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Everyday Clinical Application of Telomere and Aging Support AnnAlisa Behling, N.M.D

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NUTRACEUTICALS S I N C E 1 9 7 2

EVIDENCE-BASED

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EVERYDAY CLINICAL APPLICATION OF TELOMERE AND AGING SUPPORT

ContentsIntroduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Natural Aging Cycles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Methylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Telomeres . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Mitochondrial function

and dysfunction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Integrative Approach to Anti-Aging Treatment . . . . . . . . 5

B2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

B6 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Folate. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

B12 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Trimethylglycine (TMG) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Dimethylglycine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Telomere Support Supplements . . . . . . . . . . . . . . . . . . . . . 8

Mitochondrial Function Supplements . . . . . . . . . . . . . . . . 9

D-ribose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

CoQ10 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Protocol for Anti-Aging Supplements . . . . . . . . . . . . . . . . 9

Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Biography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10


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Introduction Anti-aging should not be confined to external concerns like skin care. The general

health and life expectancy of a person depends on how well they age from the

inside out—from their skin, all the way down to their organs, mitochondria, and DNA.

Fighting aging from within leads people have a healthier aging process, which helps

them to live longer lives, avoid disability, costly elder care, and family strain in old age.

Anti-aging treatments target the natural processes that, over time, contribute to

aging on the cellular level. Integrative practitioners, especially naturopaths, know

anti-aging care is a natural part of health and wellness programs. In this white paper,

AnnAlisa Behling, NMD, explains how methylation, telomeres, and mitochondrial

function interplay in such a way that can either protect the body from aging, or

accelerate it. Behling also outlines supplement treatments that can boost these

cycles and play a role in a healthy lifestyle that promotes a healthier aging process.

Everyday Clinical Application of Telomere and Aging Support AnnAlisa Behling, N.M.D

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Natural Aging Cycles

MethylationThe most basic definition of methylation is an addition or removal of a methyl group

to a chemical compound. Although simple, the process of methylation is important

for biochemical reactions throughout the body. Methyl groups need to be added

or subtracted so enzymes can work, and so that production of different antibodies

and hormones in the body can take place. Methylation plays a primary role in phase

2 detoxification, which helps convert toxins into water soluble compounds that can

be excreted from the body. DNA methylation primarily takes place in the promoter

regions of transcriptionally active genes, resulting in the regulation of gene expression.

Methylation plays a big role in the body’s biochemical processes, and is crucial to aging at

the cellular level.

Lifestyle choices can greatly influence methylation. Alcohol abuse, the unhealthy modern

Standard American Diet (SAD), and smoking can all potentially interfere with methylation.

However, genetic differences between people can negatively affect methylation. For

example, some methylenetetrahydrofolate reductase (MTHFR) polymorphisms and single

nucleotide polymorphisms (SNPs) can impair folate metabolism, which is part of the

methylation pathway in the methionine cycle.

The folate cycle, the methionine cycle, and the methylation of DNA and RNA are all

interconnected. The methionine cycle makes S−Adenosyl Methionine (SAMe), which

is used to help produce DNA, RNA, hormones, and neurotransmitters. Meanwhile,

methyltetrahydrofolate works as a donor to methionine. The transsulfuration pathway

ends by making glutathione. TMG and DMG work with homocysteine to convert to

methionine, which leads to SAMe, and eventually to methylation products.

Anti-aging products may focus on CoQ-10 production, serotonin production, or

neurotransmitter production to improve energy, moods, or healing. But methylation all

comes down to the center of these anti-aging benefits, and has a huge influence on

immunity.

The folate and methionine pathways are critical when thinking about methylation. Folate

(B12) supplements, DMG supplements, and TMG supplements all contribute to these

pathways. What happens in these pathways affects how the body functions on a cellular

level. In turn, what happens at the cellular level affects the organs and the external health

of a person such as the appearance of their skin, hair, and nails.

TelomeresMethylation is central part of the aging process, but another biological process involved

with aging that has gained widespread recognition and understanding in the past 20

years is telomeres. In 2009, Elizabeth Blackburn and Jack Szostak received the Nobel Prize

for their work in telomeres. These scientists identified that telomeres weren’t coding

THE MOST IMPORTANT

CYCLE IN AGING

Methylation drives telomere health

Telomere dysfunction results in mitochondrial

dysfunction

Mitochondrial dysfunction then results

in hypomethylation

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genes, but caps to the ends of the DNA strand of a chromosome.

Every time a cell divides, a chromosome degrades. Blackburn and

Szostak found that telomeres functioned to protect the rest of the

chromosome from degrading.

The sequence of the telomeres is TTAAAGGG. Telomeres allow DNA

to replicate fully by protecting DNA through the enzyme telomerase.

The problem is that telomeres shorten each time a cell divides, so the

telomerase act to lengthen the telomere. There is a shortening of the

telomere with every replication, and there is a re-lengthening with

telomerase, sort of like a slinky.

While telomerase can work very well, the DNA code for the telomeres

doesn’t fully replicate each time a cell divides. This means the

telomeres continue to shorten with each cell division. As they shorten,

they don’t protect the chromosomes. Shortened telomeres can still

offer some protection, but there is a critical length where the cell

function becomes impaired and one step closer to death.

Once telomeres reach the critical length, the cell is said to have

reached the Hayflick limit where cells can only continue to divide

and replicate a certain number of times before the cell either dies or

becomes senescent and division halts. In this case, it is preferable for

a cell to die rather than become senescent. When a cell is senescent,

it continues to live, but can damage other cells with inflammatory

cytokines.

At birth, the average white blood cell telomere is 8,000 base pairs long.

In the elderly, there are only about 1,500 base pairs in the average white

blood cell telomere. That’s how much those telomeres have shortened

by cell division over a lifetime. Today, people who are interested in anti-

aging can get their telomeres tested.

One way to visualize telomeres is to think of shoelaces. Shoelaces are

protected from fraying with plastic caps at the end, just as the DNA in

chromosomes are protected with telomeres at the end.

As shoelaces get old from tying and retying, the caps on the end

degrade and eventually the shoelaces start to fray.

Telomeres have become a new aging hypothesis of sorts. Other older

theories as to how we age focus on reactive oxidative species and

mitochondrial damage. However, it’s only been in the last decade

or so that telomere shortening has emerged as an aging theory.

This theory has produced a lot of research. There are now more than

10,000 research studies on telomeres and their function in health,

aging, and cancers.

One recent study from Johns Hopkins found critically short telomeres

in the early stages of pancreatic tumor necrosis. It may be possible to

one day use telomere length as a risk factor. For example, if someone

has critically short telomeres and pancreatic issues in their family

history, perhaps they could be monitored for signs of cancer and

catch it early.

Mitochondrial function and dysfunctionMitochondria are crucial to cell survival, cell death, and aging.

Mitochondria are central to the energy production in the body via

two processes. First is the citric acid cycle, more widely known as the

Krebs cycle. The second is oxidative phosphorylation (OXPHOS), which

provides 80 percent of the body’s energy stores.

Unfortunately, like telomeres, mitochondria can get damaged. Free

radicals can damage the mitochondrial DNA and lead to decreased

efficiency of the Krebs cycle. Respiratory chain defect and membrane

disorganization can also impact mitochondrial function.

Mitochondria are so crucial that if the organelle experiences

mitochondrial damage or failure, it can lead to cell death. And if

multiple cells die off or become senescent due to mitochondrial

damage, it can even lead to organ failure.

Integrative Approach to Anti-Aging Treatment The United States is currently undergoing a population shift. In 2000,

only 10 percent of the population was over 60 years old. But by 2050,

more than 21 percent of the population will be over 60 years old.

The concern becomes whether people will age well, which should

be a priority for integrative physicians, health coaches, nutritionists,

naturopaths, chirpractors, and medical doctors working with this

population.

Aging is a multifaceted process. There are contributing gerontogenes,

telomeres, cell cycle replication, cancers, DNA damage, and repair

issues. In addition, there are mitochondrial issues, signal transductions,

and DNA and RNA processes that affect aging internally. Externally,

environmental issues, food choices, and lifestyle will affect how an

individual ages.

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Supporting patients as they age requires practitioners to take these

factors into account. Integrative physicians should identify if someone is

aging poorly, and where their diet, supplementation, and other lifestyle

choices are taking them. Methylation Supplements

An anti-aging supplement that directly targets methylation should include

B2, B6, B12, trimethylglycine (TMG), and Quatrefolic®, which is a special

folate. . TMG, betaine, is a methyl donor. The combination of B6, B12, and

folate can improve the health and size of the hippocampus, as well as

overall brain function. Even in the case of someone with Alzheimer’s, this

combination can start to repair gray matter that has atrophied.

B2B2, or riboflavin, is needed for the body to convert almost all other B

vitamins for use in the body. B2 is critical for the utilization of B6, which is

a required element of the folate cycle.

B6B6 is necessary to create glutathione—an important antioxidant in the

body—because it’s essential to the transsulfuration pathway. However, B6

is needed everywhere in the body in more than 100 enzymatic reactions

necessary to normal brain function, to nerve function, to the synthesis of

neurotransmitters, and to lipids in the myelin sheath.

FolateAlthough folic acid has long been a popular supplement, it’s not

guaranteed that every person will benefit from it. There is a substantial

portion of the population that has SNPs, polymorphisms, or issues with

their MTHFR, and so will have trouble converting folic acid into folate.

Folate is a key source of the one carbon group used to methylate DNA.

Instead of using folic acid, good anti-aging supplements will have

bioavailable, body-ready folate, such as Quatrefolic®.

B12B12 is known to boost energy, and is also useful to maintain methylation,

therefore working as an anti-aging supplement. Methylation makes

nucleic acids, hormones, and neurotransmitters—the body cannot

function without methylation.

B12 is involved in the methionine cycle. Methylcobalamin, the active form

of B12, is used to make methionine synthase enzyme, which converts

homocysteine to methionine in the methylation pathway.

VITAMIN B2• Most formulas do not contain the Riboflavin-5-Phosphate

form due to instability and cost

• B2 helps the body convert other B vitamins for use, and is critical for the utilization of B6 and is also a required element of the folate cycle

VITAMIN B6• B6 is a required element of the folate cycle (see diagram)

• Formula contains both Pyridoxyl-5-Phosphate and pyridoxine HCl

• The trans-sulfuration pathway, where cystathionine breaks down to cysteine (a glutathione precursor) is B6 dependent.

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Methionine conversion is essential to SAMe production. SAMe is the

primary metabolic methyl donor, which donates a methyl group

to molecules such as phospholipids, neurotransmitters, and DNA.

DNA methylation represents the means of epigenetic control of

gene expression. Ideally, an anti-aging supplement should include

methylcobalamin, an active form of B12, so that the body does not have

to reconvert poorly-absorbed B12.

B12 is an important supplement for overall health, but especially for

people who are vegan or vegetarian. Meatless diets require careful

addition of protein to include enough B12, so supplementation is often

necessary. A B12 deficiency can result in intracellular deficiency of

tetrahydrofolate.

Trimethylglycine (TMG)Trimethylglycine (TMG) is also known as betaine. It’s a predominant

methyl donor in the body and supports the body’s natural production

of SAMe in the methionine cycle. TMG allows homocysteine to be

re-methylated to methionine, which makes SAMe. The methionine

cleaves a methyl group from TMG turning it from trimethylglycine to

dimethylglycine, or DMG.

DimethylglycineDimethylglycine (DMG) is a natural-forming product in the body. It is

formed when TMG donates a methyl group. DMG then becomes a methyl

donor to the folate cycle.

DMG is included in anti-aging supplements and is a metabolic enhancer,

an adaptogen, and helps the body overcome stress. It is used in oxygen

utilization, detoxification, circulation, fat metabolism, brain function,

and immunity. DMG affects both the humoral and the cell-mediated

immunity and it helps produce antibodies, cytokines, and lymphocytes.

It is involved in free radical damage repair, increases ATP, and is used to

increase endurance and stamina.

Research on DMG and TMG has shown a wide variety of benefits.

Astronauts have been known to take DMG before going up in space, and

studies have found those who take DMG before space missions come

back with lower radiation levels than those who didn’t take DMG. Early

research in rats also shows DMG may protect against liver damage from

alcohol.

TRIMETHYLGLYCINE

One of the body’s predominant methyl donors, is known for supporting the body’s natural production of SAMe, during the Methionine Cycle.

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Telomere Support Supplements Early research has shown several plant-based ingredients can support

telomere health, such as Astragaloside IV, which is derived from Astragalus.

An herbaceous perennial, Astragalus is a member of the pea family. It’s

been used in Chinese traditional medicine for thousands of years. Recent

research has shown new potential of Astragalus in modern medicine.

A 2013 review in the Journal of Traditional Chinese Medicine found that

Astragaloside IV has applications in cardiovascular diseases, digestive

diseases, cancers, and other high-risk diseases. A 2012 review in Plant

Medicine demonstrated how Astragaloside IV supported the immune

system. Astragaloside IV demonstrated specific support to the immune

system by improving CD8+ T lymphocytes responses via upregulation

of telomerase activity. The study found both Astragaloside IV and

cycloastragenol initiated the phosphorylation of extracellular signal

regulating kinases. Compounds like Astragaloside IV are telomerase

inducers, and are a natural herb from a natural source.

Other anti-aging plants and plant-derived compounds useful for

telomere health include broccoli sprouts, green tea catechins, curcumin,

pomegranates, lycopene, quercitin, and polygonatum, which is part of the

buckwheat family.

A 2014 study in PLOS ONE found curcumin was especially helpful for the

enzyme telomerase. This study focused on the impact curcumin has on

human telomerase reverse transcriptase (hTERT) , the catalytic subunit of

the telomerase enzyme. RNA interference results in a significant increase

in oxidative stress and cell toxicity, and a decrease in hTERT. Curcumin was

able to upregulate the expression of hTERT, thus providing a viable strategy

for supporting telomerase activity. Since curcumin can likely support

telomerase activity, it is now included as part of Astragaloside to help

boost telomere health and fight aging.

Curcumin has a long history in promoting health. Curcumin, found in

ginger and turmeric, has been used for thousands of years in Ayurvedic

medicine and in many Asian cultures. Recent studies have shown it has

an impact on everything from anti-aging and anti-cancer activity to brain

health and oxidation health.

Green tea and the compound quercitin was recently found to reduce

telomere shortening. In an animal study published in 2013 in the

International Journal of Cardiology, overload-induced cardiac hypertrophy

initiated oxidative stress, telomere repeat binding factor 2 loss, and

telomere shortening. However, ECGC and quercetin inhibited the loss

DIMETHYLGLYCINE

DMG is synthesized from betaine during the remethylation of homocysteine to methionine, catalyzed by BHMT.

DMG donates a methyl group to the Folate Cycle and from there the remethylation of SAMe, which in itself is a methyl donor.

Astragaloside IV has broad application prospects, especially in cardiovascular diseases, digestive diseases, cancer and other modern high incidence, high-risk diseases, and could be developed as a medicine.

Journal of Traditional Chinese Medicine, June 2013 Pharmacological effects of Astragaloside IV:

a literature review.

ASTRAGALOSIDE IV

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of telomere repeat binding factor 2 (TRF2), and were effective at

supporting healthy telomere lengths.

Supplement products that combat the telomere-shortening

aspect of the aging process will likely include plant-derived

compounds like astragaloside, green tea, or curcumin. Supplement

manufacturers can’t make a product for every food that can fight

aging. A healthy diet with a variety of anti-aging foods, such as

broccoli, asparagus, B2-rich foods like spinach, fish oils with DHA for

the brain and EPA for anti-inflammation is key. If a patient is hesitant

to change their diet, they should be made aware of anti-aging foods

they can incorporate into their current lifestyle.

Mitochondrial Function Supplements Anti-aging nutritional supplements that support mitochondrial

function are likely to have a range of ingredients. For example, they

may include natural sugar called D-ribose, the compound acetyl

L-carnitine, and malic acid. DMG as well as Rhodiola, Coenzyme Q10

(CoQ10), bromelain, and proteases are also beneficial ingredients in

anti-aging supplements.

D-riboseA recent study in the Open Pain Journal found D-ribose had wide-

ranging benefits. The open-label, non-blinded study followed

257 people who had been given a diagnosis of chronic fatigue

and fibromyalgia. Of the original 257 in the study, 203 patients

completed the three-week treatment trial. D-ribose treatment led

to statistically significant clinical improvement in overall wellbeing

(37 percent increase), in sleep (29.3 percent improvement), mental

clarity (30 percent improvement), pain (15.6 percent decrease), and

a 61.3 percent increase in energy.

CoQ10A 2014 study in the journal BBA Clinical found a strong link between

mitochondrial dysfunction and low CoQ10 levels. The review

examined studies that investigated the association of mitochondrial

dysfunction markers with fatigue, and proposed possible research

directions to enhance understanding of the role of mitochondrial

dysfunction in fatigue.

CoQ10 was the most commonly investigated mitochondrial

enzyme in the studies reviewed, and low levels of CoQ10 were

consistently associated with fatigue. Carnitine was the most

investigated mitochondrial function marker, and dysfunctional

levels were reported in all the studies investigating carnitine.

Unfortunately, CoQ10 gets used up very easily in the body if

someone is taking medications. Statin drugs, for instance, are a

huge issue for CoQ10. It’s important to help patients maintain

CoQ10 levels when the body can’t get it from nature, whether it’s

through food or through a supplement.

Protocol for Anti-Aging Supplements Most people seeking anti-aging care can take just one capsule

of a supplement per anti-aging method, once or twice a day. For

telomere health, taking one capsule of a telomere supplement

once or twice daily and one capsule of a phytonutrient supplement

once a day should help. For improved methylation, one capsule of

a methylation support supplement once a day, and one chewable

tablet of a DMG supplement once or twice a day should help.

DMG can be recommended in amounts ranging from 125-500 mg

and can be taken in liquid form. All these anti-aging supplements

will also help mitochondria function, but specific mitochondria

supplements have been shown in research papers to offer

particularly good mitochondrial support. Normally, dosage can be

roughly one scoop a day, with alterations depending on how active

a person is.

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Conclusion Aging is a universal concern. While aging is inevitable, how

individuals and their health care providers approach aging may

influence whether they age healthfully and live well, or whether

they face old age in poor health and disability. Diet, exercise, alcohol

use, and genes can all play a role on how well individuals age. With

recent research, integrative physicians now have several avenues

of anti-aging treatment that work on the cellular level. Telomeres,

mitochondria, and methylation are three such techniques.

Supplements that support telomere health typically boost or protect

telomerase, the enzyme that protects telomeres. Telomeres, in turn,

protect dividing cells from DNA damage. Supplements that support

mitochondrial function typically provide energy and improve mood

while protecting against mitochondrial-induced cell death and

aging. Supplements that protect and boost methylation include

elements of the crucial folate and methionine pathway, such as B6

and B12. In turn, better methylation will improve brain function and

overall health.

Aging is not just about one idea of oxidation, or mitochondrial

dysfunction, or cell damage, or environmental decay. All these cycles

work together. This overarching aging cycle can be targeted both

internally and externally with treatment. If patients want to grow old

and age gracefully, then including supplements alongside an anti-

aging diet and lifestyle measures should be a common treatment in

integrative practitioner offices.

Biography AnnAlisa Behling, N.M.D., earned her bachelors in psychology at

Duke University in Durham, NC, and her doctorate degree from

the National College of Naturopathic Medicine in Portland, OR. She

practices general family medicine with an emphasis on natural and

complementary therapeutics, and serves as a medical advisor for

DaVinci Laboratories.

Behling is clinically trained and experienced in nutritional medicine,

homeopathy, hydrotherapy, oriental medicine, naturopathic

manipulation, low-level laser therapy, physical medicine, and

botanical medicine as well as psychological and lifestyle counseling.

Documents

AnnAlisa Behling, N.M - davincilabs.com · B2, or riboflavin, is needed for the body to convert almost all other B vitamins for use in the body. B2 is critical for the utilization