Five precautions to prevent ageing
6 апр. 2022 г.
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Dr. Ayşegül Çoruhlu


As we enter each new year, we promise ourselves to strive to be healthier. In this article, I will give you some suggestions that will help you stay healthy with small habit changes you can make in 2022. I will give you tips on keeping your biological age younger than your calendar age.
First, let’s find out what makes us age fast. Then let’s make suggestions to correct these negative conditions. What are the cellular causes that age us fast?
Cellular oxygen deficiency
Oxygen must be able to reach each cell sufficiently and the cell must be able to use this oxygen correctly. What could be the reasons why oxygen cannot reach the cell sufficiently?
Smoking
When cigarettes are inhaled, apart from the negative effects of harmful chemicals on health, the lack of oxygen caused by cigarettes is our main concern. Breathing cigarette smoke instead of getting oxygen with each breath reduces the oxygen going to the cells. This creates an entire hypoxia, that is, a lack of oxygen, not just the lungs. You only associate smoking with lung cancer or heart disease, but the picture is bigger. Less oxygen in the breath reduces the oxygen in the microcirculation throughout the body. When looking at the thermography machine that shows the blood flow and oxygenation in the hand veins, it is seen that the circulating oxygen in the veins in your hands decreases even in a single breath. This applies to the whole body. The same thing happens with your skin. The entire skin of people who quit smoking changes in about 90 days; gray-yellow, matte, with large pores; pink-white, There is a transition to a shiny skin with small pores. Your relatives will notice this change with amazement. In fact, there are many who are faced with the question of ‘what did you do to your skin’. Of course, quitting smoking is positive for health in every way, but I wrote it in the hope that knowing that your appearance will rejuvenate rapidly will be effective in your decision to quit smoking in 2022. Because we mostly judge rejuvenation by how we look. When you look in the mirror you don’t see the condition of your lungs, but looking at your face and realizing that you look younger is very motivating. Of course, quitting smoking is positive for health in every way, but I wrote it in the hope that knowing that your appearance will rejuvenate rapidly will be effective in your decision to quit smoking in 2022. Because we mostly judge rejuvenation by how we look. When you look in the mirror you don’t see the condition of your lungs, but looking at your face and realizing that you look younger is very motivating. Of course, quitting smoking is positive for health in every way, but I wrote it in the hope that knowing that your appearance will rejuvenate rapidly will be effective in your decision to quit smoking in 2022. Because we mostly judge rejuvenation by how we look. When you look in the mirror you don’t see the condition of your lungs, but looking at your face and realizing that you look younger is very motivating.
Problems with breathing
First of all, we should put sleep apnea on this list. It’s a much more common problem than you might think. If you have noticed that your spouse stops breathing from time to time at night, I suggest you take him to a sleep laboratory. The rate at which sleep apnea ages you competes with cigarettes and even surpasses it. During apnea, your oxygen level may drop to 80 when your breathing stops, instead of the normal level of 96 and above. This is a real moment of suffocation for the body. You should not object and start wearing the devices used for apnea.
If there is a deviation in the nose, you will still have breathing problems. You should have it treated. Allergic bodies may have a stuffy nose. If you cannot identify the substances you are allergic to, you can support yourself by reducing dairy products. You can sleep by wearing nose strips on your nose.
Superficial and frequent breathing may also occur in panic attack-like situations. Pay attention to whether you are holding your breath during the day. If so, try to stay calm and take deep breaths.
Snoring also reduces your breathing. If it heals with surgery, fix it. Most uku apnea and snoring conditions are more common in overweight people. Going down to a healthy weight should also be one of your goals this year.
Being at a healthy weight
Being at a healthy weight is not a situation that can be detected only on the scale, as you think. The issue is where unwanted fat is stored. Although your weight seems normal, if you have visceral fat, you are not in ideal conditions. To understand whether you have visceral fat, you should check the lubrication in your waist area and abdomen. Waist circumference of 88 cm and above in women and 102 cm and above in men indicates that you have visceral fat. Aim for your goal this year to be at least 20% below these inches. For this, the first thing you will do is to delay the dinner and lighten its content. Yes, we are not weighing this year, we are measuring with a tape measure.
Damages from sugar
It is said that sugar is sweet poison. But if you say which sugar, of course, we are talking about the sugar in processed white sugar, processed flours, ready-made desserts and instant drinks. We call these foods simple carbohydrates for short. The more simple carbohydrates we eat, the faster we age. If you ask why, these foods have a high capacity to break down our body’s proteins. There is an unhealthy interaction between certain proteins in our skin, joints, brain, in short, in our entire body, and the sugar that comes from these foods. This chemical event, whose medical name is glycation, does not return once it happens. In other words, every time you eat these foods, you will see irreversible protein damage. Residues called AGE are formed that age you fast. The abbreviation of AGE, just like its name, is the cause of aging. Even the wrinkle on your skin is a projection of this condition.
Foods that cause AGE and foods that make your visceral fat and thicken your waist are in the same group. So we should add to our diet this year the goal of delaying dinner and eliminating processed carbohydrates. Even that much will go a long way towards staying young.
Moving life
The importance of exercise is repeatedly emphasized. But my purpose here is to encourage you to be a little more active. You don’t need to go to the gym, just add outdoor walks to your life.
Set your circadian internal clocks
The mismatch between the circadian internal clock and the external clock is the topic that ages you the fastest. The circadian internal clock is adjusted to the sun. Waking up with the sun, avoiding exposure to the bright light of electronics after sunset is the simplest internal clock adjustment you can make. Maybe in 2022, you can aim to reduce the long-term staring at the screens of electronics, which we missed in the past pandemic years. It is enough to look only during the day and not to look at night hours when the sun is not normally. Remember, our natural circadian 24-hour internal clock is written entirely in our genes and is adjusted to the sun. Even if you do not immediately see the negative effects on your health as you become stubborn, be sure that this situation will age you very quickly. This year, aim to start the day by touching the sunlight.
Sleep
The most important day of the circadian internal clock adjustment should start with the sun, and end the day with sufficient darkness. In order not to disrupt our melatonin hormone production, which starts at 21 o’clock, we should never look at electronics, especially during these hours. It is necessary to replace the bright lights in the house with lamps that give yellow-red light. They should not be shiny either. At 23 o’clock, we should go to sleep in our full dark room. These are essential for producing healthy melatonin. If there is light, there is no melatonin. Without melatonin, there is no health. Melatonin isn’t just about sleep. The presence of melatonin is an antioxidant. Melatonin is anti-cancer. Melatonin reduces dementia. Melatonin reduces inflammation. The best source for melatonin is our own melatonin production. The first condition for this is to sleep in a dark room after 21 o’clock with little light and at 23 o’clock.
Stress management
Everyone can find a way in this regard. Yoga, meditation, breathing exercises; being in nature, having pets, hobbies, etc. you can apply whatever helps you feel good. You should know that the stress hormones we produce in every stressful situation disrupt your healing, regeneration and rejuvenation process.
We can add a lot more to the above list in order to be rejuvenated in 2022. But even that much gives you cellular life. If the year 2022 is 12 months, maybe you will age 11 months, maybe 10 months, maybe 8 months. You don’t have to age 365 days on the cellular level just because the year is 365 days. With a little attention, you can save a ton of days and put your cells in a state where they haven’t experienced those days yet.
I wish you a year full of youth.
As we enter each new year, we promise ourselves to strive to be healthier. In this article, I will give you some suggestions that will help you stay healthy with small habit changes you can make in 2022. I will give you tips on keeping your biological age younger than your calendar age.
First, let’s find out what makes us age fast. Then let’s make suggestions to correct these negative conditions. What are the cellular causes that age us fast?
Cellular oxygen deficiency
Oxygen must be able to reach each cell sufficiently and the cell must be able to use this oxygen correctly. What could be the reasons why oxygen cannot reach the cell sufficiently?
Smoking
When cigarettes are inhaled, apart from the negative effects of harmful chemicals on health, the lack of oxygen caused by cigarettes is our main concern. Breathing cigarette smoke instead of getting oxygen with each breath reduces the oxygen going to the cells. This creates an entire hypoxia, that is, a lack of oxygen, not just the lungs. You only associate smoking with lung cancer or heart disease, but the picture is bigger. Less oxygen in the breath reduces the oxygen in the microcirculation throughout the body. When looking at the thermography machine that shows the blood flow and oxygenation in the hand veins, it is seen that the circulating oxygen in the veins in your hands decreases even in a single breath. This applies to the whole body. The same thing happens with your skin. The entire skin of people who quit smoking changes in about 90 days; gray-yellow, matte, with large pores; pink-white, There is a transition to a shiny skin with small pores. Your relatives will notice this change with amazement. In fact, there are many who are faced with the question of ‘what did you do to your skin’. Of course, quitting smoking is positive for health in every way, but I wrote it in the hope that knowing that your appearance will rejuvenate rapidly will be effective in your decision to quit smoking in 2022. Because we mostly judge rejuvenation by how we look. When you look in the mirror you don’t see the condition of your lungs, but looking at your face and realizing that you look younger is very motivating. Of course, quitting smoking is positive for health in every way, but I wrote it in the hope that knowing that your appearance will rejuvenate rapidly will be effective in your decision to quit smoking in 2022. Because we mostly judge rejuvenation by how we look. When you look in the mirror you don’t see the condition of your lungs, but looking at your face and realizing that you look younger is very motivating. Of course, quitting smoking is positive for health in every way, but I wrote it in the hope that knowing that your appearance will rejuvenate rapidly will be effective in your decision to quit smoking in 2022. Because we mostly judge rejuvenation by how we look. When you look in the mirror you don’t see the condition of your lungs, but looking at your face and realizing that you look younger is very motivating.
Problems with breathing
First of all, we should put sleep apnea on this list. It’s a much more common problem than you might think. If you have noticed that your spouse stops breathing from time to time at night, I suggest you take him to a sleep laboratory. The rate at which sleep apnea ages you competes with cigarettes and even surpasses it. During apnea, your oxygen level may drop to 80 when your breathing stops, instead of the normal level of 96 and above. This is a real moment of suffocation for the body. You should not object and start wearing the devices used for apnea.
If there is a deviation in the nose, you will still have breathing problems. You should have it treated. Allergic bodies may have a stuffy nose. If you cannot identify the substances you are allergic to, you can support yourself by reducing dairy products. You can sleep by wearing nose strips on your nose.
Superficial and frequent breathing may also occur in panic attack-like situations. Pay attention to whether you are holding your breath during the day. If so, try to stay calm and take deep breaths.
Snoring also reduces your breathing. If it heals with surgery, fix it. Most uku apnea and snoring conditions are more common in overweight people. Going down to a healthy weight should also be one of your goals this year.
Being at a healthy weight
Being at a healthy weight is not a situation that can be detected only on the scale, as you think. The issue is where unwanted fat is stored. Although your weight seems normal, if you have visceral fat, you are not in ideal conditions. To understand whether you have visceral fat, you should check the lubrication in your waist area and abdomen. Waist circumference of 88 cm and above in women and 102 cm and above in men indicates that you have visceral fat. Aim for your goal this year to be at least 20% below these inches. For this, the first thing you will do is to delay the dinner and lighten its content. Yes, we are not weighing this year, we are measuring with a tape measure.
Damages from sugar
It is said that sugar is sweet poison. But if you say which sugar, of course, we are talking about the sugar in processed white sugar, processed flours, ready-made desserts and instant drinks. We call these foods simple carbohydrates for short. The more simple carbohydrates we eat, the faster we age. If you ask why, these foods have a high capacity to break down our body’s proteins. There is an unhealthy interaction between certain proteins in our skin, joints, brain, in short, in our entire body, and the sugar that comes from these foods. This chemical event, whose medical name is glycation, does not return once it happens. In other words, every time you eat these foods, you will see irreversible protein damage. Residues called AGE are formed that age you fast. The abbreviation of AGE, just like its name, is the cause of aging. Even the wrinkle on your skin is a projection of this condition.
Foods that cause AGE and foods that make your visceral fat and thicken your waist are in the same group. So we should add to our diet this year the goal of delaying dinner and eliminating processed carbohydrates. Even that much will go a long way towards staying young.
Moving life
The importance of exercise is repeatedly emphasized. But my purpose here is to encourage you to be a little more active. You don’t need to go to the gym, just add outdoor walks to your life.
Set your circadian internal clocks
The mismatch between the circadian internal clock and the external clock is the topic that ages you the fastest. The circadian internal clock is adjusted to the sun. Waking up with the sun, avoiding exposure to the bright light of electronics after sunset is the simplest internal clock adjustment you can make. Maybe in 2022, you can aim to reduce the long-term staring at the screens of electronics, which we missed in the past pandemic years. It is enough to look only during the day and not to look at night hours when the sun is not normally. Remember, our natural circadian 24-hour internal clock is written entirely in our genes and is adjusted to the sun. Even if you do not immediately see the negative effects on your health as you become stubborn, be sure that this situation will age you very quickly. This year, aim to start the day by touching the sunlight.
Sleep
The most important day of the circadian internal clock adjustment should start with the sun, and end the day with sufficient darkness. In order not to disrupt our melatonin hormone production, which starts at 21 o’clock, we should never look at electronics, especially during these hours. It is necessary to replace the bright lights in the house with lamps that give yellow-red light. They should not be shiny either. At 23 o’clock, we should go to sleep in our full dark room. These are essential for producing healthy melatonin. If there is light, there is no melatonin. Without melatonin, there is no health. Melatonin isn’t just about sleep. The presence of melatonin is an antioxidant. Melatonin is anti-cancer. Melatonin reduces dementia. Melatonin reduces inflammation. The best source for melatonin is our own melatonin production. The first condition for this is to sleep in a dark room after 21 o’clock with little light and at 23 o’clock.
Stress management
Everyone can find a way in this regard. Yoga, meditation, breathing exercises; being in nature, having pets, hobbies, etc. you can apply whatever helps you feel good. You should know that the stress hormones we produce in every stressful situation disrupt your healing, regeneration and rejuvenation process.
We can add a lot more to the above list in order to be rejuvenated in 2022. But even that much gives you cellular life. If the year 2022 is 12 months, maybe you will age 11 months, maybe 10 months, maybe 8 months. You don’t have to age 365 days on the cellular level just because the year is 365 days. With a little attention, you can save a ton of days and put your cells in a state where they haven’t experienced those days yet.
I wish you a year full of youth.
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What is ‘inflammaging’? Here's how inflammation affects you differently as you age.
It happens to everyone. With age come discomforts: achy joints, wounds that heal more slowly, and a rising risk for cancers, heart disease, dementia, arthritis, and other illnesses. Those changes follow an uptick in inflammatory molecules over the course of a lifetime, according to a large and growing body of research. The link between age, inflammation, and disease is so well established, it has a name: inflammaging.
Now, researchers are unraveling the details of how the inflammatory process changes over the lifespan, what instigates the shift, and how it might be possible to interfere with the process. The work suggests interventions ranging from new drugs to new motivations for healthy habits like exercise that can slow the aging process, says Ron DePinho, a cancer biology and aging researcher at the University of Texas MD Anderson Cancer Center in Houston.
Research on inflammaging also illustrates the nuanced challenge of taking the reins of inflammation to sustain health later in life. Although many people fixate on the need to reduce inflammation, it is more important to sustain the appropriate amount of it as a means toward extending quality rather than quantity of life, says Judith Campisi, a cell biologist at the Buck Institute for Research on Aging, an independent research facility in Novato, Calif.
“What happens with age is you lose control of inflammation,” she says. “Even if you’re five years old, you will never heal a wound without an initial inflammatory response. It’s not always bad. It’s sometimes good.”
Hallmarks of aging
As people age, according to numerous studies, increasing amounts of pro-inflammatory cytokines and other inflammation-related molecules circulate in the blood alongside a rise in localized inflammation. When the shift occurs depends on the person, DePinho says, but 50 is generally when inflammation starts to increase, with a dramatic shift after 60.
That uptick tracks closely with disease trends. Beginning in the early sixties, risks rise substantially for the most common chronic diseases of aging: cancer, diabetes, heart disease and dementia, DePinho says. Starting at 65, the number of people with Alzheimer’s doubles every five years. In the U.S., 80 percent of adults over 65 have at least one chronic condition. By age 85, a third of people may have Alzheimer’s, while a third of men and one-fourth of women have had cancer. People with more inflammation in their bodies have a higher risk of disease.
Scientists have identified a dozen biological changes that correspond with age. All of those hallmarks of aging are associated with inflammation, and inflammation is considered a pillar of aging, says Luigi Ferrucci, a geriatrician and epidemiologist at the Intramural Research Program of the NIH’s National Institute on Aging in Baltimore, Maryland.
For example, as people get older, their immune cells lose their protective functions and stop doing the job of fighting off invaders, turning into what scientists call senescent cells. Other kinds of cells can also become senescent in response to stress. They cease replicating, no longer do their jobs, and start to secrete powerful inflammatory molecules that cause yet more cells to become senescent in a self-perpetuating cycle.
A relentless loop
Meanwhile, DNA damage inside cells accumulates over time, especially at the tips of chromosomes in protective regions called telomeres, which are long stretches of bunched-up DNA. Each time a cell divides, its telomeres become shorter until they reach a critical length that is perceived by the cell as DNA damage or instability, which may induce cellular senescence.
As telomeres become damaged, they initiate a signaling process through proteins that turn certain genes on and off. Some of the genes affected support the function of mitochondria (the cell components that produce energy). As a result of the gene disruption, mitochondria become defective and leak their DNA into cells, sparking inflammation.
Scientists used to consider telomere shortening, mitochondrial damage, inflammation, and other processes as separate theories of aging that could contribute to diseases like cancer, DePinho says. Now it is clear that all of these changes are connected and that inflammation acts like a “co-conspirator” in the aging process.
As chronic inflammation sets in, it becomes harder for the immune system to perform routine tasks, like detecting and eliminating cancer cells and pathogens, which could make people more likely to develop diseases. Inflammation in the body may also activate immune cells in the brain called microglia, according to one theory, causing inflammation, weakening the blood-brain barrier, and destroying nerve cells, ultimately contributing to the development of Alzheimer’s.
This burgeoning understanding of inflammaging as a relentless circuit of steps that all exacerbate inflammation is revealing new ways to break the cycle.
Aging better
Efforts to develop anti-aging interventions that target inflammation are challenging because they need to be specific to avoid causing more harm than good, Ferrucci says. Trying to tackle the chronic inflammation of aging with general anti-inflammatory drugs, for example, could make people more susceptible to disease by impairing the inflammation that our bodies need for staying healthy. “When you have an infection, if you don’t have inflammation, you’re going to die,” Ferrucci says. “Shutting down inflammation with a bomb like a corticosteroid or some monoclonal antibodies works. It’s also quite dangerous.”
One of the most promising new strategies for dealing with inflammaging is attacking senescent cells, experts say. In mice, a low-dose combination of two drugs, called Dasatinib and Quercetin, appears to be particularly effective at getting rid of these deadbeat cells and reducing inflammation in the intestines with the potential to extend lives. Clinical trials are now underway with these and other so-called senolytics to see if the same kinds of compounds might kill senescent cells and break the cycle of inflammation and disease in people too, says DePinho.
Other ongoing approaches include efforts to identify drugs that could restore telomeres, enhance mitochondrial function, and activate anti-aging genes, a strategy DePinho is working on. Some over-the-counter supplements claim to boost levels of proteins called sirtuins, which help cells respond to stresses, and a molecule called NAD+, which helps mitochondria function, among other roles, and dwindles in half from youth to middle age. Although evidence has been seriously questioned and these products have been over-hyped, DePinho says, further study may illuminate new anti-aging properties of sirtuins.
Scientists are hopeful that they are getting closer to understanding which interventions will help most, and studies in mice illustrate the tantalizing possibilities. “Tissues retain a remarkable capacity to renew themselves if you remove the underlying instigators of the aging process,” DePinho says.
Advances in immunology are lending new insights into how we can allow good inflammation to proceed while squashing the bad that can come from too much of it, Ferrucci adds. “As we discover the nuances of inflammation,” he says, “then it may be possible to find drugs that do not shut down inflammation completely.”
Age-fighting behaviors
For now, there are simple steps people can take to address inflammaging in their own bodies, experts say, including exercise. Regular physical activity enhances DNA repair, improves mitochondrial function, activates sirtuins, and, studies show, can reduce the risk of cancer, diabetes, heart disease, and Alzheimer’s. Regular vigorous activity is best, but as little as 15 minutes a day can make a difference, DePinho says, and even leisure activities help.
Dietary choices, too, can improve the chronic inflammatory state of inflammaging, according to a variety of studies that support eating a Mediterranean-style diet with an emphasis on whole grains, produce, nuts, and fish. Eating a wide variety of vegetables may also help sustain the gut microbiome, which tends to become less resilient and contribute to rising levels of inflammation with age. Each Saturday, when Ferrucci goes to the market to shop for the week, he buys 10 different kinds of vegetables, based on this emerging evidence. “That is something that has been suggested in the literature,” he says. “And I think that’s a simple way of following that advice.”
Body fat releases cytokines that promote inflammation, DePinho adds, so using exercise and diet to control weight can have extra benefits. He also advises people to avoid or quit smoking, a habit known to increase DNA damage and drive inflammation. Finding ways to relax is another useful goal, as chronic stress has been linked to shortened telomeres, accelerated aging, and inflammatory diseases. Adequate sleep and meditation can help reduce stress, DePinho says.
Healthy habits like these are important throughout life, Ferrucci says, but they become especially important as the mechanisms that protect our cells from damage become less functional with age. That accumulating damage is a key source of inflammation. “Intervening in any possible way becomes more important as you become older,” he says.
27 сент. 2023 г.
New therapeutic approach against leukemia
Leukemia frequently originates from the so-called leukemic stem cell, which resides in a tumor promoting and protecting niche within the bone marrow. Scientists from the Max Planck Institute of Biochemistry in Martinsried, Germany, have found a new way to make these cells vulnerable by specifically dislodging these cells from their niches.
Since blood cells have a limited lifespan, are lost during bleeding or are used up during infections, they must be replaced continuously. This supply is ensured by the so-called hematopoietic stem cells in the bone marrow. These cells can develop into any type of blood cell.
In chronic myeloid leukemia, the hematopoietic stem cell undergoes a genetic mutation by recombining chromosome 9 and 22. As a result, gene building blocks fuse that would otherwise not be in contact with each other. The incorrectly assembled chromosome is called Philadelphia chromosome and harbors the construction manual for the so-called BCR-ABL oncogene. This causes the leukemic stem cell to behave selfishly and divide at the expense of healthy blood stem cells.
Without Kindlin-3 no leukemia
A leukemic stem cell creates an environment termed the malignant niche that ensure its survival and proliferation. To remain in this tumor-promoting niche, the leukemic stem cell uses so-called integrins to attach itself to a scaffold of extracellular proteins, the so-called extracellular matrix, and to neighboring cells. In the leukemic stem cell, the activity and function of the integrins is facilitated by an intracellular protein called Kindlin.
Peter Krenn, first author of the study, explains: “The isoform Kindlin-3 is only used by blood cells. If mice harbor leukemic stem cells that lack Kindlin-3, they do not develop leukemia. Without Kindlin-3 and active integrins, the leukemic stem cells cannot attach themselves to their niche environment and are released from the bone marrow into the blood. Since they cannot home elsewhere either, they remain in the blood. There the leukemic stem cells lack the urgently needed support, which they usually receive from the niche, and die.”
New therapeutic approach: Kindlin-3 and CTLA-4
The new finding that the leukemic stem cells express a protein called CTLA-4 on their surface, which is absent from healthy blood stem cells, allowed the researchers to distinguish a leukemic blood stem cell from a healthy blood stem cell. The scientists used the CTLA-4 receptor as a shuttle to deliver a Kindlin-3 destroying compound, into leukemic stem cells. Peter Krenn explains: “CTLA-4 is only briefly present on the cell surface and is then rapidly recycled back into the cell and then back to the cell surface again. This enabled us to introduce a Kindlin-3 degrading siRNA into the cell by coupling it to a CTLA-4-binding RNA sequence, which is called aptamer. The leukemic stem cell without Kindlin-3 is flushed from the bone marrow and the leukemia loses its origin and runs out of fuel.”
Peter Krenn summarizes: “In our current study we have developed a new therapeutic approach to treat chronic myeloid leukemia in mice. However, the principle of the therapy is universally valid. The inhibited Kindlin-3 production and consequent loss of integrin function prevents the cancer cells from being able to adhere and settle in tumor-promoting niches. I assume that this method will also prevent the cancer cells of other types of leukemia from settling and that these diseases could thus become much more treatable.”
Max-Planck-Gesellschaft. (2020, October 23). New therapeutic approach against leukemia. ScienceDaily. Retrieved November 16, 2020 from resource link.
23 окт. 2020 г.
Reversing age- and Glaucoma-induced vision loss
One proposed cause of aging is the accumulation of epigenetic noise – or disruptions in gene expression patterns – that lead to decreased tissue function and reduced regenerative abilities. In a recent study, researchers from the Harvard Medical School (HMS) addressed the epigenetics-based theory of aging which postulates that changes in the epigenome cause cellular malfunctions and age-related diseases over time.
Their research continues to explore whether DNA methylation drives cellular change and whether restoring functionality in living organisms is possible. Results report restored vision in mice achieved by restoring aged cells in the retina to their youthful function and a reversal of vision loss in mice with a condition mimicking human glaucoma.
Epigenetic reprogramming in mice
The proof-of-concept study represents the first successful attempt at reversing the biological clock in animals via epigenetic reprogramming. To prove this, the team of researchers examined the potential of reversing the age of cells by controlling DNA methylation.
Led by Yuancheng Lu, research fellow at Harvard Medical School, the study’s authors examined whether the regenerative capacity of young animals can be replicated in adult mice by delivering a modified three-gene combination via an adeno-associated virus (AAV) into the retinal ganglion cells of adult mice with optic nerve injury. They targeted cells within the central nervous system as it is the first part of the body affected by aging.
“Having previously found evidence for epigenetic noise as an underlying cause of aging, we wondered whether mammalian cells might retain a faithful copy of epigenetic information from earlier in life that could serve as instructions to reverse aging,”” the research team commented.
Restoring eyesight and rejuvenating cells
Lu and colleagues found that the treatment had multiple beneficial effects on the eye health of mice; it promoted nerve regeneration following optic nerve injury in mice with damaged optic nerves, caused a two-fold increase in the number of surviving retinal ganglion cells after injury, and increased nerve regrowth by five times. These results suggested that the modified gene combination approach was safe and could potentially be used to revolutionize the treatment of ocular degeneration as well as that of other organs affected by aging.
Following their promising findings, Lu and his team partnered with colleagues at Schepens Eye Research Institute of Massachusetts to perform two experiments: one testing whether the three-gene cocktail could restore glaucoma-related vision loss and a second one to test whether this approach could reverse vision loss associated with the regular biological aging process.
The team found that the treatment led to increased nerve cell electrical activity as well as a notable increase in visual acuity, which was measured by the animals’ ability to see moving vertical lines across a screen in a model of glaucoma. “To our knowledge, this is the first example of vision-loss reversal after glaucomatous injury has occurred; previous attempts have focused on neuroprotection delivered at an early stage to prevent further disease progression,” the authors wrote.
Similarly, the treatment had beneficial effects on the vision of elderly mice; it was able to restore vision in older mice with diminishing vision caused by normal aging. Following the treatment, the researchers found reversed patterns of DNA methylation which suggest that DNA methylation is an active agent in the aging process.
“These data indicate that mammalian tissues retain a record of youthful epigenetic information—encoded in part by DNA methylation—that can be accessed to improve tissue function and promote regeneration in vivo,” the authors concluded.
Clinical implications
As the first findings that prove the reversal of glaucoma-induced vision loss with no associated negative side effects in the cohort, the latest results will need to be confirmed in further animal work before human trials can be initiated. Nonetheless, the success of the new approach represents a potential breakthrough in regenerative medicine and an array of possible treatment pathways for age-related health conditions.
“Our study demonstrates that it’s possible to safely reverse the age of complex tissues such as the retina and restore its youthful biological function,” said David Sinclair, PhD, co-director of the Paul F. Glenn Center for Biology of Aging Research at HMS, who is senior author of the published paper in Nature. “If affirmed through further studies, these findings could be transformative for the care of age-related vision diseases like glaucoma and to the fields of biology and medical therapeutics for disease at large,” he explained.
9 нояб. 2021 г.
Scientists repair injured spinal cord using patients' own stem cells
Intravenous injection of bone marrow derived stem cells (MSCs) in patients with spinal cord injuries led to significant improvement in motor functions, researchers from Yale University and Japan report Feb. 18 in the Journal of Clinical Neurology and Neurosurgery.
For more than half of the patients, substantial improvements in key functions — such as ability to walk, or to use their hands — were observed within weeks of stem cell injection, the researchers report. No substantial side effects were reported.
The patients had sustained, non-penetrating spinal cord injuries, in many cases from falls or minor trauma, several weeks prior to implantation of the stem cells. Their symptoms involved loss of motor function and coordination, sensory loss, as well as bowel and bladder dysfunction. The stem cells were prepared from the patients’ own bone marrow, via a culture protocol that took a few weeks in a specialized cell processing center. The cells were injected intravenously in this series, with each patient serving as their own control. Results were not blinded and there were no placebo controls.
Yale scientists Jeffery D. Kocsis, professor of neurology and neuroscience, and Stephen G. Waxman, professor of neurology, neuroscience and pharmacology, were senior authors of the study, which was carried out with investigators at Sapporo Medical University in Japan. Key investigators of the Sapporo team, Osamu Honmou and Masanori Sasaki, both hold adjunct professor positions in neurology at Yale.
Kocsis and Waxman stress that additional studies will be needed to confirm the results of this preliminary, unblinded trial. They also stress that this could take years. Despite the challenges, they remain optimistic.
“Similar results with stem cells in patients with stroke increases our confidence that this approach may be clinically useful,” noted Kocsis. “This clinical study is the culmination of extensive preclinical laboratory work using MSCs between Yale and Sapporo colleagues over many years.”
“The idea that we may be able to restore function after injury to the brain and spinal cord using the patient’s own stem cells has intrigued us for years,” Waxman said. “Now we have a hint, in humans, that it may be possible.”
Yale University. (2021, Feb
ruary 22). Scientists repair injured spinal cord using patients’ own stem cells. ScienceDaily. Retrieved May 16, 2021 from
22 февр. 2021 г.
NAD+ can restore age-related muscle deterioration, research finds
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10 нояб. 2021 г.