how old are you? You may have already heard that today we talk not only about chronological age, the one that counts how much time has passed since you left the womb, but also about biological age, which measures the body’s rate of wear and tear and may indicate your level of health.
A new field of science, longevity medicine, is based on the ability to calculate biological age. Today, to know if certain treatments prolong life, we would have to wait for the patients to reach the end of their lives and then calculate their life expectancy compared to the average. Such a science is so far-fetched that it is almost impossible to do. Even the American Food and Drug Administration (FDA) does not really have a category for life-prolonging drugs, which are not aimed at treating a specific disease, nor a protocol for testing such drugs.
If we can measure the rate of aging of a young person, we can also find out what the different factors are that affect it, says Prof. Evelyn Yehudit Bischoff, today a researcher at the Shanghai University of Medicine and Public Health and a visiting researcher at Tel Aviv University. As a specialist in geriatrics, she is working today to redefine her field of practice as longevity medicine. And it’s not the same at all, she clarifies.
What will the future of the age meter look like?
“We realized that the most significant interventions in favor of longevity should be done at a very early stage of life,” says Bischoff, who is currently in the process of establishing a longevity research center at Sheba Hospital, with Prof. Tzipi Strauss, who is a doctor of newborns and premature infants. Bischoff believes that this is the department where intervention for longevity begins.
“Longevity medicine is not a prevention,” emphasizes Bishop. “Prevention means identifying a risk, and preventing the risk of developing into a disease. For example, performing a colonoscopy to detect polyps that may develop into cancer. We are very much in favor of course, but longevity medicine means using various biomarkers to identify and prevent even the risk factor before it occurs. This is one level above prevention”.
3 methods for discovering biological age
Hubert Clock
A measuring clock based on our epigenetic patterns, i.e. the mechanism responsible for “turning on” and “turning off” certain genes
Hematological clock
Age prediction based on blood count and blood biochemistry
glycan clock
Measures how sugar molecules surround different proteins in the body
We, who are already alive, may also benefit from the new longevity medicine, but the great leap will probably be made in those who will be born in the future and spend their lives with a biological age meter worn on their arm, next to their sports watch. He could, theoretically, know what his aging rate is every minute. The watch will tell him that meeting a certain person makes him old, will direct him to a leisure activity that actually rejuvenates him and will know to tell him which food shortens his life and which prolongs it. That person will have to decide if it is worth it for him to invest half an hour now in a long and pampering bath if he knows that it will extend his life by fifteen minutes.
The stuff that decides which garden will turn on
Of course, biological age clocks are not yet at this stage, or even close to it. “Actually, today there is no clear agreement on how to measure biological age,” says Dr. Ilya Stambler, PhD in the History of Aging, Chairman of the Veteran Association, the Movement for Longevity and Quality of Life, and a leader together with Miri Polchak, Senior Director, Investor and consultant in the field of health technologies, the Longevity Nation conference that will be held next week at Bar Ilan University.
According to a recent article published in the MIT Technology Review, it is estimated that so far more than 100 different biological age clocks have been offered to the world, each of which measures things slightly differently.
A large part of these clocks is based on epigenetics. In the last decades, it became clear that certain parts of our DNA can be expressed or remain switched off, and what determines this are substances called methyl (Methyl) that dress on the genes.
The methylation patterns of the genome, which determine which gene is turned on and which remains off, apparently affect our lives no less than genetics itself. Part of this pattern was determined during pregnancy, part in early childhood and part throughout life. There is even epigenetic inheritance, that is, events that happened to our parents or grandparents throughout their lives affect the methylation pattern of our genome.
Prof. Steve Horbeth, Professor of Genetics and Biostatistics at the University of California, developed the first and one of the most famous clocks based on methylation patterns.
Inconsistency between age and wear
Horvath himself is an identical twin, and the differences between him and his twin, Marcus, made him curious about epigenetics. Among other things, he was bothered by the question of how he is straight and Marcus is gay. He sought to examine this question in a study he conducted in 2011, in which he looked for epigenetic differences that predict sexual orientation. He didn’t find them, but he did see an unusual relationship between the chronological age of the subjects and their epigenetics.
The more interesting discovery was that the correlation was not perfect. Epigenetics is not a simple time clock, which is what gave Hobarth the idea that it might be counting time differently, according to the wear and tear of the body. He built an algorithm known today as the “Hubert Clock”, with which he can predict a person’s age, based on 353 methylation markers in the genome. But of course that’s not the point. We know how old we are. The question is whether methylation can actually predict who will die or age before their chronological time.
Indeed, Huberth has shown in several published papers that he can predict lifespan from methylation patterns. He also showed that these patterns indicate “biological aging” in people with AIDS, Alzheimer’s, Parkinson’s, people with obesity and people with Down syndrome. He also found that “biologically older” people have difficulty on average with cognitive and physical tasks, more than people of their chronological age but “biologically young”.
Other studies have shown that removing the ovaries at a relatively young age, before the official onset of menopause, is associated with a jump in biological age as measured by the methylation clock.
And what slows down the clock? No big surprises for now. Higher education, a vegetarian diet or one based on plants and lean meat, physical activity and the reduction in alcohol consumption – all these have a positive effect on the rhythm of the clock. Men epigenetically age a little faster, and indeed their lifespan is shorter on average. Hispanics in the US age epigenetically more slowly, which could perhaps explain the “Hispanic paradox”, the imperfect relationship between the lifestyle and public health challenges of this sector, compared to their life expectancy.
A statistic that is perhaps more surprising is that descendants of people who lived to a very old age (105 and over) usually have a lower biological age on average.
It was also found that the methylation clocks “tick” at a higher rate during childhood and adolescence, when the body develops, and slow down when reaching adulthood.
A perfect remote clock
Today there are already several commercial companies that offer to check the biological age using epigenetics, based on a saliva, blood or urine test. One of the companies even offers, for a paltry sum of $200, to check the age of your dog, based on Hobarth’s DNA clock.
It is not certain that the results will be accurate, since it is already clear that the methylation patterns tell only part of the story. For example, if we predict the age at which a certain person will die using Huberth’s clock, and then add another detail to the information – whether that person smoked or not – we significantly improve the clock’s ability to predict the age of death.
Ostensibly, we would expect the information about smoking to be “priced” in the methylation patterns, if these indeed measure the rate of wear and tear of the body, but it turns out that the clock does not take into account all the risk factors.
Furthermore, it turned out that the methylation clocks underpredict biological age as people get older. Does this mean that those who have already reached old age survived because they had a young biological age, or maybe the things that happen to us in old age, the ones that eventually kill us, are not reflected in the methylation clock?
These questions raise a more fundamental question: Is metallization the clock of biological age in the world, or is it one risk factor among many. And if it is one risk factor, to which aging process is it related? These issues are now at the forefront of research.
Young organ, old organ: not all tissues are alike
Measuring biological age gets even more complicated when you take into account that different tissues in our body are characterized by different methylation patterns. Huberth actually made an effort to show that there is a correlation in the biological age of the same person in different tissues, meaning that if you are young on the ring finger of your right hand, you probably won’t be very old on your left toe. But there are also surprises.
For example, breasts are beards. The biological age measured in the breast will usually be higher than the biological age measured in the blood of the same woman. And in women who have had breast cancer, breast tissue that is adjacent to where the cancerous tumor was, is usually even “older”. This does not happen, for some reason, in other cancers that have been tested.
This study led to another study, in which it was found that the blood of women who had breast cancer showed signs of “biological aging” according to methylation clocks, even before the disease was diagnosed. However, this measure is not specific or accurate enough to provide a diagnosis.
Cancer tissue itself is confusing. Cancer tissues with certain genetic characteristics appear chronologically younger than the same person’s healthy tissues, while cancers with other genetic characteristics appear older. These are evidences that different types of cancer are more different diseases than we might think today, but they don’t say much about aging.
Brains, fortunately for us, age slowly, and especially in old age their aging slows down.
Blood test is the next watch?
Simultaneously with the development of biological age clocks based on epigenetics, additional measurement methods were developed. One of them is the length of the telomeres – the parts of the genome that get shorter as we age. A correlation was found between the health and function of cells, including human cells, and the length of the telomeres in that cell.
An entrepreneur named Liz Parrish, who founded a company called BioViva that deals in the field of life extension, even underwent a treatment to lengthen her telomeres in 2015, according to her testimony. This treatment is illegal in the US, where she lives, so she underwent it in Colombia. Frish claims that her biological age, which was 66 before the treatment, dropped to 44 as a result, coincidentally also her chronological age at the time. In 2020, she underwent the The treatment again, and she claimed that her biological age dropped below 25.
However, in the laboratory no such clear connection was found between telomeres and biological age, as measured by the Huberth clock. When cells undergo telomere lengthening processes in the laboratory, they continue to mature epigenetically. That is, it seems that these are processes that are not completely coordinated. It is difficult today to say whether both are part of the same general mechanism of aging. If there are indeed two mechanisms of aging here, then there are also two challenges – or two opportunities – to slow down the process.
Another “hot” clock is the hematological clock. A study published in 2018 in the journal Journals of Gerontology – Series A showed that age can also be predicted based on blood counts and blood biochemistry, if they are passed through an artificial intelligence algorithm. The researchers entered numerous parameters into their biological age clock, but identified that five measures in the blood were most highly correlated with age: albumin, a protein commonly associated with kidney and liver function; sugar, a measure that most of us know and is linked to diabetes and the metabolic syndrome; Urine (urea) is also related to kidney function; The amount of red blood cells, and ALP (alkaline phosphatase), a substance that is also linked to liver and bone function.
“Until today, the methylation clocks best represent the real age,” says the group of researchers led by Dr. Polina from Moshina, today a senior information analyst at McKinsey and at the time of writing the article a doctoral student at the University of Oxford. “But the epigenetic state of a certain person is relatively stable, so these clocks Low effectiveness in measuring the effect of various interventions in the aging process.” The hematological age, as it may be called, may be a better measure of the effect of changes.
Several groups of researchers are working on hematological clocks around the world. This is an attractive study due to the relative ease of obtaining the information, even regarding people who have already died of old age, and therefore their final life expectancy is known.
Another measure is glycans, sugar molecules that surround various proteins that work in our body. The way the proteins are “sugared” affects their function, and there is already a commercial company that offers to measure the pattern of glycation to tell you how fast you are aging, although this clock, like the others, is not yet validated by the medical world.
Other groups of researchers are engaged in the development of biological age clocks based on images of the facial skin, markers from sports watches, and artificial intelligence analyzes of long and detailed lifestyle questionnaires.
The goal: a drug to slow down aging
Huberth himself does not exactly adhere to the metallization clock that made him famous. These days he is trying to develop a variety of watches, including hematological watches and lifestyle based watches, as well as trying to combine all these watches together.
The latest scientific word in the field is “dismantling” the clocks of aging. Research led by Dr. Morgan Levin, formerly a lecturer at Yale University, sought to track specific indicators of epigenetics to understand how each of them affects aging. According to this approach, epigenetic aging is also not one process, but a collection of many processes. The group identified Two epigenetic pathways among hundreds that have been tested, which can be sensitive to external intervention, for example through drugs.
The goal is ultimately to make any biological age clock or part of it an acceptable measure by the FDA, in order to develop drugs to slow down aging. If and when that happens, longevity medicine will likely become a thriving medical field.
In the meantime, Levin left her academic position in favor of a leading position at Altos Labs, an aging research laboratory located at the seam between the academic and commercial worlds. The company raised $3 billion, among others from Amazon founder Jeff Bezos and Russian-Israeli entrepreneur Yuri Milner, and this despite the fact that it still has no horizon for a commercial product. It seems that for the company’s investors and researchers, the biological clock is ticking too fast for academia.