Anti-ageing secrets: beat the drivers of ageing

written by The WellBeing Team

Anti aging secrets! Are you ready to unlock them? We might just be about to unravel the keys of aging and age-related diseases, such as cancer, Alzheimer’s and dementia. Central to this puzzle are three critical biological processes, which are inextricably linked. Uncovering how methylation, inflammation and glycation intersect and how they impact on the genes that determine how you age is critical. This knowledge might indicate how likely you are to succumb to degenerative and life-threatening illness and provide you with vital clues as to how you can intervene to prevent diseases and avoid the shortcomings of aging. Your anti aging quest will benefit greatly with this knowledge.

 

Anti aging & Methylation: the cell energiser

From your brain to your liver, from your hormone status to the lining of your cells, from your DNA to your RNA, methylation is the life force that determines how your cells are energized and is key to anti aging. To make brain chemicals such as serotonin, dopamine and noradrenaline, which affect your mood, your ability to concentrate and focus and your level of contentment, methylation is the core mechanism. If you are depressed, easily distracted and unmotivated, chances are you brain isn’t methylating in the best possible way. This will accelerate the aging process. Methylation is extremely important to anti aging.

Anti aging – methylation also determines whether your liver is able to adequately detoxify. It dictates your capacity to metabolise hormones such as oestrogen so that they become the kind of metabolites that look after you rather than cause harm. Your ability to take care of the lining of your blood vessels, called the endothelium, determines whether you will get heart disease or high blood pressure and is dependent on methylation. So how does this important process work and what is its relationship with anti aging?

Anti aging – methylation is the simple transfer of methyl groups (which contain one carbon and three hydrogen atoms) into an important amino acid called homocysteine. The production of homocysteine enables your body to make a complex called S-adenosylmethionine, also known as SAMe. SAMe is nicknamed “the universal donor”, which in some ways describes its overriding contribution to your wellbeing. Your body uses the methyl groups positioned on SAMe for a whole range of essential biochemical and cellular activities.

The manufacture of DNA and RNA is reliant on methylation and this is of critical importance. Methylation determines whether genes are switched on or off. Genes that are methylated are switched off while those that are unmethylated are switched on. This can be a good or bad thing, depending on which genes are turned on or off. Hypermethylation can rage like a rebel without a cause, making genes that influence normal cell growth produce proteins that cause malignant or unregulated cell growth.

Aging is thought to be a state of global hypomethylation, whereby a whole range of genes is activated. In the case of genes that have the function of preventing cancer, called “tumour suppressor genes”, this is unquestionably beneficial. Obviously, it is in your best interests to energise protective genes in order to combat the activity of a deadly process whose threatening presence looms larger with aging. Unfortunately, it’s a little more complex than this.

One of the major tumour suppressor genes, called P53, also has the added function of stimulating apoptosis, or cellular suicide. While this is advantageous if you can encourage cells with abnormal DNA to terminate themselves, healthy tissue can also be lost due to the activity of P53. This means that not only do you rid yourself of cells you don’t need but also you divest your body of healthy cells. In turn, this leads to tissue breakdown and the unwanted escalation of the degenerative process, which is synonymous with aging.

Anti aging: Maximising methylation

Folic acid and vitamin B12 are the prime contributors to methyl groups and you obtain these essential nutrients from your diet. Green vegetables cater for your folic acid needs, while animal products such as meat, salmon, sardines and egg yolk supply your vitamin B12 stores. To enter the methylation cycle, folic acid has to be activated via a number of biochemical steps and these all require energy. To manufacture this energy we need nutrients that include the B vitamins, zinc, magnesium, iron, manganese, the amino acid cysteine and coenzyme Q10. In my clinical experience, these nutrients often aren’t present in sufficiency, which makes it more difficult to facilitate the activation of folic acid and to transfer methyl groups ultimately to SAMe.

Are you vitamin B deficient? If you look at your tongue in the mirror and it has a strawberry edge or you have small cracks or sores at the side of your mouth, it’s likely you are low in B vitamins. Wounds that take a long time to heal or a poor sense of taste suggest zinc deficiency, while cramps in the lower part of your legs or constant flickering of your eyelids indicate magnesium is not serving you. These insufficiencies should be addressed through diet and supplementation to ensure adequate methylation takes place in your body. You cannot underestimate the importance of methylation to anti aging.

To promote methylation reactions and the delivery of methyl groups you need enzymes. Genetic defects, or what are known as “single nucleotide polymorphisms”, compromise the way this happens. They can be overcome by taking supplementary folic acid in high amounts or by using an alternative biochemical pathway, which utilises a food source called choline, found in beans and egg yolk. The ingestion of choline causes a knock-on effect that allows for the methylation of SAMe.

To find out how this biochemistry is playing out in your cells, your health practitioner can order tests that assess your gene polymorphisms, your nutrient levels (including vitamin B12, folic acid, manganese and iron via blood tests) and your zinc and magnesium status (via a 24-hour urine profile).

Another crucial substance that needs to be measured is homocysteine, as this amino acid is an intermediate on the way to the methylation of s-adenosylmethionne. If you have genetic defects with regard to enzyme polymorphisms or inadequate supplies of vitamin B12, folic acid or the other B vitamins (especially B2, B3 and B6), homocysteine will be inadequately methylated and it will start to accumulate in your bloodstream. This increases your risk of heart disease, raised blood pressure and Alzheimer’s dementia.

Status tests need to be ordered pre-emptively to prevent the biochemical payload of methylation defects. Initially, the most obvious signs may be emotional and mental health problems including depression and learning and memory deficits with deterioration of cognitive function. However, other often-silent fallout also occurs, with devastating consequences, such as the development of cancer.

The current trend towards fortifying foods with folic acid may contribute to methylation problems. Professor David Smith, who heads the Oxford Project to Investigate Memory and Aging in the United Kingdom, points out that supplementing with folic acid might prevent neural tube defects but also brings with it a number of adverse biochemical consequences. Pregnant mothers with high folate levels and low B12 status give birth to babies who have a greater chance of being overweight.

Smith also warns that too much folic acid circulating in the bloodstream might interfere with the enzymes that drive folate metabolism in the methylation cycle, which would jeopardise the way genes are methylated. This has ramifications for not only the development of obesity but also the origins of cancer and dementia.

 

Anti aging: The cancer–folic acid link

The connection between cancer and nutrient status is complex. Deficiencies of folic acid, vitamin B6, zinc and selenium have all been linked to methylation defects and the development of cancer. In this context, replacing folic acid lowers the risk of bowel cancer. However, animal studies on colorectal cancer have shown that the timing and dose of folic acid are paramount. If folic acid supplementation is started before the establishment of cancer, the development of the cancer is stifled, but once cancer cells have set up shop, taking extra folic acid will enhance the growth and progression of cancer.

In his review of this literature, Professor Smith highlights research showing that in a large study of 24,500 postmenopausal women, those who reported taking a high dosage of supplementary folic acid (more than 400ug/day) had a 19 per cent higher risk of breast cancer, whereas those whose intake was in the highest quintile (>835ug/d) had a 32 per cent greater risk of developing this cancer.

Folate is required for cell growth and division as well as DNA repair. Low folate status is associated with impaired DNA repair and adverse DNA methylation, which can be corrected with supplementation of folic acid. Once cancer is established, supplementing with folic acid can have the opposite effect, though. It helps cancer cells to replicate and can lead to methylation of tumour suppressor genes, which switches them off.

This means you should supplement with folic acid only if you are deficient. In the future, your methylation profile may also be assessed to determine intervention strategies and the nutrients you need to impact on the way your genes are expressed in a positive way. Laboratories around the world are developing techniques to assess genome-wide methylation and, although these aren’t freely available yet, their commercial reality is imminent.

 

Anti aging, Dementia and Alzheimer’s disease

If folic acid status poses a conundrum when it comes to preventing cancer, its relationship with dementia is even more problematic. Research out of the United States has revealed that elderly people with low vitamin B12 status and normal folate levels have a 70 per cent increased risk of cognitive impairment, whereas those with high folate levels and low vitamin B12 have an even greater risk. An imbalance of B12 and folate, especially elevated levels of folate, may interfere with the metabolism of folate and the methylation cycle. The end result? A loss of DNA methylation, leading to reduced adult neurogenesis or brain cell production and age-related declines in learning and memory performance.

The amyloid precursor protein gene is thought to contribute to the inherited form of Alzheimer’s disease. Switching on this gene leads to the accumulation of amyloid beta protein, which is associated with the brain tangles that develop in Alzheimer’s disease. Hypomethylation of the amyloid precursor protein gene occurs with ageing and might be connected with your folic acid or vitamin B12 status.

 

Anti aging: Inflammation and methylation

Chronic infection and inflammation contribute to up to 25 per cent of cancers worldwide. As an instigator of cancer growth as well as other aging diseases such as atherosclerosis and dementia, inflammation needs to be countered before its insidiously pernicious effects take hold. Free radical stress, in turn, increases inflammation, a silent process that can creep up on you. By the time you notice that malignant lump, suffer a heart attack from blocked blood vessels or can’t think properly because your brain cells are tangled and dysfunctional, your chance to save your life and wellbeing might be lost. That’s good reason to act now before it’s too late to intervene.

You can check your inflammation status by means of a blood test that measures HS-CRP or other inflammatory markers, identified by more specialised laboratories, including interleukin-6, or IL-6, and tumour necrosis factor alpha. If your HS-CRP test is elevated, examine the underlying causes of inflammation. The most common cause is being overweight, which is often associated with insulin resistance or the inability of the hormone insulin to facilitate the entry of sugar or glucose into your cells. This leads to glucose travelling around your bloodstream and causing all sorts of harm via a mechanism known as glycation.

Infection with germs such as Helicobacter pylori and Chlamydia pneumoniae (connected with inflammation of your blood vessels, which leads to heart disease) can also kickstart inflammation. Similarly, other causes include food allergy/intolerance, stress, elevated homocysteine, free radical overload, heavy metal stress (from metals such as lead, mercury, cadmium and aluminium) and a lack of protective germs in your bowel. These inflammation issues can be uncovered by doing the appropriate tests under the supervision of a health practitioner who recognises and appreciates the importance of diagnosing and addressing markers of inflammation before the problem takes complete hold.

 

Anti aging & Glycation: binding up your body

The process of glycation occurs when a sugar molecule binds to a protein, lipid or nucleic acid. There, it forms a molecule of irregular shape that your body can’t get rid of or metabolise normally. This reaction results in the formation of complexes known as Schiff bases and Amadori adducts. For example, when the haemoglobin that carries oxygen around your bloodstream becomes glycated or glycosylated, an unhealthy substance called HbA1C I is formed (this is measured to assess blood sugar control in diabetics). The Amadori adducts are then acted on by free radicals to form AGEs (advanced glycation end-products). AGEs disrupt protein-like collagen, leading to the ageing of your skin, and they damage the structures in your eyes, which diminishes your visual function. Even more lethal is the effect AGEs have on your blood vessels, dramatically intensifying your chances of succumbing to a heart attack, stroke and dementia.

What actually raises your blood glucose levels? Inadequate insulin function (see box). AGEs interact with a receptor to form RAGEs (receptors of AGEs). As its name suggests, this triggers a flurry of adverse biochemical reactions, including inflammation and heightened free radical stress. These, in turn, ignite atherosclerosis and the ageing of your brain cells. RAGEs reduce insulin function even further, intensifying this biochemical disaster by making more glucose available for glycation.

To bring this melodrama and the effects of glycation full circle, once glycation intensifies inflammation and the accumulation of free radicals, these then affect methylation adversely to age you prematurely and increase your risk of developing cancer. In light of this, it’s important to find out whether your blood glucose and inflammatory status are working for or against you with respect to methylation, one of the most vital processes in your body. Enlist the assistance of a health practitioner who knows how to evaluate these states so you can take the necessary steps to preserve methylation, which expresses your DNA in a healthy and vital fashion.

Anti aging & Damage control: limiting AGEs

We all know that eating sugar is not good for us, but the problems go far beyond weight gain and dental cavities. In tissues exposed to elevated blood sugar levels, toxic substances called advanced glycation end-products (AGEs) are formed. Eating browned food also increases your intake of AGEs, which substantially raise your risk of suffering a heart attack, stroke or nerve damage.

AGEs are increasingly being implicated in cellular damage, ageing and chronic disease. Once formed, they can crosslink with other strands of protein, causing a stiffening of tissues, for example, in the collagen of your skin and arteries or the protective myelin of your nerve proteins. Studies have shown that if intake of AGEs is cut in half, the lifespan of animals increases. To reduce your exposure to AGEs, keep in mind the following:

Anti aging & problematic cooking methods: Cooking foods with water prevents sugars from binding to proteins. However, when proteins and sugars are heated together in the absence of water (eg caramelising onions or baking a turkey), unhealthy AGES form. Baking, roasting and grilling cause AGES to form, while boiling and steaming prevents them. Brown foods, such as brown cookies, brown bread crust, brown basted meats and even brown coffee beans are detrimental. Fats or meat-derived products processed by high heat such as in grilling and oven-frying contain more AGE-generating substances than carbohydrates boiled for longer periods. Examples of foods that increase AGEs include roasted duck skin, fried and barbecued sausages, barbecued meat, roasted cashews, French fries, peanut butter, cream cheese, pancakes and foods that contain AGE-like caramel additives. The good old Aussie barbecue is one of the worst culprits. If you can’t give up cooking this way, make sure you marinate your meat, as the moisture helps reduce some of the levels of AGEs that are formed by the high heat.

Anti aging & the health issues associated with AGEs: AGEs accumulate in serum albumin (a transport protein made in the liver); lens crystallin, contributing to eye problems; and collagen, causing wrinkles. They accelerate ageing and are associated with cataracts, atherosclerosis, Alzheimer’s and Parkinson’s disease. What is most concerning about AGEs is they are not easily excreted, remaining in the body and exerting their destructive effects for at least three days after ingestion.

Anti aging – Helpful supplements to combat the effects of AGEs: Zinc, pyridoxamine, a B vitamin derivative, and thiamine may reduce AGE formation and the antioxidant carnosine may be beneficial because of its antiglycation effects. Aged garlic also appears to counter some AGEs’ formation and effects.

A quick fix: Reducing your food intake in what is known as caloric restriction also lowers AGEs. All you have to do is eat 10 per cent less daily.

 

Anti aging: Glycation and insulin

Insulin is the hormone that allows glucose to enter your cells. When your insulin function is compromised (insulin resistance), blood glucose goes up, which promotes unhealthy glycation. To discover whether you have insulin resistance, your health practitioner needs to conduct a two-hour test first thing in the morning after you have fasted overnight. Meanwhile, to reduce your risk of developing insulin resistance:

 


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