Genetics
Episodes
Dr. Rhonda Patrick covers lithium microdosing, reducing homocysteine, aluminum's link to cancer, and beta-alanine and alpha-lipoic acid supplements.
Dr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.
Dr. George Church discusses revolutionary technologies in the field of genetic engineering.
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Exercise Biomarkers Vitamin E Genetics Eyes Caffeine Folate Sulforaphane Sauna Antioxidant Dairy Polyphenol Supplements Wearable TechnologyDr. Rhonda Patrick covers lithium microdosing, reducing homocysteine, aluminum's link to cancer, and beta-alanine and alpha-lipoic acid supplements.
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Dr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.
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Dr. George Church discusses revolutionary technologies in the field of genetic engineering.
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In this clip, Dr. Ronald Krauss describes why it may be more beneficial to reduce LDL levels than to raise HDL levels.
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Mendelian randomization, a powerful tool to assess the effects of low vitamin D | Roger Seheult ClipIn this clip, Dr. Rhonda Patrick describes what Mendelian randomization studies are and how they are valuable instruments in the scientific toolbox.
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In this clip, Dr. Steve Horvath describes research suggesting that caloric restriction, especially when it is reversing obesity or metabolic syndrome, may slow epigenetic aging.
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In this clip, Dr. Steve Horvath discusses whether epigenetic clocks play causal roles in aging.
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Methylation and demethylation are critical processes in development and interfering with the enzymes that carry out these two opposing processes can play critical roles in epigenetic age.
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Some epigenetic clock evidence reinforces the idea that accelerated aging may be a consequence of chronic inflammation.
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As techniques are developed to differentiate and transdifferentiate cells from one cell type, such as a fibroblast, into another, such as a neuron, interesting patterns of effects on epigenetic age are revealed.
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A study using a mouse model of premature aging showed that short-term expression of four special factors which reverse epigenetic age ameliorated cellular and physiological hallmarks of aging and prolonged lifespan.
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Scientists have observed that the epigenetic clock of transplanted cells and their descendant lineages synchronize with the donor rather than the recipient, a fascinating phenomenon that offers promise for the idea of rejuvenation in humans.
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In this clip, Dr. Steve Horvath discusses how epigenetic aging differs from senescence-mediated aging.
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How epigenetic predictions align with onset of cancer, Parkinson's and Alzheimer's | Steve Horvath ClipA person's epigenetic age correlates with their risk for developing major diseases of aging like cancer, Alzheimer's disease, and Parkinson's.
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The stability of methylation patterns on DNA samples means the data can be trusted more in the lab when investigating anti-aging interventions.
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Horvath epigenetic aging clocks measure two types of age: biological aging vs. chronological aging ClipIn this clip, Dr. Steve Horvath explains the differences between chronological age and biological age.
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Evidence indicates that the heritability of epigenetic aging is about 40 percent. This is seen in supercentenarians and their offspring, who tend to age slower than their younger counterparts.
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Dr. Steve Horvath discusses epigenetic aging clocks and their use in predicting biological aging and healthspan.
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Dr. Steve Horvath found a way to measure biological aging – a type of "clock" – based on the methylation pattern of an organism's genome. This video primer explains the basics of epigenetic clocks, the topic of our interview with Dr. Steve Horvath.
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In this clip, Dr. Giselle Petzinger highlights some of the risk factors for Parkinson's disease, and discusses how this is likely a multifaceted problem.
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In this clip, Dr. Rhonda Patrick discusses the role that genetics plays in the immune system.
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COVID-19 Vitamin D Nutrition Exercise Microbiome Sleep Vitamin C Omega-3 Inflammation Immune System Virus Micronutrients Vitamin E Vaccine Genetics Testosterone Estrogen Zinc Fiber AutoimmunityCOVID-19 Q&A Part 2: Rhonda Patrick, Ph.D. answers subscriber questions in a multi-part series.
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In this clip, Tim Ferriss discusses his MTHFR status and his experience with vitamin supplementation.
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Rhonda explains NAD+: importance for aging, decline with age, boosters (nicotinamide riboside, nicotinamide mononucleotide), and data in animals and humans.
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In this clip, Dr. David Sinclair describes the major breakthroughs in aging research and the unique relationships that develop between researchers and the organisms they study.
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Dr. David Sinclair on Informational Theory of Aging, Nicotinamide Mononucleotide, Resveratrol & MoreDr. David Sinclair discusses the mechanisms that drive human aging and the importance of identifying ways to slow or reverse aging's effects.
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In this clip, Dr. Roland Griffiths and Dr. Rhonda Patrick discuss the effects of meditation on gene expression.
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Dr. Elissa Epel describes how pre-pregnancy parental health impacts offspring.
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Dr. Elissa Epel describes the effects of longer sperm telomere length on subsequent generations.
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Dr. Rhonda Patrick and Dr. Elissa Epel describe the factors that influence how we respond to diet.
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Telomeres explained: role in genomic stability, stem cells, replicative senescence | Elissa Epel ClipDr. Elissa Epel gives a brief overview of telomeres and the enzyme telomerase and explains how they impact health and lifespan.
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Dr. Elissa Epel explains how aging syndromes can be passed to offspring via epigenetic mechanisms.
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Rhonda Nutrition Exercise Alzheimer's Aging Fasting Memory Genetics Mortality Sauna Time-Restricted Eating Cardiovascular Supplements Ketogenic DietDr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.
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Epigenetics Vitamin D Nutrition Exercise Aging Metabolism Sleep Diabetes Telomeres DNA Damage Stem Cells Stress Melatonin Vitamin E Genetics 23andMe Heat Stress Autophagy Autism Folate Sauna AntioxidantOur genes influence the way we absorb and metabolize micronutrients. Nutrigenomics looks at the influence genetic variation has over micronutrient absorption/metabolism and the biological consequences of this dynamic relationship.
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Dr. Rhonda Patrick talks about transgenerational effects of caloric restriction on longevity, B-vitamins silencing bad genes, cognitive stimulation reversing neurodegenerative disease, exercise increases neurogenesis, and ways in which vitamin D might influence aging.
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This video breaks down, point-by-point what gene polymorphisms you might look at, and how they relate to very specific micronutrients.
Topic Pages
News & Publications
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Even if you work out, spending most of your day sitting may still adversely affect your health in ways that don’t become apparent until later in life. A recent study found that 35-year-olds who engaged in 30 minutes of vigorous exercise each day had cholesterol levels comparable to those of sedentary 30-year-olds, suggesting that vigorous exercise can offset up to five years of age-related decline in heart health.
Researchers analyzed data from adults aged 28 to 49 who participated in the Colorado Adoption/Twin Study of Lifespan Behavioral Development and Cognitive Aging. They tracked the time participants spent sitting each day and how often they engaged in moderate or vigorous physical activity. To isolate the effects of behavior from shared genetics and environment, the researchers also compared identical twins with differing activity and sitting patterns. They examined two key health markers: body mass index and the ratio of total to high-density lipoprotein cholesterol—a strong predictor of heart disease risk.
They found that people who spent more time sitting tended to have higher body mass index and worse cholesterol ratios as they aged. However, among those who sat for the same amount of time—about four hours daily—participants who exercised vigorously for at least 30 minutes daily had cholesterol profiles that resembled those of people five years younger. In some cases, vigorous activity was associated with health markers typical of people up to 10 years younger, but the protective effect weakened with longer sitting durations. In other words, exercise helped—but only to a point.
These findings suggest that while vigorous exercise offers clear benefits, reducing sitting time is just as important for maintaining good health. “Exercise snacks” can offset the harmful effects of prolonged sitting. Learn more in this clip featuring Dr. Rhonda Patrick and Brady Holmer.
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While genes play a role in aging, lifestyle and environmental exposures—collectively called the exposome—may have a more robust effect on aging and longevity. A recent study found that the exposome contributes far more to premature death and age-related diseases than genetic risk alone.
Researchers analyzed data from nearly 500,000 people enrolled in the UK Biobank to measure the exposome’s role in aging. They identified environmental exposures linked to early death and biological aging, then used a proteomic age clock—a tool that tracks molecular signs of aging—to confirm which exposures accelerate the aging process. Finally, they compared the exposome’s influence on disease risk to that of genetic predisposition.
The exposome explained 17 percentage points more of the variation in mortality than genetic risk, which accounted for less than two percentage points. It was more strongly connected to lung, heart, and liver diseases, while genetic factors were more closely associated with certain cancers and dementias. The analysis identified three disease states and 22 biomarkers related to liver and kidney function, cardiovascular and metabolic health, inflammation, longevity, genetics, and vitamin and mineral status that independently drive biological aging and disease risk.
These findings suggest that the exposome is critical in shaping health and longevity. While genes contribute to some diseases, environmental exposures throughout life greatly influence aging and survival. Air pollution is an exposome element contributing to disease and early death. Learn how wearable devices measure the air pollution exposome in this episode featuring Dr. Michael Snyder.
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Donating blood is an act of generosity that saves lives, yet few donors think about how it affects their own health. Each donation triggers a surge in blood cell production, a process that could subtly shape the long-term health of blood-forming stem cells. A recent study found that frequent blood donation promotes the expansion of specific blood stem cell mutations that support healthy red blood cell production.
Researchers analyzed blood samples from 217 older men who had donated more than 100 times and compared them to 212 men who had donated fewer than 10 times. They looked for clonal hematopoiesis, a condition where blood stem cells acquire genetic changes that allow specific cell populations to expand. They also used gene-editing techniques to study how particular mutations behaved when exposed to erythropoietin, a hormone that increases after blood loss.
They found that the overall rate of clonal hematopoiesis was similar between frequent and infrequent donors. However, mutations in the DNMT3A gene showed distinct patterns in frequent donors. Some of these mutations responded to erythropoietin by expanding, while others, known to be associated with leukemia, were more likely to grow in response to interferon-gamma, a protein involved in the immune response. Further analysis revealed that the erythropoietin-responsive mutations tended to push blood stem cells toward making more red blood cells rather than leading to abnormal or harmful changes.
These findings suggest that repeated blood donation encourages the expansion of specific blood stem cell mutations, but the effects support normal blood cell production rather than increase disease risk. Blood donation also lowers levels of iron—a key nutrient that, in excess, harms the brain. Learn more in this episode featuring Dr. Gordon Lithgow.
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Higher folate levels during pregnancy may protect against lead's neurotoxic effects, potentially reducing risk of autism-like behaviors in children. ehp.niehs.nih.gov
Lead exposure during pregnancy can harm a child’s developing brain, increasing the risk of autism-related behaviors. Some evidence suggests that folate, a B vitamin, might help protect against lead’s neurotoxic effects. A recent study found that higher folate levels during pregnancy may help reduce the risk of autism-like behaviors in children exposed to lead before birth.
Researchers analyzed data from a large mother-infant cohort study that tracked participants from pregnancy through early childhood. They measured blood lead levels and plasma folate concentrations during the women’s first and third trimesters. They assessed the children for autism-related behaviors when they were three to four years old. They also examined whether folic acid supplementation and MTHFR, a maternal genetic variant influencing folate metabolism, affected these associations.
They found that third-trimester blood lead levels were associated with more autism-like behaviors in children whose mothers had low third-trimester folate levels. They did not observe this association among mothers with higher folate levels. Additionally, folic acid supplementation appeared to reduce the harmful effects of lead exposure. The MTHFR genetic variant influenced the findings, but the effects were not statistically significant.
These findings suggest adequate folate levels during pregnancy may help protect against the neurodevelopmental harm linked to prenatal lead exposure.
Folate is the natural form of vitamin B9 found in foods, while folic acid is the synthetic form used in supplements and fortified foods. Folic acid has higher bioavailability, meaning the body more readily absorbs it than naturally occurring folate. Learn more about folate in this clip featuring Dr. Bruce Ames.
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Omega-3 fatty acids reduce inflammation and disease activity in rheumatoid arthritis and lupus—according to an umbrella review of 21 analyses. www.sciencedirect.com
Autoimmune diseases occur when the body mistakenly attacks its own tissues, driving chronic inflammation and tissue damage. However, evidence suggests that omega-3 fatty acids may benefit people with autoimmune diseases. A recent study found that omega-3s help reduce disease severity in rheumatoid arthritis and lupus but are less effective against other autoimmune disorders.
Researchers conducted an umbrella review to summarize findings from 21 systematic reviews and meta-analyses on the effects of omega-3s on autoimmune diseases. They also used Mendelian randomization—a method that leverages genetic data to identify causal relationships—to explore further whether omega-3s directly influence the risk of developing autoimmune diseases.
They found that omega-3s were associated with reduced inflammation and disease activity in people with rheumatoid arthritis and lupus. However, they found no clear evidence of omega-3s' effects on other autoimmune diseases, including multiple sclerosis, type 1 diabetes, or Crohn’s disease. The quality of evidence varied, with one high-quality study and several moderate or low-quality studies.
These findings suggest that omega-3 fatty acids benefit people with certain autoimmune disorders, but their effects vary across different conditions. Omega-3 fatty acids exert robust anti-inflammatory properties due to their formation of specialized pro-resolving molecules (SPMs), a broad class of metabolites that resolve inflammation. Learn more about SPMs in this clip featuring Dr. Bill Harris.
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Just 1.5 teaspoons of olive oil daily reduces the risk of death from dementia by 28%, regardless of genetic factors. jamanetwork.com
What we eat and drink can profoundly affect our disease risk as we age. A recent study found that consuming just 1.5 teaspoons of olive oil daily can reduce the risk of death from dementia by 28%, even among APOE4 carriers, a potent genetic risk factor for dementia.
Researchers asked more than 92,000 healthy, middle-aged adults about their olive oil consumption over a 28-year period. They conducted genetic analyses to determine whether the participants carried the APOE4 gene. Then, using national death records, they ascertained which of the participants died of dementia.
They found that more than 4,700 of the participants died of dementia during the study period. People who carried one APOE4 allele were roughly twice as likely to die from dementia; those with two APOE4 alleles were five to nine times more likely. However, people who consumed 7 grams or more of olive oil daily—roughly 1.5 teaspoons—were 28% less likely to die of dementia than those who didn’t consume olive oil, regardless of their APOE4 status. Replacing 5 grams (about a teaspoon) of margarine or mayonnaise with an equivalent amount of olive oil reduced the risk of death from dementia by as much as 14%.
These findings suggest that eating olive oil markedly reduces the risk of death from dementia. Olive oil contains healthy fats and polyphenols—bioactive compounds with potent antioxidant and anti-inflammatory properties. Learn more about polyphenols in our overview article.
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Genes play critical roles in determining how long a person lives, but a new study suggests that the secret to longevity may be as simple as “food as medicine.” Centenarians—people who live 100 years or more—typically eat healthy, balanced diets and require fewer medications than their shorter-lived peers.
Researchers analyzed studies examining the lifestyles, medication use, and overall health of centenarians and near-centenarians aged 95 to 118. Their analysis included 34 studies and involved more than 59,000 participants.
They identified several healthy lifestyle habits of long-lived adults: Engaging in regular physical activity Avoiding alcohol and tobacco Adhering to a diverse, macronutrient-balanced diet Preferring less salty foods Using few medications—with just over four taken daily, primarily blood pressure medicines or other cardiovascular drugs
Multiple drug use—known as polypharmacy—is common in older adults. Defined as taking more than five medications daily, polypharmacy is linked with many adverse health effects, especially among older adults, who are at risk of a “prescription cascade”—where the side effects of drugs can be misdiagnosed as symptoms of another disease, creating a vicious cycle of more drug use.
This analysis suggests that using food as medicine—through healthy, balanced diets—combined with lower drug use contributes to healthy aging and longevity. Learn how other healthy lifestyle behaviors like exercise and dietary supplementation also promote longevity in this episode featuring Dr. Rhonda Patrick.
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Lifestyle interventions that focus on diet, exercise, and weight management reduce the risk of diabetes—despite underlying genetic risk. pubmed.ncbi.nlm.nih.gov
Although a person’s genes play a pivotal role in whether they develop diabetes, lifestyle factors—like diet, exercise, and body weight—influence their risk, too. A recent study found that lifestyle interventions reduce the risk of developing diabetes, especially among those at high genetic risk.
The study involved nearly 1,000 middle-aged men with metabolic syndrome—a constellation of health conditions that increases the for diabetes. About half of the men had a low genetic risk for the disease, while the remainder had a high genetic risk. The men participated in a three-year-long group-based lifestyle intervention program that involved dietary counseling, exercise guidance, and weight management. Researchers monitored the men’s health and diabetes incidence throughout the study period.
They found that the intervention reduced the risk of developing diabetes by 70% among participants with high genetic risk and 31% among those with low genetic risk. However, the latter reduction wasn’t statistically significant. The intervention promoted weight loss and prevented increased blood glucose levels in both groups.
These findings suggest that lifestyle interventions can have marked effects on diabetes incidence in people at risk. Exercise, in particular, makes the body’s tissues more sensitive to insulin, helping to maintain healthy blood glucose levels. Learn more about how exercise may prevent diabetes in this episode featuring Dr. Guido Kroemer.
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Genetics plays a key role in the body's response to exercise. scitechdaily.com
Many factors influence the extent to which exercise promotes weight loss, including exercise intensity, dietary habits, and overall lifestyle. Evidence suggests genetic differences play a role, too. A recent study found that mice with certain variants of PGC1-alpha—a key regulator of metabolism—consume less oxygen and burn less fat during workouts and are more likely to gain weight despite increased activity.
Researchers analyzed gene expression in mice to determine the distribution of the three variants of PGC1-alpha: A, B, and C. Then, they assessed the animals' muscle growth, fat burning, and oxygen consumption during rest, short-term exercise, and long-term exercise. They performed the same assessments on 20 men, half of whom had type 2 diabetes.
They found that although the three variants have similar functions, the A variant is widely distributed throughout the body, but the B and C variants are primarily found in brown adipose tissue, skeletal muscle, and the heart. They found that mice lacking the B and C variants had a diminished response to exercise, consuming less oxygen and burning less fat. These mice gained weight, developed high insulin levels, and were intolerant of cold temperatures. Men who had higher expression of the B and C variants consumed more oxygen and had less body fat, even among those with type 2 diabetes.
These findings suggest that variants of PGC1-alpha influence the body’s response to exercise and highlight potential strategies for treating obesity.
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Omega-3 and omega-6 fatty acids reduce lipoprotein(a) levels in healthy men, influencing cardiovascular disease risk. www.atherosclerosis-journal.com
Lipoprotein(a) [Lp(a)] is a type of low-density lipoprotein (LDL). High Lp(a) levels increase a person’s risk for atherosclerosis, heart disease, and stroke. A recent study found that alpha-linolenic acid (ALA) and linoleic acid (LA) both reduce Lp(a) concentrations in healthy men, but ALA is more effective at lowering cholesterol.
The study involved 130 men enrolled in an ongoing cohort study in Finland. Researchers provided the participants with diets enriched in either ALA, an omega-3 fatty acid, or LA, an omega-6 fatty acid, for eight weeks.
They found that serum Lp(a) concentrations dropped 7.3% among those who ate the ALA-rich diet and 9.5% among those who ate the LA-rich diet. Reductions were greater among those with higher baseline Lp(a) concentrations. However, those who ate the ALA diet experienced greater reductions in LDL cholesterol, apolipoprotein B, and other cholesterol components. Whether the participants carried the FADS1 rs174550 genotype did not influence their response to the diets.
The FADS1 rs174550 is a genetic variant that influences the body’s ability to convert certain fatty acids. This variant can affect how efficiently omega-3 and omega-6 fatty acids are metabolized, potentially influencing lipid levels and overall health.
These findings suggest that ALA and LA exert similar Lp(a)-lowering effects, but ALA may be more effective at lowering cholesterol and other atherogenic factors. Learn more about Lp(a) in this Q&A featuring Dr. Rhonda Patrick.
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Higher-dose omega-3 supplementation elevates blood levels, even in Alzheimer’s high-risk APOE4 carriers, but obesity may hinder its brain availability. content.iospress.com
Omega-3 fatty acids play critical roles in maintaining brain health and function, potentially reducing the risk of developing Alzheimer’s disease. People who carry the APOE4 gene variant and those with obesity have a higher risk of developing the disease, suggesting that differences in metabolism could be a factor. A 2022 study found that obesity influenced the amount of omega-3 in plasma phospholipid form that is important for brain transport.
Fifty people (half of whom carried the APOE4 gene) took 2.5 grams of combined docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) daily for six months. Because omega-3 fatty acids must be in the free fatty acid form or phospholipid form to cross the blood-brain barrier, researchers measured these forms of the fatty acids in the participants' plasma before and after the intervention. They also investigated whether APOE genotype or body mass index (BMI, a proxy for overweight and obesity) influenced these measures.
They found that supplemental omega-3s increased by up to fourfold in all participants, regardless of APOE status. However, participants with a high BMI experienced lower plasma phospholipid omega-3 increases than those with a low BMI. Having a high BMI is a well-established risk factor for Alzheimer’s disease. Interestingly, APOE4 did not influence the amount of plasma phospholipid omega-3.
They also lend support to evidence suggesting that APOE4 carriers do not respond to lower dose omega-3 supplementation as well as non carriers possibly because they do not transport DHA in free fatty acid form across the blood-brain barrier as well. However, the transport of the phospholipid form of DHA across the blood-brain barrier bypasses the default in tight junctions, potentially providing a better means of DHA transport for people with the APOE4 gene and lowering their risk of developing the disease. Learn more about APOE4 and DHA transport in this peer-reviewed article by Dr. Rhonda Patrick.
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Higher vitamin D levels are linked to 18 percent lower dementia risk in older adults with prediabetes. pubmed.ncbi.nlm.nih.gov
Lifestyle and nutritional factors influence the risk of dementia, particularly among people with prediabetes – a condition characterized by elevated blood sugar levels that are not high enough to be classified as diabetes. A recent study found that higher vitamin D levels may reduce the risk of developing dementia in older adults with prediabetes.
Researchers drew on data collected from a large cohort of more than 34,000 older adults enrolled in the UK Biobank, all of whom had prediabetes but did not have dementia at the start of the study. They measured the participants' blood vitamin D levels and monitored them for the development of dementia, including Alzheimer’s disease and vascular dementia, for approximately 12 years. Their analysis also considered genetic variations that could influence the relationship between vitamin D levels and dementia risk.
They found that participants with higher blood vitamin D levels were 18 percent less likely to develop any type of dementia, with similar findings for Alzheimer’s disease and vascular dementia. The protective effect of vitamin D was particularly robust in participants who did not carry polymorphisms (genetic variants) related to the vitamin D receptor, highlighting a potential interaction between genetics and vitamin D levels in dementia risk.
These findings suggest that maintaining adequate levels of vitamin D benefits brain health, especially in older adults with prediabetes, a group at elevated risk for dementia. They add to the growing body of evidence supporting the importance of vitamin D for overall health and emphasize the need for further research to understand the mechanisms behind its protective effects on the brain. Learn more about vitamin D in our comprehensive overview article.
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A new study reveals genetic influence on omega-3 metabolism in Hispanic Americans. www.sciencedaily.com
Omega-3 fatty acids are essential in human health, influencing multiple organ systems and physiological responses. However, a person’s omega-3 status varies depending on several factors, including their genetic makeup. A new study shows that genetic differences influence how Hispanic Americans metabolize omega-3s.
Researchers conducted a genome-wide association study, a type of observational study that searches the genome for minor variations in people’s DNA within a particular population. Their analysis included more than 1,400 Hispanic Americans and more than 2,200 African Americans.
They found that the two groups shared many genetic similarities regarding omega-3 metabolism with European Americans. However, they also identified distinct differences, some influencing how Hispanic Americans metabolize omega-3s. Most of these differences occurred in the FADS region on chromosome 11. FADS (fatty acid desaturase) is a gene that encodes a family of enzymes that convert saturated fatty acids into unsaturated and polyunsaturated fatty acids.
These findings provide a better understanding of the genetics underlying omega-3 fatty acid metabolism in diverse genetic groups and underscore the importance of considering ancestry in genetic studies. Learn more about how genetic differences influence nutritional status in this episode featuring Dr. Rhonda Patrick.
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Longevity study reveals key blood markers increase chances of living to 100 and beyond. www.sciencealert.com
By the year 2050, the number of centenarians – people who are 100 years or older – is expected to increase fivefold. Many factors promote centenarians' extraordinary longevity and likely involve the interaction of both lifestyle and genetic variables. A recent study has found that the blood of centenarians differs from their younger counterparts.
The study followed more than 44,000 people from their mid-60s to late 90s until they died. Of these, 1224 of them lived to 100 years old. Using blood samples collected earlier in the participants' lives, researchers assessed 12 blood-related biomarkers previously associated with aging or early death, including those associated with inflammation and indicators of malnutrition, anemia, and liver, kidney, and metabolic function.
They found that higher levels of total cholesterol and iron and lower levels of glucose, creatinine, uric acid, and several enzymes involved in metabolism increased the likelihood of reaching 100 years. Notably, centenarians exhibited strikingly consistent biomarker profiles, even from age 65 and beyond, displaying more favorable values than their shorter-lived counterparts.
Centenarians often carry genetic variants called single-nucleotide polymorphisms associated with longevity. They tend to develop disease much later in life than people of average age span, a phenomenon called “compression of morbidity,” and have longer telomere lengths than adults two to three decades younger. The highest concentrations of centenarians worldwide live in Okinawa, Japan; Sardinia, Italy; Nicoya, Costa Rica; Ikaria, Greece; and Loma Linda, California.
The findings from this study demonstrate that biomarkers related to various genetic or lifestyle influences may contribute to greater longevity. Inflammation also plays a role in longevity. Learn more in this clip featuring Dr. Valter Longo.
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Genes involved in muscle function, energy production and utilization, and oxygen delivery play critical roles in how exercise boosts VO2 max. bmcgenomics.biomedcentral.com
VO2 max – the maximum rate of oxygen a person can consume during exercise – is a robust predictor of a person’s risk for chronic diseases and death. Exercise increases VO2 max, but how well a person responds to exercise training varies considerably and may be influenced by genetics. A 2017 systematic review identified nearly 100 genes that likely influence a person’s VO2 max response to exercise training.
Researchers reviewed 35 studies investigating genetic variants in the context of supervised aerobic exercise interventions aimed at improving VO2 max. The studies were based on DNA samples from more than 4,200 people of varied genetic makeup.
The researchers' analysis identified 97 genes that might influence a person’s VO2 max response to exercise training by modulating muscle function and efficiency, electrolyte balance, lipid metabolism, oxidative phosphorylation, energy production, and oxygen delivery. They found that people who responded more favorably to exercise training tended to have more positive response alleles – genetic variants associated with a more favorable or beneficial response to exercise training – in those genes.
These findings highlight the influence of specific genetic variants on a person’s response to exercise training and their effect on VO2 max improvements. However, the authors cautioned that while most of the articles reviewed in their analysis primarily investigated a single or a limited number of candidate genes or markers, exercise-related traits are intricate and influenced by multiple genes working in concert. Learn how Tabata, a type of HIIT, increases VO2 max in this clip featuring Dr. Martin Gibala.
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Greater lean muscle mass linked to a 12 percent reduction in Alzheimer's disease risk, suggesting exercise can play a critical role in prevention. medicalxpress.com
A growing body of evidence links excess body fat to an increased risk for Alzheimer’s disease, likely due to several factors, including heightened inflammation, insulin resistance, and elevated levels of amyloid-beta (a pathological hallmark of the disease) in fat tissue. A recent study found that greater lean muscle mass reduced the risk for Alzheimer’s disease by 12 percent.
Using Mendelian randomization techniques, researchers analyzed health data and cognitive performance of more than a million people with or without Alzheimer’s disease. Mendelian randomization is a research method that provides evidence of links between modifiable risk factors and disease based on genetic variants within a population. They calculated the participants' muscle mass based on genetic factors, often referred to as genetic proxies.
They found that people with greater genetically proxied lean muscle mass in the arms and legs were 12 percent less likely to develop Alzheimer’s disease, even when accounting for genetic factors that may influence risk. They also demonstrated better cognitive performance.
These findings suggest that lean muscle mass protects against Alzheimer’s disease. However, the researchers noted that whether increasing lean muscle mass can reverse the pathology of Alzheimer’s disease in people with preclinical disease or mild cognitive impairment is unclear. Learn how resistance training helps build and maintain lean muscle mass in this clip featuring Dr. Brad Schoenfeld.
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DHA-rich diet protects against memory deficits and loss of smell in Alzheimer's-prone APOE4 mice, reveals new study. link.springer.com
A diminished or lost sense of smell is a common feature of the early stages of Alzheimer’s disease and other forms of dementia. But a new study in mice that carry the APOE4 gene variant, the primary genetic risk factor for Alzheimer’s disease, shows that DHA – a type of omega-3 fatty acid found in fish – protects against these losses. APOE4-carrying mice that ate a DHA-rich diet retained their sense of smell and the ability to distinguish between objects based on their scent.
Researchers fed normal mice and APOE4 carriers a regular diet or one supplemented with DHA. Then, using MRI scans, they assessed the animals' brain structures and studied their behavior related to smell and the recognition of new objects. They also measured biomarkers related to cell death and inflammation.
They found that the APOE4-carrying mice given a regular diet exhibited memory deficits and difficulty adjusting to new smells and distinguishing between different objects. In addition, their brains showed increased signs of inflammation in the olfactory bulb – the area responsible for the sense of smell. However, APOE4-carrying mice that ate the DHA-rich diet did not exhibit these characteristics.
These findings suggest that a DHA-rich diet benefits APOE4 carriers. Learn more about the beneficial effects of DHA in our comprehensive omega-3 overview article.
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Could omega-3 counteract diseases of aging through epigenetic modification of the IL-6 promoter? www.ncbi.nlm.nih.gov
Higher omega-3 fatty acid consumption could play a unique role in mitigating chronic inflammation by altering the methylation pattern of the interleukin-6 (IL-6) promoter, reducing the activity of this inflammatory cytokine. This epigenetic mechanism highlights omega-3’s capacity to govern gene expression and shape the genetic landscape, transcending its contributions to cell membrane dynamics or mediator production and positioning its effects at the molecular blueprint level rather than merely fine-tuning cellular responses.
The relationship between IL-6 and human health is multifaceted: Interleukin-6 serves as a critical component of the immune response by mediating the acute phase response and fostering beneficial outcomes such as insulin sensitization after exercise. However, when chronically elevated, it can also contribute to age-related chronic diseases.
Chronic immune activation is increasingly recognized as a powerful contributor to the aging process. Developing safe and effective strategies to counteract this persistent activation, which intensifies with age, is essential for promoting healthy aging. However, given that IL-6 also plays a role in healthy physiological functions, pharmacological interventions targeting its action overtly may lead to unintended side effects over time.
A pivotal 2015 study emphasizing the epigenetic effects potentially triggered by increased omega-3 consumption involved over 800 participants from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). This investigation explored the interplay between genetic factors and dietary changes in influencing inflammatory markers in the blood. Researchers analyzed blood samples to assess various inflammatory markers, methylation levels, and omega-3 concentrations.
Results demonstrated that individuals with higher concentrations of omega-3s, particularly docosahexaenoic acid (DHA) derived from fatty fish, exhibited lower IL-6 levels and reduced methylation of the IL-6 promoter at a CpG site called cg01770232. This association between lower methylation levels of the IL-6 promoter and reduced circulating IL-6 emphasizes the significance of omega-3s in mitigating chronic inflammation through DNA epigenetics, which may have a profound cumulative impact on human health over time and possibly even longevity.
DNA methylation is a natural biochemical process that modifies the activity of a DNA segment without altering its sequence, ultimately regulating gene expression. Interleukin-6 is a pro-inflammatory cytokine that is induced in response to infection, trauma, or other disease states. Elevated IL-6 levels have been linked to poor clinical outcomes in cardiovascular disease and an increased risk of premature death from all causes in older adults.
It is worth noting that some individuals carrying a specific genetic variant of IL-6 did not experience the same methylation changes from omega-3 consumption, which suggests that the genetic makeup of some individuals may influence the degree of beneficial physiological response to omega-3s within certain biological domains.
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Time-restricted eating activates genes involved in metabolism and autophagy. www.sciencedaily.com
Time-restricted eating influences the activation of roughly 70 percent of all genes in mice, a new study shows. Mice that ate on a time-restricted schedule had fewer active genes involved in inflammation and oxidative stress and more active genes involved in metabolism and autophagy – a cellular defense mechanism.
Researchers fed two groups of mice a Western-style diet, which is high in fat and sugars, for seven weeks. One group was allowed to eat whenever they chose to, but the other group was allowed to eat only during a nine-hour window each day. At the end of the seven-week intervention, the researchers analyzed gene activity in the animals' tissues at different times of the day.
They found that time-restricted eating altered the activity of more than 80 percent of genes involved in protein synthesis, folding, and maintenance. They also found that time-restricted eating altered amino acid, fat, and glucose metabolism and re-aligned the circadian rhythms of the animals' organs.
These findings suggest that time-restricted eating influences gene activity in mice. If the findings translate to humans, they could have far-reaching implications for chronic metabolic disorders, neurodegenerative diseases, cancer, and other diseases. Learn more about the health benefits of time-restricted eating in this episode featuring Dr. Satchin Panda, the senior investigator for this study.
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Newly identified APOE4 gene variant cuts Alzheimer's disease risk – rather than increasing it. jamanetwork.com
People who carry a newly identified variant of the APOE4 gene are more than 50 percent less likely to develop Alzheimer’s disease than non-carriers, a new study shows. Carriers of an APOE3 variant are more than 60 percent less likely to develop the disease.
Researchers analyzed the genetic makeup of more than 544,000 people. The participants included people who had been diagnosed with Alzheimer’s disease, those with a first-degree relative who had the disease, and those who were healthy.
The researchers found that two rare variants reduced the participants' risk of developing Alzheimer’s disease. Carriers of an APOE4 variant called R251G were 56 percent less likely to develop the disease, and carriers of an APOE3 variant called V236E were 63 percent less likely.
APOE is a protein involved in lipid transport. There are three known forms of the APOE gene that influence Alzheimer’s disease risk: APOE2, APOE3, and APOE4. APOE4 is the primary genetic risk factor for Alzheimer’s disease. Having one APOE4 allele typically increases a person’s Alzheimer’s disease risk as much as threefold; carrying two APOE4 alleles typically increases a person’s risk as much as 15-fold. However, this newly identified sub-type of APOE4 markedly alters that risk and adds complexity to discussions about the role of genetics in Alzheimer’s disease.
These findings suggest that some variants of the APOE gene may be protective against Alzheimer’s disease. Although genetics play key roles in Alzheimer’s disease risk, lifestyle does, too. Eating a healthy diet, exercising, meditating, and sauna use may forestall or even prevent the onset of the disease. Learn more about preventing Alzheimer’s disease in this episode featuring Dr. Dale Bredesen.
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Common estrogen receptor genotype may double HDL cholesterol increase in response to estrogen therapy in postmenopausal women. (2002) www.sciencedaily.com
From the article:
In an analysis of 309 women with heart disease who took hormone replacement therapy or placebo, Herrington found that women with a common mutation in the estrogen receptor alpha gene had dramatic increases in high-density lipoprotein (HDL), or the “good” cholesterol.
“The increase in HDL was more than twice as much as in women without the gene variant,” said Herrington.
[…]
Herrington found that 18 percent of women had a genetic predisposition to high levels of HDL cholesterol when taking estrogen. The HDL increase was dramatic – it was two or three times what is normally achieved with cholesterol drugs used to raise HDL.
From the publication:
Postmenopausal women with coronary disease who have the ER-α IVS1–401 C/C genotype, or several other closely related genotypes, have an augmented response of HDL cholesterol to hormone-replacement therapy.
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Estrogen fluctuations may trigger atypical hippocampal working memory function in women with a BDNF genotype present in one in four women. (2017) www.sciencedaily.com
From the article:
The findings may help to explain individual differences in menstrual cycle and reproductive-related mental disorders linked to fluctuations in the hormone. They may also shed light on mechanisms underlying sex-related differences in onset, severity, and course of mood and anxiety disorders and schizophrenia, which are often marked by working memory deficits. The gene-by-hormone interaction’s effect on circuit function was found only with one of two versions of the gene that codes for BDNF [Val66Met genotype] (brain-derived neurotrophic factor), a chemical messenger operating in the circuit. This version occurs in about a fourth of white women.
The researchers experimentally manipulated estrogen levels over several months in healthy women with both versions of the gene while monitoring their brain activity as they performed a working memory task. When exposed to estrogen, an area in the brain’s memory hub that is typically suppressed during such tasks instead activated in those with the uniquely human gene variant. Both PET (positron emission tomography) and fMRI (functional magnetic resonance imaging) scans showed the same atypical activation. Such gene-hormone interactions may confer risk for mental illnesses, say the researchers.
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Study in mice suggests that overexpression of estrogen receptor 1 gene can impact post-menopausal breast cancer risk and prevention strategies. (2022) www.sciencedaily.com
From the article:
In a study using a first-of-its kind mouse model of aging that mimics breast cancer development in estrogen receptor-positive post-menopausal women, investigators at Georgetown Lombardi Comprehensive Cancer Center and colleagues have determined that over-expression, or switching on of the Esr1 gene, could lead to elevated risk of developing estrogen receptor-positive breast cancer in older women.
In a second study from the same research lab, investigators found that in the specially bred mice given anti-hormonal drugs (e.g., tamoxifen and letrozole) similar to those currently used by women to lower their breast cancer risk, the elevated risk of developing breast cancer due to over-expression of Esr1 could be lowered or reversed.
[…]
“If validated in human studies, detection of over-expression of Esr1-related genes could be a new signature to add to current prognostic tools that would help post-menopausal women at risk for estrogen receptor-positive breast cancer decide what their best risk reduction strategy might be.”
[…]
The investigators were guided in their study by the use of the PAM50 (Prediction Analysis of Microarray 50) prognostic tool. The tool reads a sample of the tumor and determines expression levels for a group of 50 genes. The scientists found that many genes related to proliferation of breast cancer cells in the PAM50 tool were significantly expressed only in Esr1 mice and this correlated with development of the same type of estrogen receptor-positive breast cancers that develop in humans, thereby giving them new evidence of which other genes might be implicated in inducing breast cancer in post-menopausal women. In current clinical practice, the results of the PAM50 test have helped predict the chance of metastasis for some ER-positive, HER2-negative breast cancers.
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Low estrogen levels may make women more susceptible to the development of post-traumatic stress disorder (PTSD). (2017) www.sciencedaily.com
From the article:
The scientists examined blood samples from 278 women from the Grady Trauma Project, a study of low-income Atlanta residents with high levels of exposure to violence and abuse. They analyzed maps of DNA methylation, a modification of DNA that is usually a sign of genes that are turned off.
[…]
“We knew that estrogen affects the activity of many genes throughout the genome,” […] “But if you look at the estrogen-modulated sites that are also associated with PTSD, just one pops out.”
That site is located in a gene called HDAC4, known to be critical for learning and memory in mice. Genetic variation in HDAC4 among the women was linked to a lower level of HDAC4 gene activity and differences in their ability to respond to and recover from fear, and also differences in “resting state” brain imaging. Women with the same variation also showed stronger connections in activation between the amygdala and the cingulate cortex, two regions of the brain involved in fear learning.
On top of that, experiments with female mice showed that the HDAC4 gene was activated in the amygdala while the mice were undergoing fear learning, but only when estrogen levels in the mice were low.
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Genetic differences drive the preference for sweet foods. www.sciencedaily.com
Whether a person prefers sweets over savory foods is related to their genetic makeup, a 2017 study found. These genetic differences may also drive alcohol consumption and tobacco use, the research showed.
Researchers analyzed the genetic makeup of more than 6,500 people to determine if they carried a particular gene variant of FGF21 – a hormone produced in the liver – called rs838133. Then they asked the participants about their sweet preferences, alcohol consumption, and tobacco use.
They found that participants who had the rs838133 variant were nearly 20 percent more likely to eat more sweet-tasting foods compared to the other participants. Those who had the rs838133 variant were also more likely to consume alcohol or smoke tobacco.
Next, the researchers asked 86 lean, healthy people about their sweet preferences and then, after a 12-hour fast, measured their FGF21 levels. They found that FGF21 levels in participants who had a low preference for sweets were 51 percent higher compared to those who had a high preference for sweets.
These findings suggest that FGF21 influences eating behaviors, curbing the appetite for sweets in some people. Other research suggests that FGF21 also moderates alcohol consumption, but it does it via different pathways. Taken together, these findings suggest that FGF21 release serves as a means to protect the liver from damage. Learn how exercise promotes the release of FGF21, thereby reducing cravings for alcohol.
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Quality of life in older hypogonadal men may be positively influenced by testosterone substitution. (2020) onlinelibrary.wiley.com
From the publication:
Testosterone plays a pivotal role in maintaining balance within the multi-dimensional psychological network of mood, behaviour, self-perception and perceived quality of life in men of any age. Apart from classical forms of hypogonadism, low testosterone concentrations can also be seen in older men, described as an age- and comorbidity-driven functional hypogonadism and might relate to depressive symptoms exhibiting a wide array of clinical pictures ranging from dysthymia and fatigue over inertia, listlessness to hopelessness and suicidal thoughts. Also, various traits of anxiety, from unfocussed fear to phobic anxiousness and open panic syndromes, are influenced by testosterone. Correspondingly, anxiolysis is likely to be modulated by testosterone via stress resilience, threat vigilance and reward processing. The steroid modulates pro-active and re-active dimensions of aggression, which has to be seen within the context of gaining or maintaining status. This may also include other strategies impacting the social position: heroic or parochial altruism and non-aggressive paths of assertiveness, such as posture and social vigilance. Independent rather than relationship-associated self-construal and self-esteem influence risk-taking traits under the modulation of testosterone. In addition, the genetic setting of the androgen receptor modulates the role of testosterone in aspects regarding mood and personality. Dimensions of sexuality are rather important in this context, but are not target of this article and covered in another part of this special edition. Overall, the quality of life in older hypogonadal men can be positively influenced by testosterone substitution, as has been demonstrated in large placebo-controlled trials.
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Research shows a 23% overlap between the genes that control testosterone and those that regulate body fat composition in men (2008) www.sciencedaily.com
From the article:
A strong correlation was found between sex hormones and body fat, which was predominantly due to shared genes. Specifically, testosterone and SHBG both showed a 23% genetic correlation with body fat, and SHBG [sex hormone-binding globulin] showed a 29% link with whole body fat. There was no link in terms of environmental factors between sex hormones and body composition.
When measured individually, testosterone had the highest heritability estimate of the sex hormones at 0.65 (heritability estimates are measured on a scale between 0 and 1, with 1 equalling 100% genetic influence). SHBG, weight and body fat also had high heritability estimates of 0.73, 0.83 and 0.65, respectively. Such high heritability values are similar to those previously published, and indicate that circulating testosterone levels are approximately 60% influenced by genes.
Previous studies have shown a well-established relationship between testosterone and body fat composition. For example, men with low testosterone levels are characterised by a high body fat percentage.
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In a mendelian randomization study, genetically predicted levels of interleukin 6 (IL-6) were associated with neuropsychiatric disorders. www.sciencedaily.com
IL-6 may drive inflammation in neuropsychiatric disorders.
Neuropsychiatric disorders are the leading cause of disability among people living in the United States, accounting for nearly 20 percent of all years of life lost to disability and premature death. Evidence suggests that brain inflammation is a key player in neuropsychiatric disorders, the effects of which may be bidirectional. A recent study identified potential links between inflammation and structural alterations in regions of the brain implicated in neuropsychiatric disorders.
The brains of people with neuropsychiatric disorders exhibit a range of abnormal structural alterations, but researchers don’t fully understand what drives these abnormalities. One possible player is interleukin-6 (IL-6), a cytokine that can cross the blood-brain barrier, increasing the barrier’s permeability and promoting brain inflammation. In turn, this inflammation can impair synaptic pruning, a natural process that occurs in the brain between early childhood and adulthood and eliminates extra synapses. Inappropriate synaptic pruning is associated with some neuropsychiatric disorders, including schizophrenia and autism.
The investigators searched for evidence of potential causality in the association between inflammatory cytokines and altered brain structure using Mendelian randomization, a research method that provides evidence of links between modifiable risk factors and disease based on genetic variants within a population. Using data from more than 20,000 adults enrolled in the UK Biobank study, the researchers looked for associations between genetic variants that influence levels of interleukin-6 (IL-6, a pro-inflammatory cytokine), as well as other inflammatory factors. and changes in gray matter volume in specific areas of the brain. They also examined postmortem brain tissue to assess gene expression in the brain areas of interest.
They found that genes that influence the production of pro-inflammatory molecules, especially IL-6, are strongly linked with brain structure in the temporal and frontal regions of the brain, areas of the brain commonly implicated in neuropsychiatric disorders. The postmortem analyses revealed that the overproduction of these pro-inflammatory genes is associated with disorders such as epilepsy, cognitive disorder, schizophrenia, psychotic disorder, and autism spectrum disorder.
These findings suggest that pro-inflammatory pathways, especially those associated with IL-6, are essential for normal brain structural development and IL-6 elevation may drive structural alterations implicated in neuropsychiatric disorders. Evidence suggests that heat stress reduces symptoms associated with depression, a type of neuropsychiatric disorder. Learn about a clinical trial that is investigating the benefits of heat stress in this episode featuring Dr. Ashley Mason.
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Age, gender and body size are better predictors of aortic aneurysm than atherosclerosis and hypertension. (2003) www.eurekalert.org
From the article:
“Atherosclerotic plaques and the risk factors that cause them, including hypertension, classically have been considered important potential causes of the expansion of the aorta,” says Bijoy Khandheria, M.D., a Mayo Clinic cardiologist and study author. “Intuitively, it makes sense that high blood pressure would stretch the vessel walls and make them more likely to become enlarged. This study shows that while these risk factors are highly important in a host of diseases and conditions, they are bit players when it comes to causing the dilatation of the aorta that can lead to aneurysm.”
[…]
The study found that age, gender and body size together account for one-third or more of the cases of aortic dilatation, while atherosclerosis and related risk factors only explained 3 percent.
“There has been a tendency recently to refer to aneurysms as ‘athersclerotic aneurysms,’” explains Dr. Khandheria. “But the fact that plaques – even complex or severe ones – are very common, while aneurysms are rare, supports the conclusion that atherosclerosis and its risk factors are not likely to blame for aneurysms in the major blood vessels of the chest. Other factors and processes, including genetic diseases similar to Marfan syndrome, seem to be more important.
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Data from nearly 80,000 twin pairs suggest that brain aneurysm ruptures are more commonly caused by environmental factors than by genes. (2010) www.sciencedaily.com
From the article:
During the past few decades, the genetic makeup has been regarded as playing a significant role in the development of SAH [subarachnoid haemorrhage]. Contrary to this belief, however, a twin study recently published in the journal Stroke showed that environmental factors account for most of the susceptibility to develop SAH Conducted in Finland, Sweden and Denmark, the study is the largest population level twin study in the world.
This means that instead of screening the close family members of SAH patients, the focus of preventive treatment may now be increasingly shifted to the efficient management of hypertension and smoking cessation intervention. This is what we do with other cardiovascular diseases as well."
The Nordic study combined data on almost 80,000 pairs of twins over several decades. All in all, the follow-up time of all of the twin pairs corresponds to a staggering 6 million person-years.
The researchers nevertheless emphasize that there are rare cases of families among whose members SAH is significantly more common than in the overall population. In these cases genetic factors are the principal cause underlying the development of the disease.
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Carriers of a gene variant that increases the chance of brain aneurysm by 37-48%, fivefold their risk if they smoke. (2010) www.sciencedaily.com
From the article:
Researchers have confirmed three gene changes that raise the risk that a blood vessel in the brain will weaken and balloon out (aneurysm), creating a life-threatening chance of rupture. Smoking, the biggest risk factor for brain aneurysm, is five times more dangerous in people with these gene variations. However, a second study on the same population notes that most people with aneurysm die of cancer or heart problems.
[…]
In one study (Broderick, abstract 156), researchers found that the chance of an intracranial aneurysm increased between 37 percent and 48 percent for people who carried one copy of an identified risky gene variation. However, when the gene variant was combined with smoking the equivalent of one pack a day for 20 years, the risk increased more than five-fold. People with two copies of the gene variant were at even higher risk.
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Insomnia, hypertension and smoking, but not high triglyceride levels, are considered possible risk factors for brain aneurysm rupture. www.sciencedaily.com
From the article:
Data from several genome-wide association studies were used to gauge genetic associations to lifestyle and cardiometabolic risk factors. […] According to the analysis:
-A genetic predisposition for insomnia was associated with a 24% increased risk for intracranial aneurysm and aneurysmal subarachnoid hemorrhage.
-The risk for intracranial aneurysm was about three times higher for smokers vs. non-smokers.
-The risk for intracranial aneurysm was almost three times higher for each 10 mm Hg increase in diastolic blood pressure (the bottom number in a blood pressure reading).
-High triglyceride levels and high BMI did not demonstrate an increased risk for intracranial aneurysm and aneurysmal subarachnoid hemorrhage.
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APOE4 carriers had a 4.92 higher odds of committing suicide in a high air pollution environment (mexico city) www.sciencedaily.com
Air pollution exposure promotes Alzheimer’s disease-related hallmarks in the brains of children.
Components present in air pollution – a mixture of chemicals, gases, and particulate matter – can cross biological barriers, including the blood-brain barrier. Evidence suggests that children exposed to air pollution exhibit altered brain structure and metabolic function and demonstrate impaired cognitive performance. A 2018 study identified pathological hallmarks associated with Alzheimer’s disease in the brains of children and young adults living in Mexico City, an area known for its high levels of air pollution.
The primary pathological hallmarks associated with Alzheimer’s disease are amyloid-beta plaques and tau neurofibrillary tangles. Amyloid-beta is a toxic 42-amino acid peptide that clumps together, forming plaques in the brain. Tau is a protein that, when modified via the chemical process of phosphorylation, can form aggregates called neurofibrillary tangles in the brain. Scientists classify the severity of neurofibrillary tangle formation according to the Braak staging system, which ranks severity on a scale of I to VI, with VI being the most severe.
The investigators examined autopsy-derived brain tissues from 203 subjects living in Mexico City, ranging in age from 11 months to 40 years, to identify the presence of amyloid-beta plaques and tau neurofibrillary tangles. They calculated the subjects' cumulative burden of particulate matter exposure based on their place of residence and noted the subjects' cause of death. They also conducted genotyping to determine whether the subjects were carriers of APOE4, a genetic variant that increases a person’s risk of developing Alzheimer’s disease.
They found that 99.5 percent of the subjects' brains exhibited abnormally high levels of amyloid-beta and hyperphosphorylated tau, even as early as 11 months of age. Approximately one-fourth of subjects between the ages of 30 and 40 years exhibited stage III or IV neurofibrillary tangles. Subjects who carried the APOE4 variant were at least 23 times more likely to exhibit stage IV tangles. Interestingly, APOE4 carriers were nearly five times more likely to commit suicide than non-carriers.
These findings suggest that exposure to air pollution in early life increases a person’s risk for developing Alzheimer’s disease. People who carry the high-risk genetic variant APOE4 are at substantially greater risk and may, additionally, be vulnerable to greater suicide risk. Omega-3 fatty acids help maintain blood-brain barrier integrity and may reduce the risk of Alzheimer’s disease in APOE4 carriers. Learn more in this open-access peer-reviewed article by Dr. Rhonda Patrick.
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Menopause disrupts sleep, accelerating biological aging www.sciencedaily.com
Menopause accelerates epigenetic aging.
Menopause, which typically occurs around the age of 52 years, is the cessation of a female’s menstrual cycle and signifies the loss of reproductive capacity. Evidence suggests that early menopause increases the risk for age-related disease and premature death. Findings from a 2016 study suggest that menopause accelerates epigenetic aging.
Epigenetics is a biological mechanism that regulates gene expression (how and when certain genes are turned on or off). Diet, lifestyle, and environmental exposures can drive epigenetic changes throughout a person’s lifespan to influence health and disease. Epigenetic age is based on a person’s DNA methylation profile and strongly correlates with their chronological age. However, some exceptions exist. For example, the epigenetic ages of semi-supercentenarians (people who live to be 105 to 109 years old) are markedly younger than their chronological ages.
The investigators analyzed the DNA methylation profiles of more than 3,100 women enrolled in four large observational studies (Women’s Health Initiative; InCHIANTI; Parkinson’s Disease, Environment, and Genes; and the National Survey of Health and Development) to identify links between epigenetic age and menopause. Their analysis was based on assessment of the biological age of cells taken from the women’s blood, saliva, and inner cheek. Because the age at which a female experiences menopause is heritable, they conducted a Mendelian randomization analysis to identify genetic links between age at menopause and epigenetic aging.
They found that menopause markedly accelerated epigenetic aging. Females who experienced earlier natural menopause were more likely to have “older” blood than those who experienced later menopause, but females who had surgical menopause (a surgical procedure in which the ovaries are removed) had older blood and saliva than those who experienced natural menopause. Cells taken from the inner cheek of females who took menopausal hormone therapies were younger than those who did not take hormones. They also found that a particular gene variant that influences the age at which a female experiences menopause also influences age acceleration.
These findings suggest that menopause accelerates epigenetic aging in females. The investigators conceded that their findings do not establish a cause-and-effect relationship, however. In a related study, researchers found that menopause-related sleep disorders, such as insomnia or poor sleep quality, contribute to the accelerated aging associated with menopause. Learn more about accelerated epigenetic aging in this episode featuring Dr. Steve Horvath.
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Pharmacological activation of PPAR delta boosts endurance by 70% in mice and other benefits: resistance to weight gain, better insulin responsiveness www.sciencedaily.com
From the article:
Developing endurance means being able to sustain an aerobic activity for longer periods of time. As people become more fit, their muscles shift from burning carbohydrates (glucose) to burning fat. So researchers assumed that endurance is a function of the body’s increasing ability to burn fat, though details of the process have been murky. Previous work by the Evans lab into a gene called PPAR delta (PPARD) offered intriguing clues: mice genetically engineered to have permanently activated PPARD became long-distance runners who were resistant to weight gain and highly responsive to insulin – all qualities associated with physical fitness. The team found that a chemical compound called GW1516 (GW) similarly activated PPARD, replicating the weight control and insulin responsiveness in normal mice that had been seen in the engineered ones.
[…]
Mice in the control group could run about 160 minutes before exhaustion. Mice on the drug, however, could run about 270 minutes – about 70 percent longer. For both groups, exhaustion set in when blood sugar (glucose) dropped to around 70 mg/dl, suggesting that low glucose levels (hypoglycemia) are responsible for fatigue.
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A woman’s body weight before and during pregnancy can have profound health effects on both mother and child. Women with obesity are at greater risk for developing pregnancy complications that can impair infant neurodevelopment, such as gestational diabetes, preeclampsia, preterm birth, and birth trauma. Findings from a new study suggest that maternal obesity contributes to attention deficit hyperactivity disorder (ADHD) and obesity in offspring.
ADHD is a neuro-behavioral condition characterized by inattention and/or hyperactive or impulsive behavior that interferes with functioning, learning, or development. Obesity is characterized as having excessive body fat – typically defined as having greater than 25 percent body fat for males and greater than 33 percent body fat for females.
The study included nearly 3,000 Finnish women and their offspring (~9,400 children). The authors of the study collected information about the children’s behavior and attention span from mothers and teachers. They gathered anthropometric data to determine the mothers' and children’s body mass index (BMI), a proxy for body fatness. They used Mendelian randomization and polygenic risk scores to assess risk for ADHD and/or obesity. Mendelian randomization is a research method that provides evidence of links between modifiable risk factors and disease based on genetic variants within a population. A polygenic risk score estimates a person’s genetic propensity for developing a trait or disease.
They found that children whose mothers had a high BMI were more likely to develop ADHD, independent of genetic makeup. The Mendelian randomization analysis identified a bidirectional link between developing ADHD and obesity-related traits, suggesting that certain genetic variations may predispose children to both ADHD and obesity concurrently. The polygenic risk score revealed evidence for genetic overlap between having ADHD and greater BMI.
These finding suggest that both genetic and prenatal environmental factors influence the likelihood that a woman’s child will develop ADHD and obesity. They also underscore the importance of maintaining a healthy maternal body weight before and during pregnancy.
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BDNF genetic variant Val66met found in ~30% of the population is associated with up to 20% worse performance on driving test www.sciencedaily.com
From the article:
People with a particular gene variant performed more than 20 percent worse on a driving test than people without it – and a follow-up test a few days later yielded similar results. About 30 percent of Americans have the variant.
Often there are benefits and trade-offs when it comes to genetics:
The gene variant isn’t always bad, though. Studies have found that people with it maintain their usual mental sharpness longer than those without it when neurodegenerative diseases such as Parkinson’s, Huntington’s and multiple sclerosis are present.
“It’s as if nature is trying to determine the best approach,” Cramer said. “If you want to learn a new skill or have had a stroke and need to regenerate brain cells, there’s evidence that having the variant is not good. But if you’ve got a disease that affects cognitive function, there’s evidence it can act in your favor. The variant brings a different balance between flexibility and stability.”
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Carriers of a common BDNF genetic variant demonstrate more rapid decline from Alzheimer's disease. www.sciencedaily.com
BDNF plays critical roles in many aspects of cognitive function, including learning and memory formation. A single-nucleotide polymorphism (SNP) in the gene that encodes BDNF causes a substitution of the amino acid valine (Val) by methionine (Met) in a specific region of the DNA where the gene is located. Evidence suggests that carrying the Met allele (Met/Met or Val/Met genotype) is associated with lower BDNF expression.. A 2017 study found that amyloid-beta burden impaired BDNF-related learning and memory.
Amyloid-beta is a toxic 42-amino acid peptide that aggregates and forms plaques in the brain with age. Amyloid-beta is associated with Alzheimer’s disease, a progressive neurodegenerative disease that can occur in middle or old age and is the most common cause of dementia.
The study involved more than 1,000 adults (approximately 55 years at the beginning of the study) who were enrolled in a larger study of Alzheimer’s disease. Nearly 65 percent of the participants were at high risk for developing Alzheimer’s disease, having at least one parent diagnosed with the condition. Each of the participants underwent cognitive assessment and BDNF genotyping five times over a period of four to 11 years. In addition, a small cohort of participants underwent imaging studies to assess amyloid-beta burden.
The genotyping revealed that approximately one-third of the participants were carriers of the Met-66 allele. Compared to Val/Val carriers, Met-66 carriers showed steeper declines in cognitive function. In addition, Met-66 carriers with greater amyloid-beta burden showed an even greater cognitive decline, likely due to lower BDNF expression. These findings suggest that a SNP in the gene for BDNF influences cognitive health and could serve as a therapeutic target against Alzheimer’s disease.
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BDNF genetic variant predicts success in alcohol dependence treatment. www.sciencedaily.com
Alcohol dependence is a complex disorder that increases a person’s risk of death from all causes. Findings from a 2009 study suggest that variations in certain genes can impact the likelihood of relapsing following treatment.
BDNF is involved in neuronal growth and survival, as well as influencing neurotransmitters – chemical signals from the nervous system. Low BDNF levels have been linked to the development of depression, anxiety, and alcohol dependence.
Previous research has demonstrated that alcohol dependence has a genetic component. The current study investigated whether common variations in certain genes would have an effect on post-treatment relapse.
The prospective study involved 154 participants who met the criteria for alcohol dependence and were admitted to a treatment facility. The patients provided blood samples for genetic analysis and completed self-assessment questionnaires about depression, hopelessness, impulsivity, and the severity of their alcohol use. The authors followed up with participants for approximately one year to assess whether they had relapsed. Relapse was defined as any drinking during the observation period, with heavy drinking considered as more than four drinks per day for more than four consecutive days. During the follow-up period, 59 (48 percent) participants relapsed, with 48 returning to heavy drinking. The average time to relapse was 218 days.
The authors tested a genetic variant that resides in the BDNF gene, known as Val66Met. They observed that participants with the Val form of this gene were more likely to relapse compared to those with the Met version. Participants with two copies of the Val allele – one from each parent – had higher rates of relapse and shorter times to relapse when compared to carriers of at least one Met allele.
These findings suggest that BDNF influences a person’s ability to remain abstinent following treatment for alcohol dependence. With further evaluation, these findings may help clinicians to identify people at increased risk for post-treatment relapse and tailor their care plans.
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Chimerism is a condition in which a person’s body contains two different sets of DNA. It can occur in fraternal twins and as a consequence of bone marrow transplantation. A recent news article describes a unique case of chimerism that could have implications for forensic scientists.
Three months after a man received a bone marrow transplant to treat his acute myeloid leukemia, some tissue samples from his body contained two sets of DNA: his own, and that of the donor. Other tissues had only the recipient’s DNA. Remarkably, the changes in the man’s DNA persisted for several years, and now, some four years after the bone marrow transplant, the DNA in his semen is exclusively that of the donor.
This case could have serious implications for the field of forensic science, especially when investigating sex crimes. For example, if an individual developed chimerism following a bone marrow transplant and then went on to commit a crime, it could mislead forensic investigators.
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Air Pollution, health, and genetic risk www.nature.com
[Abstract] Uncovering the interaction between genomes and the environment is a principal challenge of modern genomics and preventive medicine. While theoretical models are well defined, little is known of the G × E interactions in humans. We used an integrative approach to comprehensively assess the interactions between 1.6 million data points, encompassing a range of environmental exposures, health, and gene expression levels, coupled with whole-genome genetic variation. From ∼1000 individuals of a founder population in Quebec, we reveal a substantial impact of the environment on the transcriptome and clinical endophenotypes, overpowering that of genetic ancestry. Air pollution impacts gene expression and pathways affecting cardio-metabolic and respiratory traits, when controlling for genetic ancestry. Finally, we capture four expression quantitative trait loci that interact with the environment (air pollution). Our findings demonstrate how the local environment directly affects disease risk phenotypes and that genetic variation, including less common variants, can modulate individual’s response to environmental challenges.
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New here, Question about NRF2 en.wikipedia.org
Hi guys, shouting out from the great lake!! I’ll make this quick. So, lately I have been doing a lot of research. I recently watched/took notes on Dr.Rhonda Patrick’s Broccoli sprout video. In it she mentioned a lot of cool things about the veggie along with other veggies within that realm. During the video, she mentioned NFR2. I paused the video and looked it up before resuming so I could get a better handle on what she was mentioning. While digging into NFR2, I found something worth questioning.
In the WIKI article I have linked with this post, it states: Potential adverse effects of NRF2 activation “Genetic activation of NRF2 may promote the development of de novo cancerous tumors[32][33] as well as the development of atherosclerosis by raising plasma cholesterol levels and cholesterol content in the liver.[34] It has been suggested that the latter effect may overshadow the potential benefits of antioxidant induction afforded by NRF2 activation.[34][35]”
So my question is: If these cruciferous veggies increase/promote NRF2. Is it bad to eat Cruciferious veggies? Or too many? Wouldn’t that mean you would want to stay away from them? I know these questions may be silly but I’m just confused. I’m sure its fine to eat them, just curious. Anyone have any answers? PS I would recommend anybody to watch Dr. R.P. video on broccoli sprouts.