Hacking aging - Part 2 — Evolve Further

This is the second part of the series on anti-aging. In this article we will examine some promising approaches to hacking aging, backed by scientific research, including fasting and various supplements.

Fasting

What is fasting and does it work?

Fasting is going without food, or consuming a calorie restricted diet for an extended period of time, some fasts are as short as 16 hours, some can be months long.

Fasting is probably one of the most extensively researched and evidence backed approaches for longevity. Strong evidence exists that restricting calories increases lifespan in mice and humans.

Fasting need not be constant, instead fasting for periods of time at regular intervals is sufficient to generate the same benefits seen in long term fasting studies. Interestingly rather than going without food completely similar results to fasting were observed using a Fasting Mimicking Diet (FMD), that is a diet low in calories, sugars, and proteins but high in unsaturated fats (1), one such popular diet is the Keto diet.

How does it work?

When fasting the body no longer has enough carbohydrates to sustain it and therefore switches to autophagy for its energy source. Autophagy literally translated from greek means “to eat oneself”.

The body feeds on the various damaged parts of cells such as cell membranes and proteins, thereby removing them from the body. When these sub-cellular parts are removed they are replaced with new parts, thereby restoring the cells to proper function.

In addition to promoting autophagy fasting also promotes the production of growth hormone, which helps the body produce these new replacement parts (2).

What are the benefits?

One study compared people who consumed a fasting mimicking diet for 5 days once a month for 3 months to those following a regular diet. Those who followed the periodic fasting diet showed reduced body weight and fat, lower blood pressure, and decreased IGF-1 hormone. IGF-1 has been linked to aging and disease. Further studies showed the fasting diet also decreased cholesterol and markers for inflammation (3). Animal studies have demonstrated a range of benefits including wound healing (4), and brain function (5).

How can I implement fasting in my daily life?

There are a number of ways to fast, some common approaches include:

16:8 fast: This involves limiting consumption to an 8 hour window per day. This cycle can be practiced as often as you like, once, twice per week or every day. An example of this would be skipping breakfast, but having a healthy lunch and dinner.

24 hour fast: This involves skipping meals for 24 hours, e.g. if your last meal is dinner you do not eat again until dinner the following night. This type of fast is more difficult and therefore not practiced as often, some people choose to do this once a week or once a month.

5:2 fast: This involves eating regularly for 5 days a week and eating a calorie restricted diet (no more than 500 calories per day) for 2 days a week.

Similar results can be achieved by following a calorie restricted diet such as the Keto diet. More information on the Keto diet can be found here.

Calorie Restriction Mimetics (CRM)

Let’s face it, fasting sucks, it is difficult for most people to maintain a fasted state, or even maintain intermittent fasting over a long period, therefore scientists have been researching Calorie Restriction Mimetics (CRM’s).

CRM’s are compounds when ingested mimic the body’s response to being in a fasted state. One promising group of CRM’s are sirtuin activators.

What sirtuans and sirtuan activators?

Sirtuans are proteins in the body which are responsible for DNA maintenance and repair. These genes are activated when the body senses it is in a stressed state (e.g. fasting). One of the seven sirtuans found in humans, SIRT1, can be activated by natural compounds known as polyphenols. Polyphenols are found in plants, where they are involved in defending plants from ultraviolet radiation and pathogens. Polyphenols include pterostilbene which is found in blueberries, resveratrol which is found in the skin of grapes and curcumin.

What else is required for sirtuan activators to work?

Sirtuans can only function in the presence of nicotinamide adenine dinucleotide (NAD+), NAD+ is a coenzyme found in all cells, it is responsible for helping turn nutrients into energy and regulating other biological activity. NAD+ levels in humans decline with age. Therefore boosting levels of NAD+ can help Sirtuans to continue functioning into old age.

Do these supplements work and can they by purchased?

Recent studies have highlighted potential positive effects from increased NAD+. One study showed that mice supplemented with NAD+ precursers showed increased levels of DNA repair and the tissues of 2 year old mice appeared identical to that of 3 month old mice (6). Another study showed increased levels of cognitive ability (7). There are not yet any results from human trials.

NAD+ can be taken directly or NAD+ levels can be increased by supplementation with the NAD+ precursors Nicotinamide Riboside (NR) or Nicotinamide Mononucleotide (NMN), both have been shown to raise the levels of NAD+ in the body. NR and NMN are derived from nicacin which is a form of vitamin B3, an essential human nutrient.

Most of these supplements can be purchased online, but beware are a lot of inferior products, and many which are not what the claim to be. Make sure you go with a reputable brand.

Senolytics

What are senescent cells?

As we age the body accumulates an increasing number of senescent cells. Sensescent cells are cells which are not functioning properly, but have not yet died off and been recycled, as cells are when we are younger.

Senescent cells secrete inflammatory factors, and appear to play a role an important role in ageing and many age related diseases including dementia, diabetes and cardiovascular disease (8).

Do senolytics work, and where can I purchase them?

The class of drugs known as senolytics target senescent cells, removing them but leaving healthy cells untouched. In various mice studies it has been shown that removal of senescent cells can prevent or delay tissue dysfunction and extend healthy lifespan (9, 10).

Many plant based compounds have powerful senolytic effects, one study compared the senolytic efficacy of various plant compounds in mouse cells and in senescent human fibroblasts, the results can be seen in the chart below (11).

Mouse embryonic fibroblasts (MEFs) were treated with a panel of flavonoid compounds, and the the viability of senescent cells and total cells were measured.

Among the 10 flavonoids tested Fisetin was the most effective. Fisetin is a natural compound found in strawberries, apples, cucumbers, grapes and onions. There are only a very few suppliers online, more common is curcumin, which can easily be purchased, fresh or in pill form. The bioavailabiliy of pure curcumin is relatively low, however taking it with piperine has been shown to increase its bioavailablity by as much as 2000%.

Metformin

No longevity discussion would be complete without mentioning Metformin. Metformin is a drug used to treat diabetes. When administered it mimics caloric restriction and therefore has also been shown to extend lifespan. The exact mechanism by which metformin works to increase lifespan is not yet fully understood. It appears to operate on a number of pathways including decreasing IGF-1, inhibition of mTOR, reducing DNA damage, and influencing inflammation and autophagy and influencing digestion in the gut microbiome (12).

Studies have demonstrated Metformin’s ability to increase lifespan in mice (13, 14). Several studies have shown metformin may be beneficial for decreasing the incidence of cancer, improving cognitive function and increasing lifespan (15, 16, 17). More targeted studies in humans are currently being conducted.

Metformin can in most countries be purchased with a doctor’s prescription.

Stacking for increased benefits

Evolve Fitness recommends stacking a sirtuan activator (e.g. resveratrol) an NAD+ precurser (such as NMN or NR) and a senolytic (curcumin), these can safely be taken on a daily basis however we recommend periodically taking a break from all supplement regimes. If you are considering taking metformin for longevity purposes we recommend you speak with your doctor first.