95 | id == 95
95 | category_id == 9
95 | category_order == 6
95 | category_name == Longevity
95 | category_color == #C47AC0
95 | slug == sod2-longevity
95 | title == Can Antioxidant Defenses Increase Lifespan? (SOD2)
95 | meta_description == SOD2 helps defend against oxidative stress. What is its role in holding off degenerative disease & increasing lifespan?
95 | summary == <p><strong>SOD2 is a mitochondrial enzyme that helps defend the body from oxidative stress. What is its role in holding off degenerative disease and increasing lifespan? Read on to find out.</strong></p>
95 | overall_score_text == Longevity Score (based on SOD2)
95 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/SOD2.jpg
95 | author_id == 1
95 | author_name == Jasmine Foster
95 | author_title == BSc, BEd
95 | author_order == 36
95 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/Jasmine.jpg
95 | author_intro == <p><strong>Jasmine received her BS from McGill University and her BEd from Vancouver Island University.</strong></p>    <p>Jasmine loves helping people understand their brains and bodies, a passion that grew out of her dual background in biology and education. From the chem lab to the classroom, everyone has the right to learn and make informed decisions about their health.</p>
95 | reviewer == None
95 | medical_reviewer_id == 11
95 | medical_reviewer_name == Puya Yazdi
95 | medical_reviewer_title == MD
95 | publish_date == 2020
95 | publish_date == 2
95 | publish_date == 5
95 | avg_rating == 5.0
95 | tags_id == 179
95 | tags_name == Age-Related Disease
95 | tags_id == 101
95 | tags_name == Longevity
95 | tags_id == 39
95 | tags_name == Oxidative Stress
95 | tags_id == 254
95 | tags_name == SOD2 Gene
95 | permissions_favorite == False
95 | permissions_rate == False
95 | content_article == <h2><span style="font-weight: 400;">The Mitochondrial Antioxidant</span></h2> <p><span style="font-weight: 400;">SOD2 (also called MnSOD) is one of the superoxide dismutase enzymes, alongside SOD1 and SOD3. SOD2 is unique in that it requires manganese (Mn) to work, where the other two need copper and zinc [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811078/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The superoxide dismutase enzyme family transforms superoxide, a powerful oxidative agent, into hydrogen peroxide and oxygen, which are significantly less reactive oxygen species. SOD2 performs this role inside the mitochondria; hydrogen peroxide can then diffuse out of the mitochondria, where it will be further transformed by the cell&rsquo;s antioxidant machinery [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811078/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Thus, SOD2 is a central and essential part of the antioxidant defense mechanisms of the body. Reduced SOD2 activity is associated with increased oxidative stress and degenerative disease [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811078/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">SOD2 is a member of the superoxide dismutase enzyme family. It transforms superoxide into hydrogen peroxide and oxygen in the mitochondria.</span></p> <h3><span style="font-weight: 400;">SOD2, Disease, and Mortality</span></h3> <p><span style="font-weight: 400;">SOD2, and the rs4880 variant, in particular, has been implicated in an impressive number of diseases and medical complications. However, the relationship isn&rsquo;t straightforward; the &lsquo;A&rsquo; allele is more common in people with cardiomyopathy, atherosclerosis, and lung cancer, while the &lsquo;G&rsquo; allele is more common in people with breast, prostate, and colorectal cancers, hypertension, sporadic motor neuron disease, Parkinson&rsquo;s disease, and Alzheimer&rsquo;s disease [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720516/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">One would think that the relationship should be simple: increased SOD2 activity means lower oxidative stress, which should in turn protect against disease. Researchers disagree about why this apparent contradiction exists; some studies have found that temporary increases in oxidative stress have beneficial effects on health. Thus, some researchers have suggested that somewhat reduced SOD2 activity might actually be good in some cases. Research is ongoing [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/11773609"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/18191751"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">The rs4880 variant of SOD2 has been linked to many conditions and diseases. The relationship is complex, with each allele associated with different diseases.</span></p> <h3><span style="font-weight: 400;">Aging &amp; Neurodegeneration</span></h3> <p><span style="font-weight: 400;">Researchers are fairly confident that SOD2 plays an essential role in maintaining the function of neurons both in the brain and in nerves in the rest of the body. In fact, SOD2 seems to be disproportionately important for neurons compared to other types of cells [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811078/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Over the course of our lives, our bodies&rsquo; antioxidant mechanisms decline in efficiency, leading to a gradual decrease in neuron function. Higher SOD2 activity appears to maintain neuron function for longer; some researchers contend that higher SOD2 activity therefore delays neurodegenerative disease [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811078/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Amyotrophic lateral sclerosis (ALS) has a median survival time of 2-3 years, while people with Huntington&rsquo;s disease typically survive another 25 years after diagnosis; however, neurodegenerative diseases are generally fatal, given that the human body cannot survive the destruction of its nervous system [</span><a href="https://jamanetwork.com/journals/jamaneurology/article-abstract/2656830"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">SOD2 protects against neurodegenerative disease, and researchers believe that more SOD2 is better for this purpose.</span></p> <h2><span style="font-weight: 400;">How Does SOD2 Affect Longevity?</span></h2> <p><span style="font-weight: 400;">Two variants in the SOD2 gene have been directly associated with longevity so far. The rs4880 variant has been studied the most intensively, but the results have been complex and somewhat contradictory.</span></p> <p><span style="font-weight: 400;">One study of Danish people born in the year 1905 found that the &lsquo;G&rsquo; allele was more common in the very elderly. However, another study found that the &lsquo;A&rsquo; allele was much more common in very elderly Ashkenazi Jewish men [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720516/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15621215/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Some researchers have suggested that one allele or the other may be more beneficial depending on other genetic and environmental factors [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262222/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><span style="font-weight: 400;">Contradictory Results?</span></h3> <p><span style="font-weight: 400;">Such a complex relationship with longevity also makes sense in the context of other apparently contradictory research on rs4880 and measurements of SOD2 activity and oxidative stress. Some cell studies have found that rs4880-G SOD2 crosses the mitochondrial membrane more easily, leading to higher enzyme activity in the mitochondria. However, a study in humans found that people with rs4880-A had higher SOD2 activity and better protection from oxidative stress [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16538174"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Given all of this apparently contradictory evidence, it&rsquo;s helpful to look at the SOD2 variants&rsquo; relationships with dangerous conditions. The &lsquo;G&rsquo; allele has been associated with more and worse diseases, including cancers, hypertension, and neurodegenerative disorders [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720516/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The &lsquo;G&rsquo; allele has also been linked with noise-induced hearing loss, ear toxicity from cisplatin treatment, infertility, and worse lung damage after phthalate exposure [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19493484"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673994/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://selfhacked.com/app/uploads/2014/12/1-s2.0-S0891584911012196-main.pdf"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/23261794"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">These relationships further support the growing consensus that the &lsquo;G&rsquo; allele confers less protection from oxidative stress than the &lsquo;A&rsquo; allele.</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Despite some contradictory evidence and with some exceptions, the growing consensus is that &lsquo;G&rsquo; is the risk allele of rs4880.</span></p> <h3><span style="font-weight: 400;">A Second SNP</span></h3> <p><span style="font-weight: 400;">While rs4880 gets most of the spotlight in SOD2 research, a second SNP, rs2758331, has also been associated with lifespan. In one study of exceptionally long-lived people in New England, the &lsquo;C&rsquo; allele of rs2758331 was significantly more common in the oldest old than in the general population [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261167/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">This SNP is nowhere near as well-studied as rs4880, and only a single study has investigated its effect on lifespan so far. Furthermore, while the &lsquo;A&rsquo; allele of rs2758331 has been associated with prostate cancer (thereby supporting the idea of a beneficial &lsquo;C&rsquo; allele), the &lsquo;C&rsquo; allele has been associated with liver damage after bisphenol A (BPA) exposure [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664461/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.sciencedirect.com/science/article/abs/pii/S0013935116300688"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Additional research is required to fully untangle the effect of rs2758331 on SOD2 activity and lifespan.</span></p> <h2><span style="font-weight: 400;">Your SOD2 Results for Longevity</span></h2> <p><span style="font-weight: 400;">It&rsquo;s important to note that certain genotypes being associated with longevity doesn&rsquo;t necessarily mean that everyone with that genotype will live an exceptionally long life! Many different factors, including other genetic and environmental factors, are believed to influence longevity.&nbsp;</span></p> <p><span style="font-weight: 400;">Furthermore, keep in mind the complex relationship between SOD2, longevity, and disease in different ethnic groups. If you are not descended from the groups discussed in these studies, the results may not apply to you!</span></p> <p>*5868444056142907*</p> <h3><span style="font-weight: 400;">SNP Summary and Table</span></h3> <p><strong>SOD2 rs4880</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = More common in very elderly Danish people, but less common in very elderly Ashkenazi Jewish men. Decreased SOD2 activity &amp; increased oxidative stress.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Less common in very elderly Danish people, but more common in very elderly Ashkenazi Jewish men. Increased SOD2 activity &amp; decreased oxidative stress.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The growing consensus identifies &lsquo;G&rsquo; as the risk allele, despite the Danish cohort</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">About 20% of all people have the &lsquo;GG&rsquo; genotype</span></li> </ul> <p><strong>SOD2 rs2758331</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = More common in exceptionally long-lived people</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Less common in exceptionally long-lived people</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">About 14% of all people have the &lsquo;AA&rsquo; genotype</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">rs4880-G is disproportionately inherited with rs2758331-A, further supporting the hypothesis that rs4880-G is detrimental.</span></li> </ul> <p>*2175128751972594*</p> <h2><span style="font-weight: 400;">Recommendations to Increase Longevity</span></h2> <p><span style="font-weight: 400;">To avoid any adverse effects or unexpected interactions, always speak with your doctor before making any significant changes to your diet or supplement regimen. None of the recommendations in this section should ever be used in place of what your doctor recommends or prescribes.</span></p> <p>*2190732589093169*</p> <h3><span style="font-weight: 400;">Get a Good Night&rsquo;s Sleep</span></h3> <p><span style="font-weight: 400;">Some researchers have argued that one of the primary biological functions of sleep is to give the body&rsquo;s antioxidant mechanisms time to work, to clear out the reactive oxygen species built up during waking hours. In animal models, increased oxidative stress triggers sleep, and sleep reduces oxidative stress [</span><a href="https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2005206"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In humans, sleep apnea has been linked to oxidative stress and cardiovascular disease. If you have untreated sleep apnea, talk to your doctor about strategies that you can use to manage or treat it [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/23261794"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><span style="font-weight: 400;">Dietary Manganese</span></h3> <p><span style="font-weight: 400;">SOD2 requires manganese to function, so it&rsquo;s important to make sure you get enough manganese in your diet. Higher than average manganese levels were found in the hair of people who lived to a hundred years of age. However, both manganese deficiency and excess manganese have been linked with oxidative stress and degenerative disease. We therefore recommend against manganese supplements unless your doctor recommends them [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037549/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5907490/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Instead, the best way to consume manganese is as part of a healthy diet. The daily recommended intake of manganese is 2.3 mg for men and 1.8 mg for women, with increases to 2.0 mg during pregnancy and 2.6 mg while breastfeeding. The richest sources include whole grains, nuts, seeds, and mollusks (like oysters and mussels) [</span><a href="https://ods.od.nih.gov/factsheets/Manganese-HealthProfessional/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Barring severe dietary restrictions, most people should have no trouble getting enough manganese through their diets.</span></p> <h3><span style="font-weight: 400;">Supplemental Curcumin</span></h3> <p><span style="font-weight: 400;">In fly, mouse, and cell studies, supplemental curcumin increased SOD2 activity and reduced markers of oxidative stress and aging [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/22653297"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557759/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">A meta-analysis of three human trials found that curcumin did not seem to directly increase SOD concentrations. However, curcumin supplementation did measurably decrease malondialdehyde (MDA), a marker of oxidative stress [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/30402990"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Thus, if your DNA indicates low SOD2 activity, supplemental curcumin may help reduce oxidative stress even if it doesn&rsquo;t increase SOD2 directly.</span></p>
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95 | content_learn_more_2175128751972594_text == Based on the variants we looked at, your SOD2 gene variants are associated with an average lifespan. Your extracellular antioxidants may not be functioning optimally; a diet rich in sources of manganese may help support SOD2 function. Read on for more strategies to manage oxidative stress.
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rsIDs = rs4880,rs2758331
rsStatus = rs4880,SOD2,chr6,159692840,A,G,,,17,16,HET
rsStatus = rs2758331,SOD2,chr6,159684038,C,A,,,13,14,HET
