Inflammation influence on aging process itself, not just age related disease
We know NAD+ levels go down dramatically as we age. Many recent and ongoing research studies are investigating protocols for boosting NAD+ levels in elderly individuals to combat both disease and infirmities related to aging. Supplementing with Nicotinamide Riboside and/or NMN are 2 that are attracting a great deal of attention, especially after Dr David Sinclair demonstrated that raising NAD+ levels in elderly mice could “turn back the clock” leaving them with muscular function of young mice.
- NAD+ is key for mitochondria to perform all functions within the body
- NAD+ levels go down as we age
- Lower NAD+ levels impair all functions in the body
- Inflammation lower NAD+ levels
What you can do about it:
- Weight Training
Diet and Nutrition
- Weight loss – especially visceral fat
- foods – dr axe, perricone, weill (trufood restaurants)
- Grape Seed Extract
- omega 3 oils
- Green Tea
What is Inflammation?
from watson at antiagingfirewalls.com
Inflammation is a necessary part of our bodies defensive response to injury and disease, as it strives to eliminate the cause of irritation and is an essential initial stage of healing injured tissues. We could not survive without it. Unfortunately, if the cause of the irritation or illness is not eliminated, inflammation can often get out of control. Such Chronic Inflammation is now recognized to be both a cause and effect of nearly ALL age related conditions such as cancer, arthritis, metabolic syndrome, heart disease, osteoporosis, Alzheimers, IBS, asthma, COPD, depression, fatigue and more (4, 5, 6).
Anything that can help fight chronic inflammation is of potential importance in preventing and even treating these diseases. For example, Curcumin a powerful anti-inflammatory that matches the effectiveness of many prescription drugs in treating some chronic conditions, but without the side effects (7, 10, 11, 12, 13, 14). You can read more about some of the amazing benefits of Curcumin here.
Chronic inflammation, sometimes referred to as constitutive inflammation, other times as inflammaging, can persist over an extended period of weeks to months and even years. It is often associated with the presence of macrophages and lymphocytes, fibrosis, vascular proliferation, and tissue destruction. Moreover, chronic inflammation plays critical roles in many disease processes including cancers, dementias, diabetes, pulmonary diseases, cardiovascular diseases, atherosclorsis, sarcopenia, and anaemia. Chronic inflammation occurs in the case of incurable autoimmune diseases such as arthritis, lupus, scleroderma, asthma and chronic obstructive pulmonary disease (COPD).
The biological mechanisms of chronic inflammation can be very complex, Nuclear factor- B (NF-κB) is activated by more than 200 different stimuli has for good reason been thought of as the master activator of inflammation. It is a central topic in this blog entry. For example, during inflammation immune system macrophage cells could be activated by Toll-like receptors (TLRs), through the recognition of a pathogen endotoxin such as lipopolysaccharide (LPS). This event initiates a signaling pathway that releases NF-κB into the cell nucleus, activating genes associated with the transcription of proteins related to the inflammatory process, such as iNOS, responsible for NO synthesis, COXs, which synthetize prostaglandins, and cytokines like IL-6. The generation of ROS is also triggered by the TLR signaling pathway.
Among the highly technical topics related to chronic inflammation and its consequences are Activating protein-1 (AP-1), AGEs, RAGE receptor, PAMPs, DAMPs, RNS, leukotrienes, LOX, prostaglandins, COX1, COX2, Resolvins, Protectins, Maresins, the NLRP3 inflammasome, lipoxins, Ca++ induced inflammation, pyroptosis, cellular senescence-induced inflammation, roles of inflammation in aging, potassium efflux out of a cell, mitochondrial ROS, translocation of NLRP3 to the mitochondria, cytosolic release of mitochondrial DNA, cardiolipin release, release of lysosomal cathepsin D into the cytosol, extracellular LPS “priming” of NLRP3, amyloid-beta “triggering” of NLRP3 via TLR4, ATP, and pore-forming toxins. We expect to touch on most of these in this blog series on inflammation.
Inflammation and aging
Since chronic inflammation plays central roles in numerous deleterious health processes and in aging, it is often referred to as “inflammaging” and is the subject of much ongoing research. From the 2014 publication Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases: “Human aging is characterized by a chronic, low-grade inflammation, and this phenomenon has been termed as “inflammaging.” Inflammaging is a highly significant risk factor for both morbidity and mortality in the elderly people, as most if not all age-related diseases share an inflammatory pathogenesis. Nevertheless, the precise etiology of inflammaging and its potential causal role in contributing to adverse health outcomes remain largely unknown. The identification of pathways that control age-related inflammation across multiple systems is therefore important in order to understand whether treatments that modulate inflammaging may be beneficial in old people.”
The 2016 publication Inflammaging and Anti-Inflammaging: The Role of Cytokines in Extreme Longevity points out the central linkages between inflammation and aging. “Longevity and aging are two sides of the same coin, as they both derive from the interaction between genetic and environmental factors. Aging is a complex, dynamic biological process characterized by continuous remodeling. One of the most recent theories on aging focuses on immune response, and takes into consideration the activation of subclinical, chronic low-grade inflammation which occurs with aging, named “inflammaging.” Long-lived people, especially centenarians, seem to cope with chronic subclinical inflammation through an anti-inflammatory response, called therefore “anti-inflammaging.” In the present review, we have focused our attention on the contrast between inflammaging and anti-inflammaging systems, by evaluating the role of cytokines and their impact on extreme longevity. Cytokines are the expression of a network involving genes, polymorphisms and environment, and are involved both in inflammation and anti-inflammation. We have described the role of IL-1, IL-2, IL-6, IL-12, IL-15, IL-18, IL-22, IL-23, TNF-α, IFN-γ as pro-inflammatory cytokines, of IL-1Ra, IL-4, IL-10, TGF-β1 as anti-inflammatory cytokines, and of lipoxin A4 and heat shock proteins as mediators of cytokines. We believe that if inflammaging is a key to understand aging, anti-inflammaging may be one of the secrets of longevity.” This is an opinion I (Vince) hold. In a later blog entry in this series, I will share some of the approaches to anti-inflammaging I have been personally and professionally pursing.
Chronic Inflammation accelerate aging and disease
Dr. Perricone’s years of research have shown that the inflammation-aging connection is the single greatest cause of aging and age-related diseases such as heart disease, diabetes, Alzheimer’s disease, arthritis, certain forms of cancer, diminished mental and physical energy, the loss of muscle mass and wrinkled, sagging skin.
This chronic inflammation goes on day after day, year in and year out, leading to disease states as well as the disease of aging. In fact, aging is a chronic, uniformly progressive, inflammatory disease that is always fatal.
Our food choices are critical when it comes to causing and controlling inflammation. This is good to know because it actually means we are in control of the situation!
This is the key to health, longevity, mental clarity, well-being and beautiful youthful skin. Foods that are pro-inflammatory, such as all forms of sugar, processed foods, pasta, breads, pastry, baked goods, and snack foods such as rice and corn cakes, chips, pretzels, etc., cause a highly destructive pro-inflammatory response in our bodies. If we choose sugary or starchy foods, we trigger this pro-inflammatory release of sugar into our bloodstream, which causes our body to store fat rather than burn it for energy.
The result? Acceleration of the aging process of all organ systems in our body, including the skin, causing an increased risk of degenerative disease and inflexible, wrinkled, sagging skin. In addition, by eating that muffin or couple of cookies, the resulting insulin response triggers our appetite—causing us to crave more and more of these types of carbohydrates, resulting in a vicious cycle of overeating.
That is the bad news! Now for the good news:
Fortunately we can control inflammation in our bodies. It starts with the very foods we eat. All we have to do is avoid foods that provoke a “glycemic” response in the body, i.e. cause a rapid rise in blood sugar.
Inflammation has been found to be associated with just about every health condition. Researchers are furiously investigating chronic inflammation’s effects on health and possible preventive medical applications.
It’s “an emerging field,” says UCLA’s Dr. David Heber. “It’s a new concept for medicine.” (1)
Why is it a new concept? Because modern medicine focuses on treating symptoms, not addressing the root cause of an issue.Arthritis is inflammation of the joints. Heart disease is inflammation of the arteries. Instead of taking a medication to reduce joint pain or lower cholesterol, we would be better served by reducing inflammation in the body.
Dr. Tanya Edwards, director of the Center for Integrative Medicine, writes that inflammation is now recognized as the “underlying basis of a significant number of diseases.”
Although inflammation has long been known to play a role in allergic diseases like asthma, arthritis and Crohn’s disease, Edwards says that Alzheimer’s disease, cancer, cardiovascular disease, diabetes, high blood pressure, high cholesterol levels and Parkinson’s disease may all be related to chronic inflammation in the body.
What Inflammation is, and Why You Should Care
Just to make sure that we’re all on the same page, I want to briefly explain what inflammation is.
I’m not going to get into much detail, because inflammation is extremelycomplicated.
It involves dozens of cell types and hundreds of different signalling molecules, all of which communicate in immensely complex ways.
Put simply, inflammation is the response of the immune system to foreign invaders, toxins or cell injury.
The purpose of inflammation is to affect the function of immune cells, blood vessels and signalling molecules, to initiate an attack against foreign invaders or toxins, and begin repair of damaged structures.
We’re all familiar with acute (short-term) inflammation.
For example, if you get bitten by a bug, or hit your big toe on the doorstep, then you will become inflamed.
The area will become red, hot and painful. This is inflammation at play.
Inflammation is generally considered to be a good thing. Without it, pathogens like bacteria and viruses could easily take over our bodies and kill us.
However, there is another type of inflammation that may be harmful, because it is inappropriately deployed against the body’s cells (7).
This is a type of inflammation that is active all the time, and may be present in your entire body. If is often called chronic inflammation, low-grade inflammation, or systemic inflammation (8).
It is now believed that chronic, systemic inflammation is one of the leading drivers of some of the world’s most serious diseases (11).
However, it is not known exactly what causes the inflammation in the first place.
Bottom Line: Inflammation is the response of the immune system to foreign invaders, toxins and cell injury. Chronic inflammation, involving the entire body, is believed to drive many killer diseases.
Why Care About Omega-6 and Omega-3 Fatty Acids?
Omega-6 and Omega-3 fatty acids are called polyunsaturated because they have many double bonds (poly = many).
Our bodies don’t have the enzymes to produce them and therefore we must get them from the diet.
If we don’t get any from the diet, then we develop a deficiency and become sick. That is why they are termed the “essential” fatty acids.
However, these fatty acids are different than most other fats. They are not simply used for energy or stored, they are biologically active and have important roles in processes like blood clotting and inflammation.
Of course, inflammation is essential for our survival. It helps protect our bodies from infection and injury, but it can also cause severe damage and contribute to disease when the inflammatory response is inappropriate or excessive.
In fact, excess inflammation may be one of the leading drivers of the most serious diseases we are dealing with today, including heart disease, metabolic syndrome, diabetes, arthritis, Alzheimer’s, many types of cancer, etc.
Put simply, a diet that is high in Omega-6 but low in Omega-3 increases inflammation, while a diet that includes balanced amounts of each reduces inflammation (2).
The problem today, is that people who eat a typical Western diet are eating way too many Omega-6s relative to Omega-3s.
ROLE OF INTESTINAL FLORA
We may not realize that our intestinal flora can be a driver of inflammation. Gut-associated inflammation has been linked to insulin resistance, some forms of cancer, and even mental health concerns.
The trillions of bacteria that live within our gut have an intimate connection to our immune system, helping to strike a balance between tolerance and regulation. One type of bacteria that can cause inflammation is gram-negative bacteria.
GRAM-NEGATIVE BACTERIA INCITE INFLAMMATION
Some gram-negative bacteria exist naturally in a balance with gram-positive bacteria in our gut. But excessive or harmful gram-negative bacteria may appear due to an infection or in response to poor lifestyle choices, such as a high-fat, low-fibre diet.
Gram-negative bacteria have molecules in their cell walls called lipopolysaccharides (LPS), which are a little like a coat of gnarly armour. If the barrier function of the gut is diminished (which can result from a high-fat, high-sugar diet, stress, or other causes), these LPS can enter the bloodstream, where they incite an inflammatory response.
PROBIOTICS MAY REDUCE CHRONIC INFLAMMATION
While we see evidence that altered intestinal flora can lead to increased inflammatory markers, the ability of probiotics to reduce chronic inflammation is still being researched. In some studies, selected strains or blends of probiotic bacteria have outcompeted gram-negative bacteria. In addition, some probiotics have been shown to physically reinforce the gut barrier to prevent LPS passage. Through research to date, we see that certain probiotic strains within the Lactobacillus group are strong enough to act this way.
Some probiotic bacteria have also shown promise in reducing the production of messengers called pro-inflammatory cytokines. Probiotic bacteria produce substances known as short chain fatty acids, which can lower inflammatory markers in addition to strengthening the gut barrier.
Chronic inflammation can be debilitating, but it is not a life sentence. Inflammation is best addressed through an integrative approach to healthy living: eat more plants, move more, manage stress, and don’t forget to use beneficial bacteria to your immune advantage.
You know what inflammation looks like: You get a cut or bruise, and the area around it soon turns red, gets warm, and swells up. This is called the acute inflammatory response, and it’s your immune system’s defensive reaction to infection or injury. A complex array of immune cells congregate at the site and release a variety of chemicals to deal with the infectious organisms or debris from the injury and to allow tissue repair to begin; normally the inflammation gradually subsides. This immune response is essential to life.
But there’s another way inflammation works—it can be chronic and cause a low-grade systemic reaction. Because it increases with aging, it has been dubbed “inflammaging.” Chronic systemic inflammation has been the focus of a great deal of scientific attention during the past two decades (especially the past few years) and is now viewed as a sort of “unified field” explanation for many, if not most, age-related chronic diseases.
Accordingly, factors (genetic, lifestyle, and environmental) that promote chronic inflammation or disrupt the body’s protective mechanisms against it may increase the risk of premature aging and the disorders that go with it. On the other hand, healthy aging and longevity may be related to reduced levels of inflammation and/or strong protective mechanisms that guard against its adverse effects.
This was suggested by the results of a study in the Canadian Medical Association Journal last year, which included 3,000 British civil servants. It found a strong link between higher levels of chronic inflammation (as measured by blood levels of an inflammatory marker) and a decreased likelihood of “successful aging,” defined as optimal physical and cognitive health and the absence of chronic diseases. In fact, elevated levels of inflammation appeared to reduce the odds of successful aging by half over the next decade and to markedly increase the odds of cardiovascular disease and death.
Many complex roles
It can be both a cause andan effect of some disorders—setting up a vicious cycle that helps explain their chronic nature.
For example, chronic inflammation plays reciprocal roles with obesity and insulin resistance. It contributes to the development of insulin resistance, which in turn may help promote obesity. Conversely, obesity worsens insulin resistance and increases chronic inflammation, partly because body fat (especially the type surrounding internal organs) releases pro-inflammatory compounds. In effect, inflammation, obesity, and insulin resistance reinforce one another, often resulting in type 2 diabetes. What’s more, many lifestyle factors that promote inflammation, such as being sedentary and having an unhealthy diet, also promote obesity and insulin resistance.
Hard to pin down
Chronic inflammation is a varied phenomenon that affects nearly every aspect of human physiology and disease development. Many different kinds of specialized cells and chemicals are involved in producing and regulating these inflammatory processes.
Since it is so complex, there is no way to measure chronic inflammation directly. Instead, researchers measure a variety of inflammatory chemical markers in the blood or tissue, notably interleukin-6, tumor necrosis factor (TNF), C-reactive protein, prostaglandins, and leukotrienes. Elevated levels of these factors are good indicators of disease activity for some conditions (such as inflammatory bowel disease). But it’s not clear whether measuring them adequately gauges inflammation and the resulting risks for some other disorders (such as cancer).
Time for CRP Testing?
C-reactive protein, or CRP, is produced by the liver in response to inflammation. Of all markers for inflammation, it has gotten the most attention because research has shown that elevated blood levels are strongly associated with an increased risk of cardiovascular disease, even in people otherwise at low risk.
This was seen in the well-known JUPITER study a few years ago, which focused on people with desirable cholesterol levels but elevated CRP. It found that they greatly reduced their risk of heart attacks and strokes when they took a statin drug. Besides lowering LDL (“bad”) cholesterol, statins have anti-inflammatory effects, as seen in reductions in CRP.
Subsequently the FDA approved rosuvastatin—the statin used in JUPITER—for people who have desirable levels of LDL but high CRP and at least one other coronary risk factor. And according to revised cholesterol guidelines released last year, in cases where there’s uncertainty about statin treatment, CRP level is one of several factors that doctors should consider in making the decision.
Most doctors do not routinely measure CRP, however. It’s not clear what cutoff should be used to define high CRP, nor is it certain that bringing down elevated CRP will, by itself, be beneficial. Still, if you’re at intermediate coronary risk, and you and your doctor are on the fence about starting drug therapy, you should consider CRP testing. A high result could tip the balance toward a statin.
The link to heart disease
For many years atherosclerosis was seen as a kind of plumbing problem—that is, merely a matter of plaque building up in the walls of coronary arteries and clogging them. But blood vessels are nothing like pipes—they are active tissue involved in complex processes. In simplest terms, cells lining the vessels absorb cholesterol (and other substances) from the blood, leading to the build-up of plaque. The body perceives this plaque as an injury and sends inflammatory cells into the vessel walls, where they set off a cascade of events that can ultimately cause plaque to rupture and a clot to form over it. If the clot breaks off or otherwise obstructs blood flow to the heart or brain, this can result in a heart attack or stroke.
It now appears that inflammation plays key roles in all stages of the development of cardiovascular disease. Bacterial or viral infection may also trigger the inflammatory process in blood vessels. Meanwhile, coronary risk factors such as obesity, high blood pressure, undesirable cholesterol levels, and smoking cause or worsen arterial inflammation. Having an inflammatory disorder, such as rheumatoid arthritis, diabetes, or inflammatory bowel disease, also increases coronary risk.
Some medications that help prevent heart attacks and strokes, notably statins, do so at least in part by reducing inflammation. The story is more complicated regarding aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). At the low doses used to protect the heart, aspirin has only a small effect on inflammation; its heart benefit comes primarily from its ability to reduce the risk of blood clots. No other NSAIDs are good for the heart. In fact, some NSAIDs, notably celecoxib (Celebrex), increase the risk of heart attacks slightly.
The cancer connection
As early as the mid-19th century, scientists found links between chronic inflammation (or its markers) and cancer. It’s now estimated that more than 20 percent of cancer cases are associated with inflammation.
Inflammation is involved with cancer development on many levels. Notably, it contributes to tumor initiation by inducing oxidative stress, DNA damage, and chromosomal instability. It promotes tumor cell proliferation and resistance to apoptosis (programmed cell death after a certain number of cell divisions, a good thing when it comes to cancer cells). Simply put, increased inflammation makes it easier for normal cells to transform into malignant cells.
The evidence is strongest concerning gastrointestinal cancers, including certain kinds of colon, liver, esophageal, and stomach cancer. It’s theorized that these organs are at high risk because they are exposed directly to pro-inflammatory dietary and environmental factors. Inflammation can also alter colonic microflora in ways that increase cancer risk.
On the positive side again, evidence is accumulating that aspirin, partly because of its anti-inflammatory effect, can reduce the risk of certain types of colon cancer and possibly certain other cancers.
What does all this mean for you?
What can you do to reduce chronic inflammation and the risks it entails? There is no magic food, pill, or treatment. But many of the same steps that help prevent cardiovascular disease may do so in part by helping to tamp down inflammation.
- Eat a heart-healthy diet. Lab research has shown that many healthful foods, especially fatty fish, fruits, and vegetables (as well as chocolate, wine, and tea) have anti-inflammatory effects. Other studies have shown that the Mediterranean diet tends to reduce inflammation (as measured by CRP). On the other hand, saturated fats, trans fats, sugar, and other refined carbohydrates have pro-inflammatory effects in the body.
- Aerobic exercise, done regularly and moderately, reduces chronic inflammation via a variety of complex mechanisms. In contrast, being sedentary or training very intensely both increase inflammation.
- If you are very overweight, and especially if the extra pounds are in your abdomen, lose weight via a healthy diet and exercise. That will reduce inflammation and the risk of chronic diseases.
- Don’t smoke—it’s a powerful cause of inflammation. Avoid secondhand smoke.
- If you have had a heart attack or are at elevated risk for one, talk to your doctor about low-dose aspirin. If you have no history of cardiovascular disease, however, the risks of aspirin therapy (bleeding in the stomach or brain) may outweigh its small benefit. Similarly, if you are at high risk for colon cancer because of polyps or family history, discuss aspirin therapy with your doctor.
- If you’re prescribed a statin, here’s an added reason to take it: It serves double duty—against cholesterol and inflammation.
- Don’t drink more than moderate amounts of alcohol.
- Get adequate sleep and try to find ways to deal with stress, anxiety, and depression. Social isolation can also increase chronic inflammation, as was seen in a study in the Journal of Health and Social Behavior last year, so increasing social activities may help.
On the horizon: