and Cold Showers

Just like heat exposure, cold exposure can also help to activate sirtuins for healthy aging. A 2011 study published in Molecular Cell has found that cycling-AMP (cAMP) pathways, which are activated during high-energy demands can activate SIRT1 (43). This high-energy demand can come from cold exposure. Cold showers are a simple yet effective strategy for cold-exposure.

If you are not yet ready for a completely cold shower, you may want to finish your shower with cold water. Alternating between cold and hot can be effective as well. You can alternate between cold and hot water during your shower, finish your shower with cold water, jump into a cold pool after sitting in the sauna, or taking a cold shower after using your infrared sauna are all great ideas.

Top Supplements       

Certain supplements can also help to activate and support sirtuins and increase longevity.  The lifestyle strategies mentioned above are the most important factors in activating sirtuin activity but these supplements can also be helpful.  

Resveratrol & Quercetin 

Resveratrol is a polyphenol found in the skin of grapes, berries, and red wine. Quercetin is a flavonoid found in various plant foods, including onions, green tea, apples, berries, Ginkgo biloba. They both offer anti-inflammatory and oxidation-reducing benefits. According to a 2010 study, resveratrol helps to mimic calorie restriction, support sirtuins, reduce inflammation, and increase longevity (46).

According to a 2020 study published in Frontiers in Pharmacology, quercetin is a natural phytochemical that can help to activate SIRT1 (47). 

Magnesium 

Magnesium is a mineral that’s important for muscle health, nerve function, brain health, mental health, relaxation, healthy blood pressure, and immune health. According to a 2017 study published in Health, magnesium can activate the anti-aging benefits of sirtuins and may help to reverse Alzheimer’s disease and diabetes (48).

Melatonin 

Melatonin is a hormone primarily released by the pineal gland that supports your circadian rhythm and sleep-wake cycle. Melatonin supplements support sleep and reduce insomnia.

According to a 2020 study published in Frontiers in Physiology, SIRT1 can help to regulate cardiac function, and melatonin can support SIRT1 activity, lower inflammation, reduce oxidative stress, and reduce the risk of obesity-related heart injury (49). 

Final Thoughts on Sirtuins

Sirtuins are a group of proteins that regulate cellular health and homeostasis, support energy metabolism, improve brain health, help cellular repair, and support longevity.

We are certainly at the beginning of understanding the phenomenon of these proteins. Every year new pieces of information are obtained, but there is still a long way to create the perfect anti-aging panacea. Biological aging is a complex process affected by many factors, such as environment, species, and individual characteristics of the population. Therefore, scientists will undoubtedly invest a lot of invention, creativity, and effort before solving the mystery of aging and manipulating this process by selected factors.

 

Sources in This Article Include:

1. https://jlb.onlinelibrary.wiley.com/doi/full/10.1189/jlb.1112557

2. https://www.jneurosci.org/content/30/30/10220 

3. Kaeberlein M, McVey M, Guarente L. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev. 1999 Oct 1;13(19):2570-80. doi: 10.1101/gad.13.19.2570. PMID: 10521401

4. Guarente L. Sirtuins in aging and disease. Cold Spring Harb Symp Quant Biol. 2007;72:483-8. doi: 10.1101/sqb.2007.72.024. PMID: 18419308

5. Kanfi, Y., Naiman, S., Amir, G. et al. The sirtuin SIRT6 regulates lifespan in male mice. Nature 483, 218–221 (2012). Link Here

6. Mostoslavsky R, Chua KF, Lombard DB, Pang WW, Fischer MR, Gellon L, Liu P, Mostoslavsky G, Franco S, Murphy MM, Mills KD, Patel P, Hsu JT, Hong AL, Ford E, Cheng HL, Kennedy C, Nunez N, Bronson R, Frendewey D, Auerbach W, Valenzuela D, Karow M, Hottiger MO, Hursting S, Barrett JC, Guarente L, Mulligan R, Demple B, Yancopoulos GD, Alt FW. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell. 2006 Jan 27;124(2):315-29. doi: 10.1016/j.cell.2005.11.044. PMID: 16439206

7. Chung S, Yao H, Caito S, Hwang JW, Arunachalam G, Rahman I. Regulation of SIRT1 in cellular functions: role of polyphenols. Arch Biochem Biophys. 2010 Sep 1;501(1):79-90. doi: 10.1016/j.abb.2010.05.003. Epub 2010 May 5. PMID: 20450879

8. Wang RH, Sengupta K, Li C, Kim HS, Cao L, Xiao C, Kim S, Xu X, Zheng Y, Chilton B, Jia R, Zheng ZM, Appella E, Wang XW, Ried T, Deng CX. Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice. Cancer Cell. 2008 Oct 7;14(4):312-23. doi: 10.1016/j.ccr.2008.09.001. PMID: 18835033

9.I n Hye Lee, Liu Cao, Raul Mostoslavsky, David B. Lombard, Jie Liu, Nicholas E. Bruns, Maria Tsokos, Frederick W. Alt, Toren Finkel. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proceedings of the National Academy of Sciences Mar 2008, 105 (9) 3374-3379. Link Here

10. Houtkooper RH, Pirinen E, Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol. 2012 Mar 7;13(4):225-238. doi: 10.1038/nrm3293. PMID: 22395773

11. Li P, Liu Y, Burns N, Zhao KS, Song R. SIRT1 is required for mitochondrial biogenesis reprogramming in hypoxic human pulmonary arteriolar smooth muscle cells. Int J Mol Med. 2017 May;39(5):1127-1136. doi: 10.3892/ijmm.2017.2932. Epub 2017 Mar 22. PMID: 28339017

12. Suh JH, Sieglaff DH, Zhang A, Xia X, Cvoro A, Winnier GE, Webb P. SIRT1 is a direct coactivator of thyroid hormone receptor β1 with gene-specific actions. PLoS One. 2013 Jul 26;8(7):e70097. doi: 10.1371/journal.pone.0070097. PMID: 23922917

13. Srivastava S, Haigis MC. Role of sirtuins and calorie restriction in neuroprotection: implications in Alzheimer’s and Parkinson’s diseases. Curr Pharm Des. 2011;17(31):3418-33. doi: 10.2174/138161211798072526. PMID: 21902666

14. Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, Jin L, Boss O, Perni RB, Vu CB, Bemis JE, Xie R, Disch JS, Ng PY, Nunes JJ, Lynch AV, Yang H, Galonek H, Israelian K, Choy W, Iffland A, Lavu S, Medvedik O, Sinclair DA, Olefsky JM, Jirousek MR, Elliott PJ, Westphal CH. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007 Nov 29;450(7170):712-6. doi: 10.1038/nature06261. PMID: 18046409

15. Tsotomu S. Age-Associated Weight Gain, Leptin, and SIRT1: A Possible Role for Hypothalamic SIRT1 in the Prevention of Weight Gain and Aging through Modulation of Leptin Sensitivity  . Frontiers in Endocrinology. 2017. Link Here

16. Jin J, Iakova P, Jiang Y, Medrano EE, Timchenko NA. The reduction of SIRT1 in livers of old mice leads to impaired body homeostasis and to inhibition of liver proliferation. Hepatology. 2011 Sep 2;54(3):989-98. doi: 10.1002/hep.24471. Epub 2011 Jul 27. PMID: 21638299

17. hang Y, Wang J, Chen G, Fan D, Deng M. Inhibition of Sirt1 promotes neural progenitors toward motoneuron differentiation from human embryonic stem cells. Biochem Biophys Res Commun. 2011 Jan 14;404(2):610-4. doi: 10.1016/j.bbrc.2010.12.014. Epub 2010 Dec 7. PMID: 21144831

18. Krishnan J, Danzer C, Simka T, Ukropec J, Walter KM, Kumpf S, Mirtschink P, Ukropcova B, Gasperikova D, Pedrazzini T, Krek W. Dietary obesity-associated Hif1α activation in adipocytes restricts fatty acid oxidation and energy expenditure via suppression of the Sirt2-NAD+ system. Genes Dev. 2012 Feb 1;26(3):259-70. doi: 10.1101/gad.180406.111. PMID: 22302938

19. Bell EL, Guarente L. The SirT3 divining rod points to oxidative stress. Mol Cell. 2011 Jun 10;42(5):561-8. doi: 10.1016/j.molcel.2011.05.008. PMID: 21658599

20. Agnieszka A. Kendrick, Mahua Choudhury, Shaikh M. Rahman, Carrie E. McCurdy, Marisa Friederich, Johan L. K. Van Hove, Peter A. Watson, Nicholas Birdsey, Jianjun Bao, David Gius, Michael N. Sack, Enxuan Jing, C. Ronald Kahn, Jacob E. Friedman, Karen R. Jonscher; Fatty liver is associated with reduced SIRT3 activity and mitochondrial protein hyperacetylation. Biochem J 1 February 2011; 433 (3): 505–514. Link Here

21. Jeong SM, Xiao C, Finley LW, Lahusen T, Souza AL, Pierce K, Li YH, Wang X, Laurent G, German NJ, Xu X, Li C, Wang RH, Lee J, Csibi A, Cerione R, Blenis J, Clish CB, Kimmelman A, Deng CX, Haigis MC. SIRT4 has tumor-suppressive activity and regulates the cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism. Cancer Cell. 2013 Apr 15;23(4):450-63. doi: 10.1016/j.ccr.2013.02.024. Epub 2013 Apr 4. PMID: 23562301

22. Haigis MC. SIRT4 Inhibits Glutamate Dehydrogenase and Opposes the Effects of Calorie Restriction in Pancreatic β Cells. Cell. 2006. Link Here

23. Tennen RI, Chua KF. Chromatin regulation and genome maintenance by mammalian SIRT6. Trends Biochem Sci. 2011 Jan;36(1):39-46. doi: 10.1016/j.tibs.2010.07.009. Epub 2010 Aug 21. PMID: 20729089

24. Lim HW, Kang SG, Ryu JK, Schilling B, Fei M, Lee IS, Kehasse A, Shirakawa K, Yokoyama M, Schnölzer M, Kasler HG, Kwon HS, Gibson BW, Sato H, Akassoglou K, Xiao C, Littman DR, Ott M, Verdin E. SIRT1 deacetylates RORγt and enhances Th17 cell generation. J Exp Med. 2015 May 4;212(5):607-17. doi: 10.1084/jem.20132378. Epub 2015 Apr 27. Erratum in: J Exp Med. 2015 Jun 1;212(6):973. PMID: 25918343

25. Niederer F, Ospelt C, Brentano F, Hottiger MO, Gay RE, Gay S, Detmar M, Kyburz D. SIRT1 overexpression in the rheumatoid arthritis synovium contributes to proinflammatory cytokine production and apoptosis resistance. Ann Rheum Dis. 2011 Oct;70(10):1866-73. doi: 10.1136/ard.2010.148957. Epub 2011 Jul 8. PMID: 21742641

26.Oberdoerffer P, Michan S, McVay M, Mostoslavsky R, Vann J, Park SK, Hartlerode A, Stegmuller J, Hafner A, Loerch P, Wright SM, Mills KD, Bonni A, Yankner BA, Scully R, Prolla TA, Alt FW, Sinclair DA. SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell. 2008 Nov 28;135(5):907-18. doi: 10.1016/j.cell.2008.10.025. PMID: 19041753

27. Liu T, Liu PY, Marshall GM. The critical role of the class III histone deacetylase SIRT1 in cancer. Cancer Res. 2009 Mar 1;69(5):1702-5. doi: 10.1158/0008-5472.CAN-08-3365. Epub 2009 Feb 24. PMID: 19244112 

28. Beirowski B, Gustin J, Armour SM, Yamamoto H, Viader A, North BJ, Michán S, Baloh RH, Golden JP, Schmidt RE, Sinclair DA, Auwerx J, Milbrandt J. Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling. Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):E952-61. doi: 10.1073/pnas.1104969108. Epub 2011 Sep 26. PMID: 21949390

29. Maxwell MM, Tomkinson EM, Nobles J, Wizeman JW, Amore AM, Quinti L, Chopra V, Hersch SM, Kazantsev AG. The Sirtuin 2 microtubule deacetylase is an abundant neuronal protein that accumulates in the aging CNS. Hum Mol Genet. 2011 Oct 15;20(20):3986-96. doi: 10.1093/hmg/ddr326. Epub 2011 Jul 26. PMID: 21791548

30. Yang NC, Song TY, Chang YZ, Chen MY, Hu ML. Up-regulation of nicotinamide phosphoribosyltransferase and increase of NAD+ levels by glucose restriction extend replicative lifespan of human fibroblast Hs68 cells. Biogerontology. 2015 Feb;16(1):31-42. doi: 10.1007/s10522-014-9528-x. Epub 2014 Aug 22. PMID: 25146190

31. Duan W. Frontiers in Aging Neuroscience . 2013. Link Here

32. Srivastava S, Baxa U, Niu G, Chen X, Veech RL. A ketogenic diet increases brown adipose tissue mitochondrial proteins and UCP1 levels in mice. IUBMB Life. 2013 Jan;65(1):58-66. doi: 10.1002/iub.1102. Epub 2012 Dec 10. Erratum in: IUBMB Life. 2014 Jul;66(7):519. PMID: 23233333

33. R. Zamora-Ros, M. Rabassa, A. Cherubini, M. Urpi-Sarda, S. Bandinelli, L. Ferrucci, C. Andres-Lacueva. High Concentrations of a Urinary Biomarker of Polyphenol Intake Are Associated with Decreased Mortality in Older Adults. Journal of Nutrition, 2013; 143 (9). Link Here

34. Kumar J, Barhydt T, Awasthi A, Lithgow GJ, Killilea DW, Kapahi P. Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans. PLoS One. 2016 Apr 14;11(4):e0153513. doi: 10.1371/journal.pone.0153513. PMID: 27078872

35. de Magalhães JP, Müller M, Rainger GE, Steegenga W. Fish oil supplements, longevity and aging. Aging (Albany NY). 2016 Aug;8(8):1578-82. doi: 10.18632/aging.101021. PMID: 27564420

36. Sandra Weimer, Steffen Priebe, Ines Heiland, Marc Birringer, Marco Groth, Alexandra Segref, Yariv Kanfi, Nathan L Price, Sebastian Schmeisser, Stefan Schuster, Andreas F H Pfeiffer, Reinhard Guthke, Matthias Platzer, Thorsten Hoppe, Haim Y Cohen, Kim Zarse, David A Sinclair, Michael Ristow. Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide. Nature Chemical Biology, 2013; Link Here

37. Mark KA, Dumas KJ, Bhaumik D, Schilling B, Davis S, Oron TR, Sorensen DJ, Lucanic M, Brem RB, Melov S, Ramanathan A, Gibson BW, Lithgow GJ. Vitamin D Promotes Protein Homeostasis and Longevity via the Stress Response Pathway Genes skn-1, ire-1, and xbp-1. Cell Rep. 2016 Oct 25;17(5):1227-1237. doi: 10.1016/j.celrep.2016.09.086. PMID: 27783938

38. Riekelt H. Houtkooper, Johan Auwerx; Exploring the therapeutic space around NAD+. J Cell Biol 15 October 2012; 199 (2): 205–209. Link Here

39. Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, Allison DB, Cruzen C, Simmons HA, Kemnitz JW, Weindruch R. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science. 2009 Jul 10;325(5937):201-4. doi: 10.1126/science.1173635. PMID: 19590001

40. Donald K. Ingram, George S. Roth, Calorie restriction mimetics: Can you have your cake and eat it, too?, Ageing Research Reviews. 2015. Link Here

41. Chen D, Steele AD, Lindquist S, Guarente L. Increase in activity during calorie restriction requires Sirt1. Science. 2005 Dec 9;310(5754):1641. doi: 10.1126/science.1118357. PMID: 16339438

42. Csiszar A, Labinskyy N, Jimenez R, Pinto JT, Ballabh P, Losonczy G, Pearson KJ, de Cabo R, Ungvari Z. Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging: role of circulating factors and SIRT1. Mech Ageing Dev. 2009 Aug;130(8):518-27. doi: 10.1016/j.mad.2009.06.004. Epub 2009 Jun 21. PMID: 19549533

43. Zachary Gerhart-Hines, John E. Dominy, Sharon M. Blättler, Mark P. Jedrychowski, Alexander S. Banks, Ji-Hong Lim, Helen Chim, Steven P. Gygi, Pere Puigserver,

The cAMP/PKA Pathway Rapidly Activates SIRT1 to Promote Fatty Acid Oxidation Independently of Changes in NAD+, Molecular Cell. Link Here

44. The coenzyme nicotinamide adenine dinucleotide mechanistically links the circadian clock to control of energy production by mitochondria. Science. 2013. Link Here

45. Raynes RR. SIRT1 Regulation of the Heat Shock Response in an HSF1-Dependent Manner and the Impact of Caloric Restriction. 2013. Link Here

46. Baur JA. Resveratrol, sirtuins, and the promise of a DR mimetic. Mech Ageing Dev. 2010 Apr;131(4):261-9. doi: 10.1016/j.mad.2010.02.007. Epub 2010 Feb 26. PMID: 20219519

47. Concetta E. SIRT1 Activation by Natural Phytochemicals: An Overview. Frontiers in Pharmacology. 2020. Link Here 

48. Martins, I. J. (2016). Magnesium therapy prevents senescence with the reversal of diabetes and Alzheimer’s disease. Health, 8(7), 694-710. Link Here

49. Gaia F. Sirtuin1 Role in the Melatonin Protective Effects Against Obesity-Related Heart Injury. Frontiers in Physiology. 2020. Link Here

50. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821238/ (Jan 2023)

Main Source and Reference: https://drjockers.com/sirtuins/