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Anti-ageing and the Horvath clock - How old am I really?
Longevity Magazin

Anti-ageing and the Horvath clock - How old am I really?

Imagine having a watch with which you can measure the age of almost every cell in your body with astounding accuracy. What sounds like an invention from the future is already possible today. We have a mathematician, the German-American researcher Steve Horvath, to thank for this. With the Horvath clock named after him, we can determine the biological age of cells to the nearest month.

In this article, we dive deep into the world of the Horvath Clock and explain what makes this epigenetic clock so unique, how it works, and what implications it has for ageing research. You will also learn more about its discoverer, Steve Horvath.

Who is Steve Horvath?

Steve Horvath is a German-American biostatistician, geneticist and leading researcher in the field of ageing research. Born in Germany and later immigrated to the United States, Horvath currently teaches as Professor of Human Genetics and Biostatistics at the University of California, Los Angeles (UCLA).

Even in his early youth, Steve Horvath was fascinated by the concept of ageing. The young Steve Horvath was particularly interested in the question of how to live longer in good health. Together with his twin brother and a mutual friend, the three vowed to spend their professional lives striving to answer the question of healthy ageing. The model was the ancient Babylonian epic of Gilgamesh, who dives into the depths of the ocean in search of eternal youth to find the herb of immortality.

Steve Horvath did not discover "the herb of immortality", but he developed a mathematical model with which he was able to depict ageing itself. And this, he hopes, will create the basis for reversing ageing too.

What is the Horvath Clock (epigenetic clock)?

The Horvath Clock is an epigenetic test that measures thebiological age of an individual. This method is based on the analysis of DNA methylation patterns, which are systematically altered over time. DNA methylation is an epigenetic mechanism in which methyl groups are added to the DNA molecules and thus gene expression is influenced without changing the DNA sequence.

Steve Horvath discovered that certain regions of DNA - so-called CpG sites - show systematic changes in their methylation patterns over the course of life. By studying and mapping these specific changes, Horvath was able to create an "epigenetic clock" that accurately predicts the biological age of an organism based on methylation at 353 specific CpG sites.

Wusstest Du?

The scientific work of Steve Horvath was initially rejected by many editors. The results and accuracy of the Horvath clock were " too accurate to be true." After several rejections, Steve Horvath first treated himself to three bottles of beer and then wrote an angry letter to the editor. With success, his article was subsequently published in the renowned "Genome Biology".

Measuring biological age with the Horvath clock

Traditionally, a person's age is defined by chronological age, i.e. the number of years since birth. Biological age, on the other hand, refers to the physiological state of the body and can differ greatly from chronological age. A younger biological age may indicate better health and a longer life , while an older biological age may indicate an increased risk of age-related diseases and premature mortality.

The Horvath Clock provides a method for assessing this biological age by analyzing the pattern of DNA methylation in blood samples, saliva or other cell types. This methodology has proven to be extremely accurate and provides valuable insights into the ageing process at the cellular level.

Wusstest Du?

Biological age is incredibly accurate, even by scientific standards. Biomarkers have a correlation of approximately 0.6 to 0.7. For comparison, the length of telomeres, for which Elisabeth Blackburn received the Nobel Prize, had a correlation with age of 0.5. The Horvath Clock had a correlation of an impressive 0.96!

Or to put it another way, the Horvath Clock is a very accurate measuring instrument.

The basis of the Horvath Clock: epigenetics and DNA methylation

Epigeneticsis a field of research concerned with the changes in gene expression that occur independently of changes in DNA sequence. Epigenetic mechanisms, such as DNA methylation, play a key role in the regulation of many biological processes and are crucial for an organism's ability to adapt to environmental factors.

The Horvath Clock uses these epigenetic principles to estimate biological age. By systematically detecting the methylation states of 353 specific CpG sites, the clock can make precise predictions about the biological age of the tested tissue . These CpG sites were identified based on their strong correlation with chronological age in different tissue types, making the Horvath Clock a universal tool for various biological samples.

Methylation, epigenetics - can it be simpler?

Admittedly, many of the concepts mentioned are highly scientific. However, to help you get a better understanding of them and avoid having to read dozens of studies, we will try to explain them to you more easily using an example.

Imagine your DNA like an oversized orchestra.Around each instrument are volume controls that can be turned up or down. These volume controls symbolize epigenetics. Through various biochemical processes (such as the aforementioned methylation), our body can make certain areas of DNA louder or quieter. Translated, this means that epigenetics determines which parts of the DNA are read and which are not.

Steve Horvath has now discovered that there are very specific patterns in the setting of these volume controls for ageing.And this is exactly what the Horvath clock measures. Horvath can therefore say quite precisely how "old" a cell is on a biochemical level.

Applications of the Horvath Clock in research & medicine

The Horvath Clock has a wide range of applications, both in basic research and in clinical and medical contexts:

  • Research on ageing and longevity: The Horvath Clock enables scientists to investigate the influence of various factors on the ageing process. These include environmental factors, genetic predispositions and lifestyle changes. Research results can be used to develop strategies to promote health and prolong life.
  • Early detection of diseases : Biological age, measured with the Horvath Clock, can provide early indicators of age-related diseases such as cardiovascular diseases, cancer or neurodegenerative diseases. This enables early interventions and targeted preventive measures.
  • Monitoring of therapies : The Horvath Clock can be used to evaluate the success of anti-aging therapies or other medical interventions. Changes in biological age could indicate how effective a particular treatment is.
  • Clinical trials : In clinical trials, the Horvath Clock can be used to assess the effects of new drugs or interventions on the ageing process, identifying their potential benefits or risks prior to market launch.

Horvath Clock, Molecular Profile, DunedinPACE or TruAge - what's behind the new generations

In addition to the Horvath clock, there is now a whole range of epigenetic teststhat can measure biological age. The concept is still largely the same, i.e. the newer tests also measure methylation sites on the DNA. Tests such as the DunedinPACE test indicate the rate at which you age. In case you're wondering where the name comes from. Dunedin is a city in New Zealand where the data for the test was collected. The DunedinPace and the TruAge test are also the basis of theRejunvenation Olympics. A competition created by the American Bryan Johnson to determine who ages the slowest. In addition to Bryan Johnson, this has also attracted other biohackers,z.B . 61-year-old Dave Pascoe, who has a biological age of just 38. Pretty impressive.

What influences the Horvath Clock?

The Horvath Clock and its successors have been tested for more than 10 years. Some interesting facts emerged. The most astonishing one is probably that biological age can be influenced. The biohacker scene in particular was able to prove impressively that you can turn your biological age backwards.

But what about the other direction and are there also cases in which the biological age only changes for a short time?

Older biological age - a risk marker?

There is still no consensus in the scientific community on how to interpret the results of the Horvath clock. Are they "just" a mathematical model or do they really reflect ageing processes in our bodies? In order to clarify this question a little better, researchers have analyzed huge amounts of data. One correlation emerged quite clearly. People with a high discrepancy between chronological age and biological age have an increased risk of developing certain diseases z.B. of the cardiovascular system.

OP, stress and infections as short-term influencing factors

Imagine you have taken a test to determine your biological age and you are older than expected. This is certainly a shock for many people and also raises the question of whether you now have an increased risk of certain diseases. This example makes it clear that the measurement of biological age does not always show the complete picture. This is because it can also be influenced by short-term events.

In order to prove this effect, the researchers took a closer look at various scenarios in a study:

Surgeries make us older - at least in the short term

Surgeries mean a lot of stress for our bodies. It was therefore reasonable to assume that this affects our biological age. And indeed. Shortly after an operation, our biological age shot up. This is probably a sign that our body is using a lot of resources for repair. The good news. Just a few days after an operation, the biological age normalized.

Infections influence the Horvath clock

Infections, such as COVID-19, also have a demonstrable effect on our biological age. They make us appear older than we actually are for a short time. For this reason, it is not recommended to take an epigenetic age test if you feel ill or if you have just had an infection. This can falsify the results.

And the researchers found one last, exciting point in their work. Stress not only seems to make us older on the outside, but stress also influences our biological age on the inside.

Case studies: Practical applications of the Horvath Clock

In recent years, the Horvath clock has established itself as a fixed instrument in science. We now know that biological age can provide us with very sound information about our health. The right nutrition , exercise and stress reduction can reduce biological age.

The Horvath clock and its successors can also be used to test potential molecules in longevity research. For example, in one study the molecule alphaketoglutarate was tested for 7 months. The test subjects took a daily mix of alphaketoglutarate and vitamins for this period.The impressive end result: the participants were able to reduce their biological age by an average of 8 years!

Challenges and future research

Despite the impressive success of the Horvath Clock, there are still challenges and unanswered questions. One of the biggest challenges is to better understand the mechanisms underlying the epigenetic changes measured by the Horvath Clock. A deeper understanding could help to develop targeted interventions that could slow or reverse the ageing process.

In addition, it is important to conduct further validation studies to verify the accuracy of the Horvath Clock in different populations and under different environmental conditions. Such studies could help to confirm the general applicability of the clock and identify possible limitations.

Conclusion: The revolution in ageing research

The Horvath Clock and Steve Horvath's research have revolutionized our understanding of aging. By precisely measuring biological age using DNA methylation markers, the Horvath Clock provides valuable insights that go far beyond what is possible using conventional measures of chronological age. These findings have the potential to improve the prevention and treatment of age-related diseases and to develop strategies to promote healthy ageing and an extended lifespan.

Steve Horvath's work impressively demonstrates how interdisciplinary research and innovative thinking can lead to groundbreaking discoveries. The Horvath Clock is a prime example of how epigenetic research can find practical applications in everyday life and offer everyone the prospect of a better quality of life.

This article was created by the MOLEQLAR editorial team and follows our editorial guidelines.

Sources

  • Demidenko, Oleksandr et al. “Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test.” Aging vol. 13,22 (2021): 24485-24499.
  • Gibbs WW. Epigenetic clock: accurate to within a few months. Spectrum of Science. (2014)
  • Horvath, Steve. “DNA methylation age of human tissues and cell types.” Genome biology vol. 14,10 (2013): R115
  • Levine, Morgan E et al. “An epigenetic biomarker of aging for lifespan and healthspan.” Aging vol. 10,4 (2018): 573-591.
  • Lu, Yuancheng et al. “Reprogramming to recover youthful epigenetic information and restore vision.” Nature vol. 588,7836 (2020): 124-129.
  • Moqri, Mahdi et al. “Validation of biomarkers of aging.” Nature medicine vol. 30,2 (2024): 360-372.
  • Poganik, Jesse R et al. “Biological age is increased by stress and restored upon recovery.” Cell metabolism vol. 35,5 (2023): 807-820.e5.

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