This is the sixth post in a series about slowing and reversing biological aging. The first five posts are:

1. 7 Steps to Slow and Even Reverse Aging
2. Regenerating the Thymus Gland and Immune Function
3. Understand Your Aging Process: The 12 "Hallmarks of Aging"
4. Combat Aging with 16+ “Youth Factors”
5. Should You Restrict Protein, Carbs, and Calories, or Eat More as You Get Older? AMPK, Autophagy, and mTOR

Keep Your DNA Young

Since your DNA provides most of the information for the form and function of your body, it would probably come as no surprise to you that DNA is heavily involved in aging and longevity. This post covers three ways to empower your DNA to keep you young: activating sirtuins, optimizing DNA methylation, and maintaining telomere length.

Activate Sirtuins

Sirtuins are seven proteins that promote healthspan and lifespan in a variety of ways. So the genes that code for these proteins are sometimes called the "longevity genes". Here are some of the actions of the sirtuins.

1. Repair DNA
2. Increase mitochondrial biogenesis
3. Increase autophagy (recycling of damaged cells and cellular components)
4. Increase apoptosis (programmed cell death, important for cancer prevention)
5. Activate the production of certain antioxidant enzymes like superoxide dismutase
6. Reduce inflammation
7. Stimulate signaling between the nucleus and the mitochondria in cells
8. Stimulate signaling between the hypothalamus and fat cells

As you might surmise from the list above, sirtuins are involved in many processes that affect whether you stay healthy or develop disease. In fact, healthy sirtuin function and expression (avoiding underexpressoin or overexpression) appears to be involved in preventing many diseases, including Alzheimer's disease, cancer, heart disease, diabetes, osteoporosis, muscle wasting, and macular degeneration, 

The word "sirtuin" comes from acronym, SIR, that derives from the expression "silent information regulator" (SIR). DNA provides genetic information. "Silent information" is genetic information, genes, that are silenced by various mechanisms such as methylation in order to maintain healthy cell function.

Sirtuins are enzymes that sit in particular places on your DNA in order to maintain normal gene expression. The regulation of gene expression via mechanisms like methylation and sirtuin activity is referred to as "epigenetics". 

Sirtuins also have other functions, like DNA repair and control of inflammation and oxidative stress. These other roles call sirtuins away from their role in maintaining normal epigenetic regulation of gene expression in cells.

So over time, as sirtuins get distracted from their role of maintaning normal epigenetic control of DNA expression, a cell can lose some of its unique programing, effectively losing its identity and drifting into less healthy patterns of function.

Harvard researcher on the science of aging, David Sinclair, PhD, one of the world's leading researchers on the aging process, believes that this degeneration of epigenetic regulation characterizes the aging process at its core.

The first step in optimizing sirtuin function is to reduce the inflammation and oxidative stress that distracts sirtuins from their role of maintaining normal DNA expression. The second step in optimizing sirtuin expression is to give sirtuins what they need to function.

Sirtuins require NAD+ in order to function normally. NAD+ is the oxidized form of nicotinamide adenine dinucleotide, which is derived from niacin (vitamin B3). By age 50, most humans have only 50% of the NAD+ they had in their youth. With a lower level of NAD+ sirtuins cannot work as well as they did earlier in life.

So you have probably heard a lot in the longevity space about taking NAD+ precursors like nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) in order to increase NAD+ levels. And now "infusion" bars are springing up, offering IV therapies, including IV NAD+. But keep in mind that you can raise NAD+ with humble niacinamide, a "non-flush" form of niacin (B3) and by improving the recycling of NAD+.

Just realize that when taking any of these forms of niacin, the body uses methyl groups from S-adenosylmethionine (SAM) to process extra niacin, so sufficient SAM needs to be present when supplementing with high doses of any form of niacin. Some people have low levels of SAM or an inability to utilize SAM due to elevations of a competing molecule, S-adenosylhomocysteine (SAH) and therefore should improve the function of their methylation cycle when supplementing with high doses of niacin. One way to do this is by taking extra methyl groups via trimethylglycine (TMG), a.k.a. betaine anhydrous.

In addition to impairing sirtuin function, low NAD+ blunts the response to exercise, so this may be yet another reason that people over 50 tend to have to work harder to gain the benefits of exercise, such as muscle growth. Other causes of this blunted response to exercise include elevated cortisol, inflammation, and reduced responsiveness of mTOR, as discussed in the previous post, Should You Restrict Protein, Carbs, and Calories, or Eat More as You Get Older? AMPK, Autophagy, and mTOR..

While increasing NAD+ to youthful levels may promise youth-promoting benefits, too much NAD+ suppresses sirtuins. As with everything, balance is key. 

Two of the most important sirtuins are sirtuin 1 (SIRT1) and sirtuin 6 (SIRT6). David Sinclair, PhD has focused much of his research on activating SIRT1 with resveratrol, but other phytonutrients like fisetin, quercetin, and piceatannol also activate SIRT1.

Thus far, the research has been inconsistent in regard to the effectiveness of resveratrol. And resveratrol is functionally antagonistic with one of the forms of B3, niacinamide, that you might use to raise NAD+.

Since bioavailability of resveratrol is quite low, one variable in its effectiveness may be the delivery system. Dr. Sinclair takes his resveratrol with a small amount of full-fat yogurt in the morning to assist with assimilation since resveratrol is fat-soluble.

But perhaps we should not focus so much on resveratrol because oleic acid, the fatty acid that is famously abundant in olive oil, has been identified as SIRT 1 stimulator. And David Sinclair, PhD has stated is 100x as powerful as resveratrol. 

Although SIRT1 is an important sirtuin, SIRT6 is often considered to the most important sirtuin, and turning on SIRT6 in mice, or giving mice extra copies of the SIRT6 gene, gave them better DNA repair, improved their memory, increased exercise endurance, enabled them to stay thin no matter how much they ate, and extended lifespan.

SIRT6 activity can be increased 55x by cyanidins, a type of flavonoid polyphenol found in red berries. The richest sources of cyanidins are (in descending order of cyanidin-richness): elderberry, blackberry, black currant, sweet cherry, and red raspberry. And the cyanidin content of these berries varies dramatically with elderberry having about 50 times as much cyanidin as red raspberry and about 5 times as much cyanidin as blackberry.

In addition to activating sirtuin activity, it's important to avoid sirtuin inhibitors like bisphenols (plasticizers). When sirtuins are inhibited so is the long list sirtuin's beneficial effects at the top of this post.

Despite the promise of slowing aging by raising NAD+ levels, removal of toxicants appears to be more important. Toxicants that accelerate aging (e.g. by inhibiting sirtuins) are called "gerontogens". In a study by Christopher Shade, PhD on 40 people, they reversed aging by 1 year in 3 months and substantially slowed the rate of aging by using strategies that supported the body's excretion of toxicants. On the other hand, raising NAD+ has not been shown to reduce biological age or the rate of aging, although David Sinclair, PhD provided anecdotal evidence in his book Lifespan that suggests that raising NAD+ may in fact reduce biological age.

Optimize DNA Methylation

DNA methylation is a process by which the body silences the expression of genes by attaching methyl groups, which are molecules consisting of a single carbon atom with three hydrogen atoms attached. As described in a previous post, 7 Steps to Slow and Even Reverse Aging, scientists have found that your aging process can be seen in patterns of DNA methylation. These patterns of DNA methylation are like a “clock” that shows you what time it is on the clock of your life, how old you are biologically. 

So scientists have developed what they call “aging clocks” that are based on these patterns of DNA methylation. Tests of DNA methylation based on these aging clocks are now available to consumers to measure biological age.

DNA methylation tests are currently considered one of the best ways to measure your biological age, and your biological age may to be the single greatest influence on your risk of disease. Conversely, disease (and disease processes that have not yet resulted in overt disease) increase unfavorable patterns of DNA methylation that in turn influence your risk of developing disease. 

For example, diabetes is associated with a 6 to 9 year increase in biological age and general dysregulation of DNA methylation, including hypermethylation (suppression) of tumor suppressor genes, antioxidant regulating genes, and an important gene that impacts insulin, PPARGC1A.

Fortunately, research on the aging process has also begun to show that there are things we can do to shift our DNA methylation toward more healthy and youthful patterns. A pilot study showed that specific lifestyle and nutritional practices reduced the biological age of the already-healthy study participants by an average of more than 3 years in 8 weeks! Rather than repeat it here, for more details on that study and how to optimize DNA methylation, see the "Optimize DNA Methylation" section of 7 Steps to Slow and Even Reverse Aging.

Maintain Telomere Length

As described in the previous post, Understand Your Aging Process: The 12 "Hallmarks of Aging", telomeres are the segments of non-coding DNA at the end of strands of DNA that protect the coding portions of DNA from being lost during DNA replication. Once telomeres become too short, cells can no longer divide without losing functional coding DNA. This is considered to be the reason that human cells can typically only divide a finite number of times (the "Hayflick limit"). 

Although telomere length only has a 40% correlation with lifespan compared to the 96% correlation of DNA methylation "aging clocks", it is still important to maintain long telomeres. Telomere attrition leads to the development of senescent "zombie cells" that secrete pro-inflammatory compounds and influence other cells to be like them. 

Two of the biggest influences on telomere length are stress and toxins. So removing toxins, healing trauma, transforming your mindset, and in general reducing your stress in response to life is important for maintaining long telomeres and avoiding premature telomere attrition.

A diet rich in phytonutrients seems to promote longer telomeres. Some supplements have been developed to promote telomere length, such as TA-65, based on an extract of astragalus. It works by activating telomerase, the enzyme that maintains telomere length.

Customize Your Age Reversal Strategies

The Bio-Individual Blueprint system can be used to focus on age reversal and to chart a path that is customized to your bio-individuality. And keep in mind that many age reversal strategies do not work very well, if at all, if you have aging accelerators occuring in your body. Aging accelerators include things like leaky gut, toxicity (e.g. from bisphenols, heavy metals, etc.), hidden infections, mitochondrial dysfunction, oxidative stress, inflammation, autoimmune disease, hormonal dysregulation, and much more.

If you would like to learn more about how we go about removing aging accelerators and proceeding from that into more direct age reversal strategies, download the Bio-Individual Blueprint Roadmap, watch the walkthrough video, and schedule a conversation.