Insane Medicine – mitochondria and aging – NAD+ and Sirtuins as part of the missing link

Insane Medicine -Aging and mitochondria
Insane Medicine -Aging and mitochondria – aging as a result of mitochondrial and nuclear gene miscommunication. Low levels of NAD in the cell cause HIF -1 to increase, which results in the nucleus and mitochondria to not communicate.
  • The mitochondrion is a cellular organelle that provides the cell with the energy needed to sustain life. It has it’s own genetic material that produces, in part with the nucleus, an oxidative-phosphorylation complex in the cell that produces all our energy. Basically, the mitochondria is a piece of machinery that acts like a battery for the cell.
  • As we age, it has been found that the genes in the mitochondrion mutate and function poorly. This may be the root cause of aging. NAD+ is a molecule used as an energy carrier that regulates the mitochondria, as it decreases in low oxygen states and results in a disruption of the oxidative phosphorylation complex. Increasing the NAD+ levels reverses this rocess.
  • In a functioning normal cell, the nucleus and the mitochondiron communicate with each other and manufacture, using their genes, the oxidative phosphorylation complex, which is the producer of the energy inside the mitochondria. It is the failure of the genes inside the mitochondria that result in the aging process.
  • A gene, called sirtuin 1 is involved in maintaining a clear line of communication between the nucleus and the mitochondrion. HIF-1 is a protein that the cell produces in cancer states and low oxygen states that interferes with this communication process, causing cell aging and death.
  • Aging muscles have been found to have decreased levels of mitochondrial genes.
  • Nuclear levels of NAD+ maintain the mitochondiral homeostasis, with decreased levels disrupting the oxidative-phosphorylation machinery in the cell and thus result in cell aging and death. Raising this NAD+ nuclear level in mice reverses this aging process. Molecules have been developed that can do this.
  • There is a separate system, the PGC-1α/β system, that also regulates energy metabolism in cells and acts as a transcriptional coactivator to regulate gene activity and function. It works separately from the above. PGC-1α regulates mitochondrial biogenesis and interaxcts with nuclear PPAR-gamma, which results in the interaction of numerous transcription proteins that affect cell function. This directly links the external stimuli of the world to the internal cell functioning of mitochondria. For example, PGC-1α may be involved in cholesterol regulation, obesity, and blood pressure.  PGC-1α may  integrate a number of internal cell signals with external signals. For example, endurance exercise increases PGC-1α levels and allows for lactate to be used more efficiently. SIRT-1 may bind and activate PGC-1α.. PGC-1α activates Akt levels in muscle, which is pro-survival in function. Massage therapy can increase PGC-1α, allowing formation of new mitochondria.
  • http://www.cell.com/abstract/S0092-8674%2813%2901521-3
Insane medicine - mitochondria
Mitochondria are the work horse of the cell,producing it’s energy, but also they may be the root cause of aging.
Insane Medicine - Mitochondria are the work horse of the cell,producing it's energy, but also they may be the root cause of aging.
Mitochondria are the work horse of the cell,producing it’s energy, but also they may be the root cause of aging.

http://hms.harvard.edu/news/genetics/new-reversible-cause-aging-12-19-13  <- anti-aging and mechanism regarding this

  • Possible interventions for the process of aging?  Nothing is yet on the market, but some agents may have helpful anti-aging effects: trans-resveratrol is one option.  Red wine, mulberries, grapes, and peanuts have resveratrol. A glass of wine has a milligram of the substance. A higher amount is needed to be effective. About 360 mg may be needed to have an anti-aging effect. It has been noted that in countries where red wine is imbibed, people are thinner and live longer. An option for resveratrol in needed doses can be obtained here:

http://www.longevinex.com/home.php

Calorie restriction has been a way to extend lifespan in animals such as rats. The process of calorie restriction causes the aging machinery to slow down.  Trans-resveratrol simulates calorie restriction without actually eating less. This may be a way to trick the body into a “fasting, yet anti-aging” state.

 

 

Insane Medicine – Chronic pain and it’s emotional component

  • Chronic pain affects both cognitive and emotional circuits in the brain as both mood and cognition are affected. Basically, an injury causes changes in the body’s chemistry and function which results in a change in the brain’s circuitry on how we perceive pain. Normal emotional processing is damaged.
  • Initially, acute pain is perceived in brain regions involved with pain reception, but as it transitions to chronic pain, it is perceived in centers of the brain that are involved with the mediation of emotions. Chronic pain involves abnormal stress responses, in which patients with chronic pain have higher cortisol stress hormone released to a painful stimulus. They also have smaller hippocampus areas of the brain that are involved in memory, learning, and emotions, This area of the brain begins to process pain signals poorly while areas of the brain that are involved in anticipatory anxiety and associative learning have over activity. There appears to be connectivity problems between brain areas involved in mood and cognitive function. This results not on ly in the sensation of pain, but also mood disorders such as anxiety and problems with decision-making.
  • Significant factors leading to chronic pain include non-restorative sleep, anxiety, memory impairment, and poor quality of life.
  • Things that help: Get regular exercise at least 30 minutes a day for 5 days a week. Ensure healthful sleep with good sleep hygiene. Be certain to sleep in a quiet, comfortable environment and avoid caffeine and strenuous activities before bedtime. Become more active in Lifesocialize more and get involved with hobby or helping others.
  • Other options for treatment include vagal-nerve stimulation to interfere with pain perception and transcranial magnetic stimulation, in which a magnet is used to alter nerve circuits in the brain that are involved with pain. Cognitive behavioral therapy, acupuncture, and meditation are also means of combating chronic pain.

Insane Medicine – Muscle mass predicts longevity in older adults!

A study in the American Journal of Medicine (June 2014) showed that people over the age of 55 who had the highest muscle mass lived longer than those with the least amount of muscle mass. BMI (Body mass index) is not correlated as well with mortality since a person with a high BMI can have a lot of fat OR muscle or both.

http://www.nhlbi.nih.gov/health/educational/lose_wt/BMI/bmicalc.htm   – Calculate your BMI with this link!

Insane Medicine – An active body results in a healthy brain!

  • You can expand your mind in a healthy way through exercise. Stair climbing, swimming, jogging, dancing, yoga, and weight-lifting can increase your mental powers by providing increased blood flow to the brain and thereby nutrients. This helps neurons grow and repair themselves in aging minds.
  • Exercise-related infusions of oxygen-rich blood helps the brain operate. As it consumes a quarter of the oxygen taken in by the body, any increased flow is helpful in brain functioning.
  • The increased flow of blood to the brain increases glucose flow as well and also increases growth factors such as nerve growth factor and insulin-like growth factor, and brain-derived neurotrophic factor to increase. These  allow the brain to increase it’s internal connectivity and plasticity – important for memory formation and retention.
  • Exercise increases new brain cell formation in the hippocampus, a site involved in memory formation. Lack of activity causes the brain to decline in many components,  showing up as decreased density in gray matter (involved in memory) and white matter (involved in connections in the brain). Over time, with inactivity, one loses cognitive performance.
  • The more you exercise, the stronger and more dense the connections are within the brain. Also, there is increased immune function in the brain. The active body allows an active mind to regenerate axons when damaged, maintaining a person’s cognition. thereby preserving memory. Also, physical activity elevates one’s mood.
  • Side effects of exercise: blood pressure control, loss of weight, and decreased cardiovascular disease.

Insane Medicine – coconut oil and its benefits?

coconut-oil
coconut-oil
  • Coconut oil is obtained from the white meaty interior of the coconut (Cocos nucifera). It is solid at room temperature and has a long shelf life.
  • Coconut oils is high in saturated fat, even more than butter has in it.
  • The fat in coconuts has been found to not be as harmful as once believed. Now it is replacing other oils in baking and frying, to which it supplies a nutty, sweet flavor.
  • The saturated fats in coconuts are neutral in their effect on blood cholesterol. The main fatty acid is Lauric acid which raises HDL levels and LDL, but less so. Populatioins that consume a lot of coconut and coconut oil have lower rates of cardiovascular disease and tend to be healthy (Polynesia, for example)
  • Coconut oil has medium-chain triglycerides (MCT) in it, whereas most dietary fat consumed is longer-chained. This type of fat has a different metabolism that burns more calories in it’s consumption. Each tablespoon has 120 calories in it.
  • People have recommended coconut oil as a weight reducing agent. There is not enough evidence for this.
  • Coconut oil has been recommended for Alzheimer’s disease treatment. It is thought the MCT in the oil causes the liver to produce ketones that the brain can then use in place of glucose. There is no evidence that this works.
  • Coconut water: is a thin liquid inside green coconuts taht is fat-free and low in calories. It does not have all the electrolytes you need in it for fluid replacement however.
  • Coconut milk: is made from the coconut meat and has high calorie content (445 calories a cup). It has 48 grams of fat per cup. It does not seem to adversely affect one’s cholesterol however.
  • Coconut sugar: Made from the nectar of the flowering buds of a coconut tree and has no health benefits. Taste: caramel flavor.
  • Coconut flour: Made from the meat of the coconut, adds a coconut flavor to baked goods. It has high fiber in it (10 gm per oz) and a fat content of 4 gm per ounce.
  • Coconut meat: is from the inside lining of the coconut, having 100 calories in an ounce with 9 gm of fat and 2.5 gm of fiber.
  • Overall, there in no proven health benefits to using coconut oil and  coconut products.

Insane Medicine – Eating and mood/memory

  • A diet high in uridine monophosphate (UMP), choline, and docosahexanoic acid (DHA – an omega-3 fatty acid) helps increase the brain’s ability to process information. These substances help the brain form more synapses, which are important in creating memories. These substances affect the transmission of messages in the brain which thereby improves cognition.
  • Choline is synthesized in the body and is found in nuts, meats, and eggs. DHA is found in flaxseed, eggs, and meat from grass-fed animals. Also trout, salmon, tuna, and sardines are high in DHA. UMP is created in your body but is also present in high amounts in beets.
  • Eating correctly affects your mood as well. For example, when you eat a heavy lunch, you tend to bee more relaxed and sleep. People who are hungry tend to move less and be more irritable, They will generally make poorer decisions as well. If you are moody, maybe you are eating incorrectly!
  • There is a link between magnesium intake and depression. The less magnesium in your diet, the greater the risk of depression. Magnesium is found in whole grains, nuts, and seeds.
  • Low intake of B12 and folate is also associated with depression. Folate is found in green leafy vegetables, legumes, and fortified cereals. B12 is found in meat.
  • Nutrients affect how neurotransmitters are made in the brain, and the composition of the meal affects which neurotransmitters are made and thus how you feel after eating.
  • Protein-rich meals have amino acids, including tyrosine, which is used to make dopamine, norepinephrine, and epinephrine. These neurotransmitters give you more alertness, energy,  and focusing-ability. Carbohydrate-laden meals supply glucose (as in processed food, white breads)  and trigger rapid insulin release in the body which causes tryptophan to be converted to serotonin in the brain. This results in calm feelings, relaxation , and pain relief. It has been shown that babies given sucrose pacifiers during medical procedures have much less pain, for example.
  • The problem with foods that have high amounts of  simple carbohydrates is that you get spikes and drops in your blood sugar. This can make you moody and shaky. Replace simple carbohydrates with complex ones found in whole grains, fruits, and vegetables.
  • Vitamin C (citrus fruits and dark vegetables) and the B vitamins are helpful in mood control. Monounsaturated fats (nuts, olive oil, canola oil), omega-3 fatty acids (fish), selenium (cereal grains and meat), and zinc (fish, soybeans, liver, spinach, and egg yolk) all have positive affects on mood states.
  • Alcohol and caffeine also have the ability to moderate mood. Caffeine causes increased alertness and energy, but it can cause jitteriness and anxiety in some. Moderate alcohol  intake (one to two drinks a day) promotes relaxation, but in excess, can produce depression.  Chocolate has a substance called phenylethylamine that elevates mood.

Insane Medicine – Resveratrol in wine has multiple benefits – drink in moderation only though!

Insane Medicine - Wine
Red wine can benefit the body and the brain when taken in moderation.
  • Resveratrol is an antioxidant that may benefit the brain as a neuroprotecting agent. It neutralizes the effects of cell-damaging free radicals caused by pollution, stress, metabolism, aging, and other sources.
  • Resveratrol may protect against cardiovascular diseases, diabetes, and neurodegeneration.  It alters inflammation by affecting a class of enzymes called sirtuins that play a role in the aging process.
  • Resveratrol helps eliminate cell-damaging free radicals and enhances the survival mechanisms of cells. It may have anti-cancer properties as well.
  • Women should consume one 4 oz glass of wine per day at most and men can consume up to two 4 oz glasses of wine. Resveratrol is absorbed best by sipping the wine, as it’s absorption is enhanced by contacting the mucus membranes of the mouth.
  • Resveratrol may reduce beta-amyloids in the brain, which are associated with Alzheimer’s disease. It also helps modulate cell communication in the brain as well, which is important for memory. Resveratrol may also protect against oxidative stress and damage from diabetes.

Insane Medicine – Protecting your brain – the blood brain barrier

  • The brain is protected by the blood-brain barrier (BBB) which is composed of densely packed cells in the blood vessels that prevent entry of most substances into the brain. It does allow oxygen and nutrients, along with hormones to enter from the blood supply, but it blocks most other agents and bacteria. The BBB also removes brain waste matter such as beta-amyloid proteins that cause Alzheimer’s disease.
  • Breakdown of the BBB can result in catastrophic brain injury or death. It has been found that a number of factors can increase such a failure of the BBB. The first is sleep deprivation. In such cases, the BBB is weakened,allowing passage of drugs and chemicals that generally cannot enter the brain and results in brain damage.
  • High blood pressure, traumatic brain injury, obesity, viral infections, and inflammation also weaken the BBB. Again, a failed BBB results in brain damage slowly over time, especially by the accumulation of beta- amyloid, which leads to Alzheimer’s disease.

Preventing BBB failure:

  • Eat a diet high in Thiamine (Vitamin B-1) : pork, whole grains, sunflower seeds, kale, beans, and peas have a lot of Vitamin B-1.
  • Exercise regularly
  • Prevent brain injury: wear a helmet
  • Reduce cholesterol levels. High levels disrupt the BBB.
  • Consume caffeinated drinks, which block disruptions in the BBB.
  • Get at least 6-8 hours of sleep.
  • Lose weight, avoid obesity.
  • Avoid chemicals – some of which are toxic, such as polychlorinated biphenyls and the drug ecstasy, all of which disrupt the BBB.

Insane Medicine – Other weight loss options using medications

  • Orlistat – inhibits pancreatic and gastric lipase, an enzyme involved in fat absorption, and when taken three times daily, results in 2.5-3.2 kg weight loss in a year. It is associated with increased flatulence and fecal urgency.
  • Bupropion ( Wellbutrin SR) is used for tobacco addiction (Zyban) but can cause people to lose weight by as much as 10% using a 400 mg a day dosing. Mixing Buproprion SR with naltrexone (an opioid receptor antagonist) works even better. Its side effects include headaches and nausea.
  • Topramate (Topamax) at doses up to 256 mg a day results in ~9.7% weight loss, but for some, the drug causes tingling, sleepiness, and decreased concentration ability.
  • Metformin, a drug for diabetes and impaired glucose metabolism also results in modest weight loss.
  • Human chorionic gonadotrophin (HCG) is sold on the internet for oral consumption. It is not absorbed by the gut.
  • Antidepressants, such as selective serotonin reuptake inhibitors (Paxil, zoloft, and prozac) also are partially effective initially in suppressing appetite and causing weight loss.
  • Sympathetic aminesDiethylpropion (Tenuate), methamphetamine (Desoxyn), Phendimetrazine (Bontril) are in the same class as phentermine (Adipex-P) and are FDA approved for short-term use for weight loss. The amount one loses is approximately 3 kg. They can increase your heart rate and blood pressure.
  • Other medications associated with weight loss include Liraglutide (Victoza), Pramlintide (Symlin), and Byetta (Exenatide), which are all used in diabetes and result in some degree of weight loss. The antiepileptic zonisamide can result in  a 6 kg weight loss as well over a 4 month period.

Insane Medicine – Belviq for weight loss

belviq
belviq
  • Belviq (Lorcaserin) is a serotonin 2C receptor activator that suppresses appetite.
  • It does not cause cardiac valve problems, pulmonary hypertension, or hallucinations that can occur with serotonin receptor activation.
  • The goal is greater than 5% body weight loss in the year.
  • This treatment resulted in improvement of diabetes, with the Hemoglobin A1c ( a measure of glucose control) dropping by up to 1 %.
  • Side effects are headache, nausea, and dizziness. The dosing is 10mg twice a day, with doses over 40 mg causing euphoria, hence the drug is a controlled drug!

 

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