Measure and lower biological age

For thousands of years, people have pursued the desire of eternal youth. Over the years, people have tried not only strange but also sometimes life-threatening methods. Whether mercury treatment, electron therapy, or the implantation of monkey glands - there were no limits to creativity in the past. X-ray facial treatments were also in vogue for a while. Fortunately, thanks to modern research, we know much more today. Whereas in the past, aging was only determined by visual characteristics or one's own feelings, there are now scientific methods such as the Horvath clock that can objectively determine biological age.

But not only that, science has shown that our biological age is reversible. Some even dream that in the future we will be able to turn back our biological clock completely and thus (theoretically) live forever. Even though we are still a long way from that today, research in the field is developing rapidly.

Here we give you an overview of this exciting field. We explain what distinguishes biological age from chronological age, what the Horvath clock is, and why research into human cloning has triggered a potentially revolutionary future therapy.

What do we mean by aging?

Before we get into the heart of the matter, we must first deal with aging per se. Because even according to current knowledge, the process of human aging is not yet fully understood. What is behind the aging process? Why are we so much more susceptible to disease in our later decades of life?

According to recent research, genetic and epigenetic factors in particular are crucial to the aging process in humans. To understand the complex mechanisms behind aging, scientists such as López-Otin have defined the Hallmarks of Aging. They are the key mechanisms that contribute to aging. You can learn more about them here.

What is biological age?

Biological age is not only measured by the months or years a person lives (this is chronological age), but refers to physical and mental condition. Specifically, this means that a person is 40 calendar years old, but their biological age can be less than or greater than 40. The more the biological age differs from the chronological age, the younger or older you are at the cellular level. A baby is born with a biological age of 0 years. However, as time passes, the biological age of each person increases.

Some people manage to "keep themselves looking good" colloquially. In other words, this expression describes that their appearance seems younger than the actual chronological age. Likewise, there is the opposite case, where people look significantly older or sicker than they actually are.

Did you know. At the so-called Rejuvenation Olympics, a kind of competition for rejuvenation, there is an "Epigenetic Leaderboard". There, participants compete to see who can lower their biological age the most. The founder is Bryan Johnson, a biotech entrepreneur who invests several million dollars a year in rejuvenation therapies. There is no German equivalent (yet). Here you can learn more about the rejuvenation routine from the well-known tech CEO.

What role does biological age play in longevity?

Biological age is directly related to a person's longevity. This large meta-study demonstrated that measuring biological age is a reliable method for expected lifespan. In addition, the researchers identified factors that accelerate biological age. These included many chronic diseases, such as diabetes mellitus, cardiovascular disease, HIV but also smoking, drinking and socioeconomic status. However, if there are factors that cause people to age faster, it must be possible to "turn back the clock" or at least slow it down.

Doctors such as Oliver Zolman, founder of the Longevity School and Zolman Clinics, are working on this. With his approach, he wants to turn the biological clock of 80-year-olds back to that of a 60-year-old by 2030. Sounds ambitious, but also a bit surreal at first. But there will certainly be significant breakthroughs in the field of longevity research in the coming years - and all of them are directly related to biological age.

Measuring biological age thanks to Steve Horvath

Especially in the context of the aging process, there are several clues that can be used to evaluate biological age, among other things. These include the determination of telomere length or the evaluation of certain biomarkers in the blood. Probably the best-known method currently available for determining biological age is a so-called "epigenetic test". The idea for the Horvarth Clock, which was presented in 2011, can be traced back to the relatively new research field of epigenetics.

Epigenetic changes do not affect the genetic code itself. This is what the ancient Greek syllable "epi" means, meaning around or on - i.e. beyond our DNA. Epigenetics is therefore not concerned with mutations, but with modifications that influence the activity of certain genes. One of these modifications is methylation, which leads to the shutdown of cellular processes. In this process, a chemical group (CH3) is transferred to certain parts of the genetic code, which means that proteins, for example, are no longer produced.

With increasing age, not only random but also typical epigenetic changes occur. Since these changes (methylations) can be measured, it is possible to draw conclusions about a person's biological age. From this information, Steve Horvath and his colleagues have been able to develop a special algorithm that can be used to determine biological age.

epiAge Test from MoleQlar

A team led by Professor Moshe Szyf at McGill University in Montreal refined Horvath's methodology. Using artificial intelligence, as well as machine learning, the information gathered can be analyzed more quickly and put into a broader context to identify underlying patterns and changes and derive important insights. The MoleQlar epiAge Test is based on exactly this method. By analyzing a certain number of markers, the most accurate and, above all, reproducible results are possible.

Comparison tests often analyze hundreds or even thousands of markers - but it is now known that this is not an advantage. The tests promise multiple data points - but the complexity makes for big differences when a test is run twice.

Biological age - can it be more understandable?

Granted, that whole thing was pretty scientifically phrased. Here's an analogy that might help you better understand an epigenetic age test. Imagine that your DNA is the text in a book. But you never read the whole book, because it's way too big, you always read sections of it. And to help you remember which sections you want to read, you put little Post-It notes at the beginning and end of the text passage. These Post-it notes are your epigenetic markers, methylated spots on your DNA. They do not change your DNA per se, but determine which sections are read or found and which are not.

Through researchers like Dr. Steve Horvath, we have found that some of these "post-it notes" lend themselves to measuring a person's biological age.

Why should I lower my biological age?

A high biological age is associated with many diseases such as cancers, cardiovascular diseases and neurodegenerative diseases such as dementia. Researchers have developed algorithms that allow them to statistically evaluate the influence of biological age.

In addition to the epigenetic clock, telomere length has also become the focus of longevity research. One study showed that telomere length is inversely associated with cardiovascular disease. This means that the longer the telomeres, the lower the probability of suffering from cardiovascular diseases. A similar relationship has been found between telomere length and Alzheimer's disease. It therefore makes perfect sense to keep one's biological age as short as possible.

Did you know? In a clinical study conducted by Prof. Sekhar, an improvement in various Hallmarks of Aging was observed in elderly subjects taking GlyNAC on a regular basis. These included less inflammation, fewer senescent cells, reduced genomic instability, and improved insulin sensitivity. This is one of the few studies where direct results have been examined in humans and not just animals. If you want to know more about the exciting molecule GlyNAC and its mode of action, you can find here the article.

How can I lower my biological age?

There are a variety of methods and strategies to lower biological age. Some of them are based on the abandonment of certain habits or a change in lifestyle. Oliver Zolman has also compiled scientific figures on this.

According to experts, being a non-smoker compared to smoking, can extend life by up to 12 years. Sports and exercise would potentially extend life by 8 years. Other measures include a calorie-reduced diet (Read more here), a healthy BMI between 18.5 and 22.5 and, paradoxically, according to one study, the consumption of half a glass of wine due to the polyphenols it contains.

One of the potentially interesting ingredients in (red) wine is the so-called resveratrol (here you can read more about it). It should be mentioned here, however, that the correlation between longevity and moderate wine consumption was not always reproducible in follow-up studies.

Rejuvenation á la Bryan Johnson

Bryan Johnson, the biotech entrepreneur and longevity hacker mentioned earlier, also relies on a sophisticated longevity plan to lower his biological age. To do this, he eats 3 vegan meals and fasts between 16 and 18 hours a day. We also wrote about the benefits of a plant-based diet and interval fasting in a past post.

Johnson's diet consists of larger amounts of fiber-rich fruits and vegetables and plant-based protein. In addition, he takes the mind-boggling amount of 111 supplements daily! His daily supplement routine includes vitamin D, omega-3 fatty acids, NAD precursors, calcium alphaketoglutarate or glucosamine. If you want to learn even more about Bryan Johnson's sometimes bizarre routines, check out our article about his project Blueprint.

Did you know? Blood for rejuvenation - this questionable method was tested on mice by scientists at Harvard and Duke University. In the process, the blood circuits of young mice were combined with those of older mice - also known as parabiosis in technical jargon. It was shown for the first time that in addition to improved stem cell function, increased cognitive performance, the epigenetic age of the old mice could also be lowered. This led to a longer life of the old mice and to a better state of health. The task of the research is now to find out which factors in the blood of the young mice are responsible for the decrease in biological age.

NAD boosters, SIRT1 activators and spermidine - how longevity molecules affect aging.

In a very comprehensive paper, noted aging researcher Dr. David Sinclair described the molecular processes behind aging and gave a summary of studies on the reversal of epigenetic aging. In doing so, he describes four stages in the life of a cell:

• A0: The embryonic cell. At this age the cell is young and healthy
• A1: The young cell: the first age changes occur in the otherwise healthy cell
• A2: Aged cell: the cell has aged and is no longer as functional
• A3: Senescent cell: the cell has reached the end of its life and can no longer divide

In his paper, Dr. Sinclair describes possible starting points for reversing biological age. The main focus is on A2 cells, which can be rejuvenated in various ways. The whole thing has to do with the fasting process. We have briefly summarized the most important findings for you below. If you want to know the exact biochemical background, you can find it in our fasting article.

Sirtuins

Sirtuins are a group of proteins that are potentially life-prolonging. In particular, SIRT1, which requires NAD as a cofactor, plays an important role. High levels of NAD, for example, through precursor supplementation, together with activation of SIRT1 (for example, through fasting, or molecules such as resveratrol or glucosamine) lead to a measurable reduction in biological age.

Spermidine

In addition, the molecule spermidine also appears to be effective. On the one hand, spermidine is closely related to improved autophagy. If our in-house garbage disposal system is strengthened, old, broken cells (A2) are better disposed of. At the same time, spermidine acts on histones. You can think of histones like the wrapping string of a gift. They are located around your DNA. Spermidine, like SIRT1, can loosen histones so that the DNA underneath can be read. The key here is that the loosened histones are located at sites on the DNA that are associated with longer life.

Did you know? As we age, our NAD levels decrease. We now know that high NAD levels have a positive effect on our health. They can also help lower our biological age by supporting the activity of SIRT1.

How can we counteract the decrease in NAD levels with age? There are three possible approaches to this: First, we can supplement the precursors of NAD. Second, support the NAD-producing enzymes. And third, slow down the degradation of NAD. All three possibilities combined you can find for example in regeNAD Complex from MoleQlar. If you would like to determine your NAD level, then our NAD dry blood test offers you an easy way to do so.

Reprogramming old cells? A possible approach for the future

Strengthening old cells through exercise, supplementation and diet is a promising approach in aging research. But if we want to turn back the biological clock even further, this approach will not be enough. This is where we need to dive into the research field of stem cells:

What are stem cells anyway?

Each of us has a whole arsenal of stem cells. For example, stem cells in our bone marrow ensure that we can constantly produce new red blood cells, immune cells and platelets. Put simply, a stem cell is capable of developing into different cells. Their "potency" depends on the type of stem cell.

Let us return to our example: A "hematopoietic" stem cell in the bone marrow can transform into a red blood cell, an erythrocyte, during division - but also into a lymphocyte or monocyte. Both are representatives of our immune system. However, the hematopoietic stem cell cannot transform into a kidney, liver or heart muscle cell. As our stem cells become less efficient with age, we have fewer immune cells and are more susceptible to infections.

So perhaps the secret to biological rejuvenation is hiding here? Could we use healthy, new stem cells to renew our organs, strengthen the immune system and stop aging? This is still a vision of the future, but it could well become reality.

Stem cells and the Yamanaka factors

The basis for this was laid by the Japanese Nobel Prize winner Shinya Yamanaka from Kyoto University. He discovered the Yamanaka factors in 2006/2007. By introducing 4 genes, Yamanaka was able to convert skin cells back into embryonic stem cells. These are also known as induced pluripotent stem cells, or iPS for short. These cells are capable of transforming into all types of tissue, similar to a human clone.

However, the discovery was followed by disillusionment, because the introduced genes triggered cancer. So we are not yet ready to use stem cells to renew our organs. However, research in this area is being carried out with great zeal, and it is possible that groundbreaking new therapeutic approaches could emerge.

Summary

Biological age is a decisive factor when it comes to longevity. Therefore, you should try to keep it as low as possible. According to the motto "Healthy Ageing", which means nothing other than that you age healthily or that your chronological age is higher than your biological age. In the future, it will be exciting to see if and when there will be rejuvenation therapies that can drastically reset biological age. In MoleQlar Magazine we will keep you up to date!