Aging & inflammation

Aging well Hunza man Hunza Valley

Aging well Okinawan woman Beach in Okinawa Coronary heart disease: 18/100,000 versus 100/100,000 in the USA

Prevailing theory of the cause of age related chronic illness Cumulative damage from oxidative stress and chronic inflammation leads to illness What is damaged? Carbohydrates, proteins, lipids, cell membranes, DNA Inflammation oxidative stress

Acute & chronic inflammation Acute inflammation occurs when, for example, we fight infections or heal wounds When visible, there are classic signs and symptoms: swelling, redness, heat and pain Chronic inflammation is an ongoing low grade type of inflammation that is not noticeable externally but can be assessed by specific laboratory tests

Oxidative stress Oxidative stress damages molecules that have important functions in living systems Oxidative stress occurs as a part of normal metabolism and is balanced by the body’s anti-oxidant network Oxidative stress is also triggered when we are exposed to ultraviolet light, tobacco smoke, environmental toxins and ionizing radiation.

Oxidative stress can set off chain reactions Oxidative stress leads to the generation of reactive oxygen species (ROS) ROS are unstable molecules that can initiate destructive chain reactions in the body- damaging cells and their normal functions Some examples of reactive oxygen species are: free radicals and hydrogen peroxide

Oxidative stress and chronic inflammation are linked to: Aging Arthritis Cancer Cardiovascular disease Cataracts Diabetes Osteoporosis Asthma

Heart disease and inflammation High sensitivity C-reactive protein (hsCRP) is a marker of inflammation in the body Elevated hsCRP has been found to be a stronger predictor of heart disease than a high LDL (harmful) cholesterol

Our anti-oxidant defenses The body has a complex set of anti-oxidant defenses to protect itself from the damage from reactive oxygen species These include anti-oxidants produced by the body and anti-oxidants ingested in foods Anti-oxidant defenses also include special mechanisms to repair damaged DNA, unique enzymes and physical barriers

Antioxidant defenses Vitamins: retinol (vitamin A), niacin, riboflavin, vitamin B6, vitamin C, vitamin D, vitamin E and vitamin K Omega 3 PUFA’s: eicosapentanoic acid, docosahexanoic acid, alpha linolenic acid Amino acids/peptides/proteins: taurine, glutamine, L- arginine, histidine, glycine, thiols, n-acetyl cysteine, carnosine, lactoferrin, transferrin, etc Phytochemicals: polyphenols, glucosinolates, carotenoids, allicin, etc Minerals: zinc, selenium, copper (+/-), iron (+/-) Enzymes: SOD (superoxide dismutase), CAT (catalase), GPX (glutathione peroxidase), glutathione S-transferase, thioredoxin, Co-enzyme Q10

Controlling excess inflammation Inflammation is influenced by the balance between series 1, 2 and 3 ‘eicosanoids’ Eicosanoids are locally produced compounds derived from polyunsaturated fatty acids (PUFA’s) Eicosanoids include prostaglandins, thromboxanes, leukotrienes These compounds govern many diverse physiological processes in the body: cell growth and differentiation, blood clotting and key aspects of immune function

Key points It is important to have a balance between the different kinds of eicosanoids The kinds of eicosanoids we produce is directly influenced by the types of fatty acids in the diet Series 1 and 3 eicosanoids have anti- inflammatory effects Series 2 eicosanoids promote inflammation

Sources of omega 3 fatty acids Alpha linolenic acid: flax, walnuts, canola oil, soy, hemp, chia seeds EPA/DHA: fatty fish such as wild salmon, black cod, herring, halibut, sardines

Linoleic acid (LA) Gamma-linolenic acid (GLA) Arachidonic acid (AA) Alpha-linolenic acid (LNA) Eicosapentanoic acid (EPA) Docosahexanoic acid (DHA) Omega 6 pathway Omega 3 pathway Omega 6 pathway Omega 3 pathway Delta-6 desaturase Elongase PG1 PG2 PG3 Safflower, sunflower, corn, peanut oils Flax, walnuts, hemp, canola Salmon, halibut sardines, herring Evening primrose oil Meat, butter Salmon, halibut, sardines, herring

Thus… Over consumption of omega 6 fats can lead to increased inflammation Consumption of omega 3 fats has anti- inflammatory effects North American diets tend to have excessive amounts of omega 6 fatty acids and high ratio of n-6 to n-3 fatty acids North American dietary patterns therefore tend to promote chronic inflammation

Causes of the imbalance between omega 6 and omega 3 fatty acids Widespread use of vegetable oils, such as safflower, sunflower, corn, peanut, etc High intake of arachidonic acid from animal foods Grain fed (high intake of omega 6’s) as opposed to pasture fed (high intake omega 3’s from grasses) animals

Grain fed, grass fed and wild game Data from J. Animal Sci 80(5):

Diet/lifestyle choices that can increase oxidative stress and inflammation Cigarette smoking Overeating High glycemic index carbohydrates Omega 6 fats/trans fats/saturated fats Lack of antioxidant nutrients in the diet Chronic stress

Stress hormones: the adrenal glands The major stress hormones are released from the adrenal glands:  adrenaline, noradrenaline  cortisol

Sympathetic Nervous System (SNS)  Heart rate  RR  Blood pressure  Blood glucose  LDL cholesterol Senses are sharpened Blood flow is directed to exercising muscles

Stress is *catabolic Our physical reaction to stress is analogous to burning the dining room furniture to stay warm during a power failure. *Catabolism: the breakdown of complex materials in an organism

SNS: What’s turned off? Getting rid of unnecessary energy expenditure Digestive tract: enzymes, blood flow, peristalsis Tissue growth and repair Immune function Sex drive Pain sensation Testosterone and estrogen production

Chronic stress and brain function During stress, the brain’s ‘executive functions’ are disengaged (moral reasoning, judgment, planning) More primitive, reflex areas of the brain remain engaged (sleep/wake cycles, spatial memory) High cortisol levels interfere with learning and memory and may lead to permanent damage to neurons in the brain

Chronic stress & aging Telomeres protect the ends of chromosomes during cell division. Accelerated telomere shortening is associated with aging, CVD, HIV, etc Telomerase is a cellular enzyme that promotes telomere repair Chronic stress and elevated cortisol levels have been found to reduce the activity of telomerase

Chronic stress and immune function Stress results in a significant decline in natural killer (NK) cell cytotoxic activity. NK cells play a key role in immune system surveillance against viral-infected cells and cancer cells. Stress also reduces the production of secretory IgA- an important part of immune response in the gastrointestinal system, urinary tract and lungs

Results of chronic stress Stress has been found to:  slow wound healing  diminish the strength of immune responses to vaccines  enhance susceptibility to infectious agents  reactivate latent viruses

Stress, heart disease & inflammation Stress can result in inflammation of the arterial walls and an increased tendency of the blood to clot  leading to atherosclerosis and an increased risk of heart attack and stroke Stress can lead to a more atherosclerotic lipid profile: increased LDL cholesterol Stress can raise blood pressure and blood glucose

Chronic stress and resiliency Relatively stress free individuals are resilient and can more readily rebound from an acutely stressful event Chronically stressed individuals are less able to rebound from an acute stresses. They may suffer a greater degree of distress, and exhibit higher peak adrenaline levels and greater reductions in NK cell activity

Chronic stress and visceral fat Higher cortisol levels are associated with an increase in visceral fat Visceral fat is linked to increased risk of coronary artery disease, stroke, hypertension and diabetes

Chronic stress: appetite and food choices About 70% of people increase their caloric intake when stressed. Most people choose calorie dense foods such as highly processed carbohydrates (pastries, chips, bread) and or foods rich in fat such as ice cream and chocolate High cortisol levels, high insulin levels, and consuming calorie dense foods all tend to promote increased visceral fat distribution

What to do? We can support our body’s anti- oxidant system and reduce chronic inflammation and stress by choosing certain foods and lifestyle behaviors

Foods that support the anti-oxidant system Vitamin E: nuts, avocados, olive oil Vitamin C: oranges, peppers, papayas Beta carotene: carrots, leafy greens, squash, sweet potatoes Selenium: brazil nuts, seafood, oatmeal Copper, zinc & manganese: nuts, meat, beans, berries, dark leafy greens, whole grains Riboflavin: liver, milk, eggs, spinach, brown rice Sulfur containing amino acids: seafood, meat, cheese, peanuts, sunflower seeds, lentils, pumpkin seeds, sesame seeds

The antioxidant network Vitamin C is the body’s major water soluble anti-oxidant Vitamin E is the body’s major fat soluble anti-oxidant Vitamin C can regenerate vitamin E and glutathione Glutathione can regenerate vitamin C & E Coenzyme Q10 regenerates vitamin E Lipoic acid can regenerate vitamin C and E and raises glutathione levels

‘Anti-inflammatory diet’ Abundant fruits and vegetables Healthy fats: olive oil, nuts, fatty cold water fish, fish oil Low glycemic index/load carbohydrates Green tea, turmeric, ginger

A rainbow of colors 8-10 servings per day of a wide variety of colors and kinds of fruits and vegetables

Servings of Fruits and vegetables One medium sized fruit or vegetable 1 cup of salad ½ cup of cooked vegetables One 4oz glass of fruit juice

How to get enough fruits and vegetables Have at least 2 servings with breakfast & lunch  Mixed berries or a glass of fruit juice and an apple with breakfast  A salad or raw vegies with dip with lunch Have at least 3 servings with supper  Baked squash, green beans and beets  Swiss chard, carrots and broccoli Have at least 1 snack (preferably 2) per day  A pear, some plums, banana, carrot sticks, etc

Fruits and vegetables reduce oxidative stress and inflammation  C-reactive protein (CRP)  Interleukin-6 (IL-6)  Tumor necrosis factor-   F- 

Healthy fats Extra virgin olive oil: a good source of monounsaturated fats and high in anti- inflammatory polyphenols Omega 3 essential fatty acids from fatty fish (e.g. salmon), canola oil, walnuts, hemp, flax, dark leafy greens

Avoid/reduce unhealthy fats Omega 6 vegetable oils- safflower, sunflower, corn, peanut Trans fats-margarine, crackers, peanut butter, deep fried food Saturated fats-meat and dairy products

Low glycemic index carbohydrates Whole grain breads, cooked whole grains (quinoa, bulgur, barley), al dente pasta, large flake oats, Basmati rice, Uncle Ben’s converted rice, dairy products, beans, nuts, fruits, vegetables

Spices and teas Green tea (best if steeped for at least 3 minutes) Turmeric, ginger Rosemary, oregano

Okinawan diet The Okinawan Centenarian Study (OCS) found that elder Okinawans ate (per day):  7 servings of vegetables  7 servings of whole grains  2 servings of soy foods  fish 2-3 times per week.  Consumption of meat and dairy products was very low. They ate very little sugar or added fats.  They eat primarily whole unrefined grains and do not eat margarines or hydrogenated fats.

Okinawan diet Overall, when compared to a western diet, Okinawans ate:  more vegetables, grains, soy foods, and fish  far less meat, poultry, eggs, and dairy products and less fruit

‘Anti-inflammatory diet & lifestyle’ Abundant fruits and vegetables Healthy fats: olive oil, nuts, fatty cold water fish, fish oil Low glycemic index/load carbohydrates Green tea, turmeric, ginger Reduce stress Get regular exercise