Magazine | The role of insulin and insulin resistance in longevity

The role of insulin and insulin resistance in longevity

Written by Ali Boukllouâ 7 min read
 The role of insulin and insulin resistance in longevity

Longevity is the ultimate goal for those seeking a longer, healthier, and more fulfilling life. While factors like diet, exercise, and stress management are crucial, the regulation of insulin levels and insulin resistance also play a significant role. But why is this so important, and how can we influence it? This article delves into the scientific foundations of insulin and insulin resistance, explores their impacts on health, and offers practical tips for reducing insulin resistance. 

What are insulin and insulin resistance? 

Insulin is a hormone produced in the pancreas that is essential for regulating blood sugar levels. It helps cells in muscles, fat, and the liver absorb glucose from the blood to use as energy or store as glycogen. Insulin plays a crucial role in carbohydrate, fat, and protein metabolism. 

Insulin resistance occurs when cells in muscles, fat, and the liver do not respond well to insulin, leading to elevated blood sugar levels. This prompts the pancreas to produce more insulin to compensate. Over time, this can result in hyperinsulinemia (excessively high insulin levels) and eventually type 2 diabetes mellitus, heart disease, and other metabolic disorders. 

Scientific foundations and mechanisms 

1. Insulin and glucose homeostasis 

Mechanism: Insulin regulates blood sugar levels by promoting the transport of glucose into cells. In insulin resistance, however, cells respond poorly to insulin, causing glucose to remain in the blood. This leads to chronically elevated blood sugar levels, which can promote inflammation and oxidative stress. 

Study: According to DeFronzo et al. (2009), insulin resistance is not just a precursor to type 2 diabetes mellitus, but also a central factor in the development of cardiometabolic diseases like hypertension and atherosclerosis. 

2. Insulin and fat storage 

Mechanism: Insulin promotes fat storage by inhibiting fat breakdown (lipolysis) and stimulating fat synthesis (lipogenesis). Elevated insulin levels, which are common in insulin resistance, can thus lead to increased fat storage, particularly in the abdominal area. 

Study: A study by Weiss et al. (2016) showed that insulin resistance and hyperinsulinemia are both causes and consequences of obesity, which in turn increases the risk for cardiovascular diseases. 

3. Insulin and cellular aging 

Mechanism: Chronically high insulin levels and insulin resistance can accelerate cellular aging by reducing the activity of telomerase (the enzyme that protects telomeres) and increasing oxidative stress. This can lead to accelerated aging of cells. 

Study: Research by Qin et al. (2016) indicates that insulin resistance and elevated insulin levels promote cellular aging through increased cell damage and age-related degeneration. 

Insulin resistance and chronic diseases 

Insulin resistance is directly related to a variety of chronic diseases that can significantly impair quality of life and lifespan. Here are some of these diseases and their connection to insulin resistance: 

1. Cardiovascular diseases 

Elevated insulin levels and insulin resistance are strong predictors of cardiovascular diseases. Insulin resistance leads to increased production of free radicals, which can damage arterial walls and promote inflammatory processes. 

Study: According to an analysis by Reaven (1988), insulin resistance is the primary cause of metabolic syndrome, a cluster of risk factors for heart disease and stroke.  

2. Type 2 diabetes mellitus 

Persistent high blood sugar levels due to insulin resistance can exhaust the insulin-producing beta cells in the pancreas, ultimately leading to type 2 diabetes mellitus. 

Study: Unger and Orci (2001) explain that insulin resistance plays a key role in the pathophysiology of type 2 diabetes mellitus and can cause long-term complications such as kidney failure and neuropathy. 

3. Obesity 

Elevated insulin levels favor fat storage, leading to obesity and further metabolic disturbances. 

Study: Eckel et al. (2005) demonstrate that insulin resistance is both a cause and a consequence of obesity, creating a vicious cycle that is hard to break.  

4. Neurodegenerative diseases 

Recent research suggests that insulin resistance can also increase the risk for neurodegenerative diseases like Alzheimer’s. 

Study: A study by Craft et al. (2012) shows that insulin resistance and hyperinsulinemia significantly increase the risk for cognitive impairment and Alzheimer’s disease. 

Practical tips for reducing insulin resistance

The good news is that insulin resistance can be reduced through specific lifestyle changes and dietary strategies. Here are some scientifically supported approaches: 

1. Diet 

Low-carb or ketogenic diet: A low-carb diet can help lower insulin levels and improve insulin sensitivity. These diets focus on reducing sugar and starchy foods while emphasizing healthy fats and proteins. 

Study: Hu et al. (2015) found that low-carb diets are effective in controlling blood sugar levels and body weight. 

Fiber-rich foods: Fiber slows the absorption of sugar into the blood and improves insulin sensitivity. Foods such as vegetables, fruits, whole grains, and legumes are high in fiber. 

Study: Weickert and Pfeiffer (2008) demonstrated that fiber improves metabolic health and reduces the risk of insulin resistance. Specific recommendations include carrots, berries, spinach, and oatmeal. 

2. Exercise 

Strength training: Regular strength training helps build muscle mass and increases muscle insulin sensitivity. This leads to better glucose uptake and lower overall blood sugar levels. 

Study: Holten et al. (2004) showed that strength training significantly improves insulin sensitivity in patients with type 2 diabetes mellitus. 

Aerobic exercise: Aerobic activities such as running, cycling, or swimming improve insulin sensitivity and help regulate blood sugar levels. 

Study: Ross et al. (2000) found that regular aerobic exercise improves insulin sensitivity in overweight and obese adults. A 30-minute walk after meals could be a practical recommendation. 

3. Weight Management 

Weight reduction: Even moderate weight loss can significantly improve insulin sensitivity and reduce the risk of type 2 diabetes mellitus. 

Study: Knowler et al. (2002) showed that a weight reduction of just 7% of body weight lowered the risk of developing type 2 diabetes mellitus by 58%. Regular monitoring of BMI and waist circumference can be helpful.  

4. Sleep 

Improved sleep hygiene: Adequate and high-quality sleep supports metabolic health and can help reduce insulin resistance. 

Study: Buxton and Marcelli (2010) found that sleep deprivation significantly impairs insulin sensitivity. Specific tips include securing 7-8 hours of sleep and maintaining consistent sleep schedules. 

5. Stress management 

Stress reduction: Chronic stress can raise insulin levels and lead to insulin resistance. Techniques such as meditation, yoga, and mindfulness can help lower stress levels. 

Study: Black and Slavich (2016) demonstrated that mindfulness practices improve insulin sensitivity and reduce inflammation. 

Additional measures to improve insulin sensitivity 

1. Intermittent fasting 

Intermittent fasting (IF) can be an effective method to improve insulin sensitivity. Various methods include 16:8 (16 hours fasting, 8 hours eating) or 5:2 (5 days normal eating, 2 days calorie restriction). 

Study: Tinsley and La Bounty (2015) found that intermittent fasting can improve insulin sensitivity and lower insulin levels. 

2. Nutritional supplements 

Certain nutritional supplements have been proven to improve insulin sensitivity, including magnesium, omega-3 fatty acids, and berberine. 

  • Magnesium: A study by Guerrero-Romero and Rodriguez-Moran (2011) showed that magnesium improves insulin sensitivity and blood sugar levels. 
  • Omega-3 fatty acids: According to a meta-analysis by Balk et al. (2006), omega-3 fatty acids improve insulin sensitivity and reduce inflammation. 
  • Berberine: A study by Yin et al. (2008) showed that berberine improves insulin sensitivity in patients with type 2 diabetes mellitus. 

3. Hydration 

Adequate hydration is also crucial for maintaining healthy insulin sensitivity. 

Study: A study by Heiss et al. (2017) showed that dehydration can reduce insulin sensitivity. 

Conclusion 

Insulin and insulin resistance play a crucial role in health and longevity. Chronically high insulin levels and insulin resistance can lead to numerous health issues, accelerating aging and diminishing quality of life. Fortunately, there are many proven strategies for improving insulin sensitivity and reducing insulin resistance. A combination of a healthy diet, regular exercise, adequate sleep, and effective stress management can significantly enhance health and promote a long, fulfilling life. 

Published: January 2nd, 2025 · Updated: February 3rd, 2025

References

1. Balk, E. M., Lichtenstein, A. H., Chung, M., Kupelnick, B., Chew, P., & Lau, J. (2006). Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systematic review. Atherosclerosis, 189(1), 19-30.
2. Black, D. S., & Slavich, G. M. (2016). Mindfulness meditation and the immune system: a systematic review of randomized controlled trials. Annals of the New York Academy of Sciences, 1373(1), 13-24.
3. Buxton, O. M., & Marcelli, E. (2010). Short and long sleep are positively associated with obesity, diabetes, hypertension, and cardiovascular disease among adults in the United States. Social Science & Medicine, 71(5), 1027-1036.
4. Craft, S., & Watson, G. S. (2004). Insulin and neurodegenerative disease: shared and specific mechanisms. The Lancet Neurology, 3(3), 169-178.
5. DeFronzo, R. A., Ferrannini, E., Zimmet, P., & Alberti, G. (2009). International textbook of diabetes mellitus, two-volume set. John Wiley & Sons. - Eckel, R. H., Grundy, S. M., & Zimmet, P. Z. (2005). The metabolic syndrome. The Lancet, 365(9468), 1415-1428.
6. Guerrero-Romero, F., & Rodriguez-Moran, M. (2011). Magnesium improves the beta-cell function to compensate variation of insulin sensitivity: double-blind, randomized clinical trial. European journal of clinical investigation, 41(4), 405-410.
7. Heiss, C., Jahn, S., Taylor, M., Real, W. M., Angeli, F. S., Wong, M. L., ... & Glasser, S. P. (2017). Hypertension, dehydration, and glucose intolerance among southern California fire fighters. Occupational medicine, 67(1), 94-101.
8. Heiss, C., Jahn, S., Taylor, M., Real, W. M., Angeli, F. S., Wong, M. L., ... & Glasser, S. P. (2017). Hypertension, dehydration, and glucose intolerance among southern California fire fighters. Occupational medicine, 67(1), 94-101.
9. Holten, M. K., Zacho, M., Gaster, M., Juel, C., Wojtaszewski, J. F., & Dela, F. (2004). Strength training increases insulin-mediated glucose uptake, GLUT4 content, and insulin signaling in skeletal muscle in patients with type 2 diabetes mellitus. Diabetes, 53(2), 294-305.
10. Hu, T., Mills, K. T., Yao, L., Demanelis, K., Eloustaz, M., Yancy, W. S., & He, J. (2015). Effects of low-carbohydrate diets versus low-fat diets on metabolic risk factors: a meta-analysis of randomized controlled clinical trials. American Journal of Epidemiology, 182(5), 374-384.
11. Knowler, W. C., Barrett-Connor, E., Fowler, S. E., Hamman, R. F., Lachin, J. M., Walker, E. A., & Nathan, D. M. (2002). Reduction in the incidence of type 2 diabetes mellitus with lifestyle intervention or metformin. New England Journal of Medicine, 346(6), 393-403.
12. Qin, L., Li, J., & Wang, W. (2016). Mechanistic insights into the interaction between mitochondrial dysfunction and intact insulin signalling. Endocrine connections, 5(1), R35-R64.
13. Reaven, G. M. (1988). Banting lecture 1988. Role of insulin resistance in human disease. Diabetes, 37(12), 1595-1607.
14. Ross, R., Janssen, I., Dawson, J., Kungl, A. M., Kuk, J. L., Wong, S. L., ... & Hudson, R. (2000). Exercise-induced reduction in obesity and insulin resistance in women: a randomized controlled trial. Obesity research, 8(6), 452-460.
15. Tinsley, G. M., & La Bounty, P. M. (2015). Effects of intermittent fasting on body composition and clinical health markers in humans. Nutrition Reviews, 73(10), 661-674.
16. Unger, R. H., & Orci, L. (2001). Diseases of liporegulation: new perspective on obesity and related disorders. The FASEB Journal, 15(2), 312-321.
17. Weickert, M. O., & Pfeiffer, A. F. H. (2008). Metabolic effects of dietary fiber consumption and prevention of diabetes mellitus. The Journal of Nutrition, 138(3), 439-442.
18. Weiss, R., Bremer, A. A., & Lustig, R. H. (2016). What is metabolic syndrome, and why are children getting it? Annals of the New York Academy of Sciences, 1281(1), 123-140.
19. Yin, J., Xing, H., & Ye, J. (2008). Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism, 57(5), 712-717.

Author: Ali Boukllouâ

As a Doctor for Cardiology, Sports and Preventive Medicine, and as an entrepreneur, my mission is to improve health and well-being sustainably for longer, happier lives. At PreventicsOne, I use advanced diagnostics for early disease detection. As Team Doctor at ROWE Racing (GT3), I blend my passion for motorsport with medical expertise to enhance team performance and well-being. With Dogscan, I aim to revolutionize lung cancer detection through the incredible scent capabilities of dogs.

Discover trusted longevity brands
and expert health stacks

Stop wasting money on ineffective products
Save up to 5 hours of research per week
Delivered to your inbox every Thursday

You might also like

Founder interview: Dr. Emil Kendziorra, Founder & CEO at Tomorrow Biostasis
Lifespan Extension Interventions

3 min read

Founder interview: Dr. Emil Kendziorra, Founder & CEO at Tomorrow Biostasis

In our Founder Interview series, we highlight the brightest minds in preventive health, wellness, and longevity. In Episode 6, we’re honored to feature Dr. Emil Kenziorra, founder and CEO at Tomorrow Biostasis—one of the world-leading human cryopreservation experts.Tell us a little about yourself and your current ventureDoctor and researcher by training, entrepreneur by trade. Longevity has always been my motivation, with a focus on maximal life span extension. I'm running Tomorrow.bio and the non-profit European Biostasis Foundation to push human cryopreservation forward.How do you balance the demands of running a business while maintaining your own health and longevity?I've always worked a lot and my natural stress level is pretty low, plus good sleep and working out regularly. So all good :) Do you have a personal health goal? What is it? Not die - indefinitely, until I change my mind :)Before launching Tomorrow Biostasis, can you walk us through the “aha” moment that inspired the creation of your service?I've been involved in the longevity space in same capacity since 2007. I took a deep dive again in 2019 and after selling my last company in 2020, I switch to cryopreservation. There just isn't any meaningful progress in the field, with the billions of spending and decades of research maximum life span has not been extended by even a day. What sets Tomorrow Bio apart in the health and wellness industry?Accepting that maximal life span extension is not likely if we look at progress so far. If someone wants to live longer than currently possible, cryopreservation will be a necessary stopgap measure.What is the most groundbreaking or unexpected finding in the field of longevity research that you’ve come across recently, and why do you find it so compelling?Nothing really. The next big milestone will be a clinical trial that shows extension of maximal life span.  In your opinion, which emerging longevity trend or product will have the most transformative impact on our health over the next five years, and why?Gym, sleep, healthy food - rest is noise for now.One thing you wish more people knew about health and longevity?It's the most important thing in the world.What is the biggest longevity myth you’d like to debunk?Any thing that is available right now is proven to extend maximal life span. If you could recommend only one supplement for a longer, healthier life, which would it be, and what makes it indispensable?Vitamin D, most people have deficiencies. How old can we potentially become at maximum?No limit in theory. At least I'm not aware of any. What resources (books, podcasts, mentors) have been most valuable in your entrepreneurial journey?https://waitbutwhy.com/If there’s one message or insight you’d like readers to take away from your journey, what would it be?Work in Longevity! Focus on impact instead of money. 

Vitamin K for cognition
Cognition

2 min read

Vitamin K for cognition

Vitamin for the mind. Could a simple vitamin found in leafy greens keep your brain sharp with age? New research from Tufts University hints that vitamin K deficiency might speed up mental decline—especially in memory and learning.Key facts & findingsBrain booster: Vitamin K shows up in brain tissue as menaquinone-4, potentially supporting cognitive function.Less K, more problems: Mice lacking vitamin K displayed worse results in tests assessing memory and spatial learning.Hippocampus hit: The vitamin K–deficient group had fewer new neurons in the dentate gyrus, a key region for learning.Inflammation spike: These deficient mice also showed overactive immune cells (microglia), leading to higher brain inflammation.Additional context & expert insightVitamin K is typically found in dark, leafy veggies—like spinach and kale—and is already known for aiding blood clotting. This study suggests it might also protect the aging brain by boosting neuron formation and reducing inflammation. “We’re not telling everyone to go buy supplements,” says the research team, who stress that a balanced diet is the real key. Put differently: your daily salad might do more than keep your arteries clear—it may also keep your mind in top form.Looking aheadScientists plan to dig deeper into the exact mechanisms tying vitamin K to brain health, and possibly see if the same trends hold in humans of all ages. For now, consider upping your veggie intake. Your brain, and maybe your future self, will thank you.

From bloodwork to DNA to AI and back: my journey to solve a micronutrient mystery
Zinc

5 min read

From bloodwork to DNA to AI and back: my journey to solve a micronutrient mystery

How low zinc levels turned into a detective story about health optimization, genetics — and how to use ChatGPT wisely without falling into traps.Hi, I’m Heiko – coach, biohacker, and micronutrient enthusiast. For years, I’ve been fine-tuning my approach to health and longevity by regularly testing my blood for micronutrient levels. Why? Because I believe that keeping all essential and semi-essential micronutrients in the optimal range gives my body the best possible foundation to thrive — mentally, physically, and emotionally.It’s a proactive strategy inspired by experts like Dr. Helena Orfanos-Boeckel, and it’s shaped how I think about performance, stress resilience, and long-term health.One nutrient I’ve been particularly focused on is zinc. And yet — despite consistent, even high-dose supplementation — my blood levels of zinc just won’t budge into the optimal range. Frustrating? Definitely. But also a great opportunity to dig deeper.That’s how this article came about. After a nudge from Sandra (thanks again!) in the New Zapiens community, I decided to revisit my DNA test from SelfDecode. Maybe the answer to my stubbornly low zinc levels was hiding in my genes?Why is zinc so important?Before we dive into the analysis, let’s take a quick detour: zinc is a true multitasker.It plays a key role in the immune system, supports wound healing, and helps fight infections.It’s essential for protein synthesis, making it crucial for muscle growth and recovery.It influences cognitive function, impacting focus and mood.It acts as a cofactor for many enzymes, involved in metabolism, hormone production, and digestion.And here’s a kicker: If you exercise a lot or sweat frequently (sauna, anyone?), you could be losing significant amounts of zinc.Sounds like something you’d want enough of, right? That’s exactly what I thought — but my levels refused to rise ...Checking my DNA test: no red flags?My first glance at my SelfDecode report:SelfDecode resultSo, no increased requirement according to my genetic data. Hmm.But maybe ChatGPT knows more?I asked whether there are SNPs associated with higher zinc needs.(SNPs = Single Nucleotide Polymorphisms, genetic variations that can influence various bodily processes.)ChatGPT provided a first list of potentially relevant SNPs:Screenshot 2025-04-10 175904.png 176.05 KBNever only ask once, especially with ChatGPT ;) So I asked again if there might be some more SNPs that could be relevant. And ChatGPT listed some more:Screenshot 2025-04-10 180441.png 224.03 KBBased on that, I dug into my SelfDecode data and checked my own genetic variations. And I added all the SNP characteristics that SelfDecode had listed as relevant, even if the overall assessment did not reveal an increased need.Then, I asked ChatGPT to interpret all my individual data.Screenshot 2025-04-10 181041.png 59.84 KBThen I asked ChatGPT to critically review its own assessment.Screenshot 2025-04-10 181228.png 17.69 KBSurprise, surprise: ChatGPT’s analysis and conclusion was quite different from SelfDecode’s!While SelfDecode suggested my zinc needs were typical, some SNPs flagged by ChatGPT pointed to a significantly increased requirement!And then I remembered a phrase from the domain of management theory and practice: Culture Eats Strategy for Breakfast.And I asked myself: What if “Lifestyle Eats Genetics for Breakfast”? So what about exercise and sauna for example?I added details about my workout and sauna routine and asked for an updated recommendation.Screenshot 2025-04-10 181433.png 99.79 KBDone? Hmm… not so fast!The trap of question framingAnother shoutout to Sandra, who reminded me that answers by AI models like ChatGPT are highly dependent on how you phrase your questions.So, I reworded the question: Could it be that the original recommendation was way too low in comparison to standard recommendations?Screenshot 2025-04-10 181633.png 148.02 KBThen, I went the opposite way: Was the updated recommendation too high? Maybe ChatGPT simply added up all effects, without considering overlapping factors?Screenshot 2025-04-10 181807.png 157.65 KBNow I had multiple versions of an answer. Which one should I trust?Guess what I did … of course: I asked ChatGPT: “So, first too low, then too high, now low again, ... what can I believe you?” ;)Screenshot 2025-04-10 181946.png 236.65 KBAnd: Screenshot 2025-04-10 182334.png 62.61 KBI totally agree: blood work is not the truth, but the best approach we have!Conclusion: ChatGPT is a great tool — if you know how to ask and how to interpret and challenge its answers Please keep in mind: Everybody and every body is different.My unique lifestyle, diet, and habits can’t (yet) be fully captured by any AI model.And that’s fine with me. I now have enough information to fine-tune my zinc supplementation approach. Taking also my individual experiences and some hints by Chris Masterjohn into account, I will supplement like this:👉 2×15 mg zinc citrate in the early morning👉 25 mg zinc bisglycinate in the later morningTwo highly bioavailable forms, taken as far away as possible from other minerals (esp. copper) that could block absorption or interact directly.Now, it’s all about testing, measuring, and adjusting again.Will my zinc levels finally move? Or are there other aspects that I don’t know yet?To be continued... 😃