How Glycation Accelerates AgingMay 2017
By Stuart Chan
Diabetics suffer accelerated aging and early-onset of degenerative illnesses.
An underlying culprit behind diabetic complications is tissue glycation.1
Glycation occurs when blood glucose links to proteins in the body. The pathologic impact is formation of advanced glycation end products that wreak systemic havoc.2-9
Those with poor sugar control suffer dangerously high glycation levels. These same toxic glucose reactions occur in nondiabetics, but at a slower pace.
For the past 14 years, Life Extension Magazine® has advised readers to avoid or reduce intake of food cooked at high temperatures. The reason is, when you eat these heat-damaged proteins, they inflict glycation damage to your body’s proteins. This is in addition to glycation that occurs as a result of life-long glucose exposure.
In this article, we provide a targeted strategy to defend against glycation-induced tissue damage.
What is Glycation?
Glycation is a process by which sugar molecules react chemically with proteins in the body, causing the proteins to cross-link and lose their functionality.2
Not only does this cross-linking prevent proteins from doing their intended jobs, it creates harmful molecules called advanced glycation end products (or AGEs).3
The acronym AGEs is appropriate considering these toxic protein reactions are a root cause of premature aging.
Ultimately, glycation causes inflammation that damages mitochondria, while mitochondrial dysfunction exacerbates glycation. This result in an age-accelerating cycle as glycated proteins accumulate in tissues throughout the body.4,5
Mitochondria and Aging
The human body depends on sugar and oxygen to provide the energy that keeps its heart beating and brain thinking. Intracellular powerhouses called mitochondria work wonders by using glucose, fatty acids, and oxygen. The result is life-giving energy that powers every aspect of the body.
But, like other forms of energy generation, the process produces reactive molecules as byproducts that build up and damage the very cells, tissues, and organs the process is meant to support.
Glycation also damages molecules vital to life, like DNA, enzymes, and structural proteins.
Progressive glycation leads to reduced mitochondrial energy production and increased oxidative stress. Eventually, damaged mitochondria can stop functioning altogether, producing an age-related energy crisis that speeds up and worsens the aging process.6
This is one reason why, as we age, we not only move and think more slowly, but we also repair damage to cells and DNA more slowly, if at all. All of those actions require energy, which is in increasingly short supply.
Impact on the Body
Together, mitochondrial dysfunction and glycation have a disastrous effect on the body’s systems, and are responsible for many symptoms of aging. Here is a partial list of the types of damage they wreak on the body:
- The accumulation of advanced glycation end products (AGEs) can contribute to kidney disease and renal failure. When AGEs accumulate in the filtering portions of kidneys, it reduces the ability to excrete waste.7
- AGEs can lead to neurodegenerative diseases like Alzheimer’s and Parkinson’s because they contribute to the formation of cross-linked proteins. These damaged proteins accumulate in cells, disabling and eventually killing brain cells.8,9
- When glycation occurs in the skin, it sensitizes the skin to ultraviolet (UV) radiation, triggering oxidative stress that damages DNA and increases the risk of skin cancers.10
- AGEs damage joint cartilage, resulting in stiffening and loss of ability to handle stresses. AGEs are now recognized as major contributors to osteoarthritis.11
- When similar AGE-related damage occurs in spinal discs, it can make disc injury and herniation (“slipped disc”) more likely.12
- Glycation is especially damaging to our eyes. Not only does it lead to clouding of the lens (cataracts), it also causes retinal damage—both of which impair vision and ultimately produce blindness.13,14
- The protein-rich walls of arteries, and even tiny capillaries, are especially vulnerable to glycation-induced damage.15 The resulting stiffening and inflammatory changes produce atherosclerosis, the cause of heart attacks, strokes, and other vascular disorders of aging.4
In short, glycation, linked to poor mitochondrial function, accelerates every aspect of human aging.
While we are exposed to glycation on a daily basis, we are not helpless in the face of its destructive effects. A huge volume of published data support the use of specific nutrients that work hand-in-hand to reduce glycation and its effects, while also supporting healthy, energy-producing mitochondria.
Four compounds have been identified to reduce the rate of glycation and control the consequences when it occurs.
The first is a fat-soluble form of vitamin B1 (thiamine) called benfotiamine.16,17 Lab studies have shown than benfotiamine can prevent glycation, and human studies have shown that it can help prevent the damage caused by glycation.16,18
In a study of type II diabetics, benfotiamine helped prevent blood-vessel damage caused by glycation. For the study, subjects ate a meal high in AGEs (caused by high-heat cooking), then took benfotiamine for three days, and then ate the same high-AGE meal again.18
Initially, the AGE-rich meal reduced blood flow throughout the subjects’ bodies as a result of the impact of AGEs on blood vessels. But after supplementing with benfotiamine for just three days, blood flow measurements completely normalized, demonstrating just how quickly benfotiamine exerts its powerful impact.
A later study of diabetic animals further demonstrated the ability of benfotiamine to improve heart and blood vessel function, while also reducing death and scarring of vital heart cells.19
Lab studies have given us insight into how benfotiamine works to prevent glycation itself, as well as the damage it can cause. Through at least three biochemical pathways, benfotiamine has now been shown to improve function of tiny capillaries in the retina, increase mitochondrial energy production in muscle cells, protect against kidney and other tissue damage in dialysis, and prevent DNA damage.17,20-24
Pyridoxal 5’-phosphate is an active form of vitamin B625 that is receiving growing attention as a natural complement to benfotiamine. Like benfotiamine, this active form of vitamin B6 has the dual benefit of helping prevent glycation as well as its harmful effects (such as the buildup of gunked-up proteins and AGEs).26,27
Pyridoxal 5’-phosphate is one of the most effective compounds known to inhibit glycation of fats (lipids) and proteins.28 This is an important protective function, since lipid glycation is a major threat to the function of cell membranes, which is an underlying factor in numerous age-related conditions.29,30
This metabolically active form of vitamin B6 (pyridoxal 5’-phosphate) works by essentially trapping glucose breakdown products before they can participate in dangerous glycation reactions.25
Luteolin is a flavonoid found abundantly in many plants. Since one of the main consequences of glycation is inflammation, luteolin’s anti-inflammatory properties make it an ideal natural complement to benfotiamine and pyridoxal 5’-phosphate. Inflammation is widely recognized for its association with cancer, atherosclerosis, and virtually all other chronic diseases.31
Luteolin works by suppressing the activation of the master inflammatory complex called NF-kB, which triggers the production of a wide variety of pro-inflammatory signaling molecules (cytokines).
The anti-inflammatory actions of luteolin have been demonstrated in tissues throughout the body, including the brain, blood vessel lining, skin, intestines, lungs, gums, and bone.32-39
A study published in the American Journal of Respiratory and Critical Care Medicine gives us insight into how monumental luteolin’s anti-inflammatory impact truly is. When mice were exposed to a bacterial toxin, only 4.1% of them survived. But when mice that were given luteolin were exposed to the same toxin, it promoted survival in 48% of the mice.40
Carnosine is a potent free-radical scavenger and anti-glycating agent that inhibits AGE formation and its cross-linked proteins, helping to keep them functioning properly.41-44
Carnosine has powerful lipid glycation-preventing properties and profound impacts on fundamental AGE-signaling pathways, making it a highly promising anti-aging drug candidate.45
Studies show that carnosine prevents protein cross-linking and the accumulation of the tangled protein clumps associated with Alzheimer’s disease.46,47
Carnosine has also been shown to lower blood-lipid levels, reduce the metabolic stress induced by high-fat diets, and, very importantly, to help stabilize atherosclerotic plaques, reducing their risk of rupturing and triggering a heart attack or stroke.15,48
Finally, carnosine works in numerous ways to help protect mitochondria from the destructive effects of cellular oxidative stresses.43
Nutrients that Enhance Mitochondrial Function
As we discussed earlier, preventing glycation is one piece of the puzzle. It is equally important to preserve mitochondrial function in the face of glycation-induced damage. Three unique compounds have been identified in the scientific literature that can lend new life to aging mitochondria.
Pyrroloquinoline quinone (PQQ)
Pyrroloquinoline quinone (PQQ) is a vitamin-like molecule that promotes the production of new mitochondria in cells, helping to restore cellular energy.6,49 The result of insufficient cellular PQQ is reduced numbers of mitochondria.49
In a clever experiment, researchers treated animals with a toxic chemical that induces Parkinson’s disease-like symptoms. They then fed the rats a probiotic made of bacteria that had been engineered to produce PQQ.6
Initially, the chemically-treated rats lost mitochondria and showed obvious evidence of oxidant damage in their organs. But after receiving the PQQ-supplying probiotic, those changes were reversed, new mitochondria formed, and the animals recovered from severe metabolic damage.
R-lipoic acid is essential to enzyme systems involved in extracting energy from food.50,51 This makes it vital for efficient mitochondrial function.
Studies show that giving older animals R-lipoic acid leads to improved metabolic function, healthier mitochondria, and reduced production of oxidative stress-inducing byproducts.
In addition, animals supplemented with R-lipoic acid age more slowly than they otherwise would. This is because R-lipoic acid also protects liver, heart, and brain cells from mitochondria-induced oxidative stress.52-58
Due to these abilities, R-lipoic acid is emerging as a popular anti-aging supplement.
Taurine is an amino acid that has been found in extremely high concentrations inside mitochondria, where it regulates the enzymes responsible for harvesting energy from food molecules.59
Because of this important function, taurine is found most abundantly in heart and skeletal muscle, brain tissues, and the retina—all of which have extremely high metabolic rates that burn out mitochondria.60-63
Insufficient taurine in these tissues produces an energy crisis that results in accelerated aging.64,65 The good news is that adding taurine back to such cells in crisis can reduce oxidative stress and maintain – and often restore – mitochondrial function in aging cells.62,63,66
Indeed, taurine is one of the few nutrients capable of spurring brain cells to put out new shoots, called neurites, enhancing brain cell connections that preserve cognition and memory.67
Glycation of our body’s tissues is a normal consequence of aging. Those with poor blood sugar control suffer more glycation reactions and prematurely age.
Ultimately, glycation and mitochondrial dysfunction together produce ever-faster aging.
Fortunately, scientists have uncovered several nutrients that function to support healthy mitochondrial function while reducing glycation and its damaging effects.
These nutrients work together to rejuvenate cell energy levels while reducing tissue damage.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.
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- Hipkiss AR. Aging risk factors and Parkinson’s disease: contrasting roles of common dietary constituents. Neurobiol Aging. 2014;35(6):1469-72.
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- Verzijl N, DeGroot J, Ben ZC, et al. Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: a possible mechanism through which age is a risk factor for osteoarthritis. Arthritis Rheum. 2002;46(1):114-23.
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- Tarallo S, Beltramo E, Berrone E, et al. Human pericyte-endothelial cell interactions in co-culture models mimicking the diabetic retinal microvascular environment. Acta Diabetol. 2012;49 Suppl 1:S141-51.
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