[May 16, 2023: Staff Writer, The Brighter Side of News]
This fountain of youth for the epigenome could become important for the treatment of diseases such as osteoporosis (CREDIT: Creative Commons)
As the population continues to age, the incidence of bone-related diseases such as osteoporosis is on the rise. Researchers have been investigating the mechanisms behind these diseases for some time, and a recent study from the Max Planck Institute for Biology of Ageing and the CECAD Cluster of Excellence for Ageing Research at the University of Cologne has found that changes in the epigenome of bone-marrow stem cells could be responsible.
Epigenetics is the study of changes in genetic information and chromosomes that do not affect the sequence of genes themselves but do alter their activity. The Cologne research group led by Peter Tessarz focused on the epigenome of mesenchymal stem cells, which are found in bone marrow and can give rise to different types of cells, including cartilage, bone, and fat cells.
"We wanted to know why these stem cells produce less material for the development and maintenance of bones as we age, causing more and more fat to accumulate in the bone marrow. To do this, we compared the epigenome of stem cells from young and old mice," explains Andromachi Pouikli, first author of the study. "We could see that the epigenome changes significantly with age. Genes that are important for bone production are particularly affected."
The researchers then investigated whether the epigenome of stem cells could be rejuvenated. They treated isolated stem cells from mouse bone marrow with a nutrient solution containing sodium acetate, which the cells convert into a building block that enzymes can attach to histones to increase access to genes, thereby boosting their activity. "This treatment impressively caused the epigenome to rejuvenate, improving stem cell activity and leading to higher production of bone cells," Pouikli said.
To determine whether this change in the epigenome could also be the cause of the increased risk of bone fractures or osteoporosis in humans as they age, the researchers studied human mesenchymal stem cells from patients after hip surgery. The cells from elderly patients who also suffered from osteoporosis showed the same epigenetic changes as previously observed in the mice.
Stained calcium (dark brown) in stem cells from the bone marrow: Young stem cells (left) produce more material for bone than old stem cells (center). They can be rejuvenated by adding sodium acetate (right). (Credit: Pouikli/Max Planck Institute for Biology of Aging)
"Sodium acetate is also available as a food additive, however, it is not advisable to use it in this form against osteoporosis, as our observed effect is very specific to certain cells. However, there are already first experiences with stem cell therapies for osteoporosis. Such a treatment with acetate could also work in such a case. However, we still need to investigate in more detail the effects on the whole organism in order to exclude possible risks and side effects," explains Peter Tessarz, who led the study.
The epigenome. The epigenome is characterized by the complex interactions of DNA methylation, chromatin remodelling complexes, histone modifications, histone variants, histone modifying enzymes and other factors like ncRNAs. DNA methylation is present all throughout the genome except at promoter regions. (CREDIT: Future Science Group 2010)
Osteoporosis is a condition where bones become weak and brittle and are more likely to break. It is a common condition among older adults, particularly women, and can lead to significant pain, disability, and loss of independence. According to the National Osteoporosis Foundation, approximately 54 million Americans have osteoporosis or low bone mass, putting them at risk for fractures.
Current treatments for osteoporosis include medications that slow down bone loss or increase bone density, as well as lifestyle changes such as regular exercise and a diet rich in calcium and vitamin D. However, these treatments may not be effective for everyone, and there is a need for new therapies that target the underlying mechanisms behind the disease.
The CiC–histone acetylation-cell fate axis is conserved in human MSCs upon aging. (CREDIT: Nature Aging)
The findings from the Max Planck Institute and University of Cologne study suggest that targeting the epigenome of bone-marrow stem cells could be a promising therapeutic approach. By reversing the epigenetic changes that occur with age, it may be possible to improve stem cell activity and promote the production of bone cells, thereby reducing the risk of fractures and osteoporosis.
Symptoms of Osteoporosis
Osteoporosis is called a “silent” disease” because there are typically no symptoms until a bone is broken. Symptoms of vertebral (spine) fracture include severe back pain, loss of height, or spine malformations such as a stooped or hunched posture (kyphosis).
Bones affected by osteoporosis may become so fragile that fractures occur spontaneously or as the result of:
Minor falls, such as a fall from standing height that would not normally cause a break in a healthy bone.
Normal stresses such as bending, lifting, or even coughing.
Causes of Osteoporosis
Osteoporosis occurs when too much bone mass is lost and changes occur in the structure of bone tissue. Certain risk factors may lead to the development of osteoporosis or can increase the likelihood that you will develop the disease.
Many people with osteoporosis have several risk factors, but others who develop osteoporosis may not have any specific risk factors. There are some risk factors that you cannot change, and others that you may be able to change. However, by understanding these factors, you may be able to prevent the disease and fractures.
Factors that may increase your risk for osteoporosis include:
Sex. Your chances of developing osteoporosis are greater if you are a woman. Women have lower peak bone mass and smaller bones than men. However, men are still at risk, especially after the age of 70.
Age. As you age, bone loss happens more quickly, and new bone growth is slower. Over time, your bones can weaken and your risk for osteoporosis increases.
Body size. Slender, thin-boned women and men are at greater risk to develop osteoporosis because they have less bone to lose compared to larger boned women and men.
Race. White and Asian women are at highest risk. African American and Mexican American women have a lower risk. White men are at higher risk than African American and Mexican American men.
Family history. Researchers are finding that your risk for osteoporosis and fractures may increase if one of your parents has a history of osteoporosis or hip fracture.
Changes to hormones. Low levels of certain hormones can increase your chances of developing osteoporosis. For example:
Low estrogen levels in women after menopause.
Low levels of estrogen from the abnormal absence of menstrual periods in premenopausal women due to hormone disorders or extreme levels of physical activity.
Low levels of testosterone in men. Men with conditions that cause low testosterone are at risk for osteoporosis. However, the gradual decrease of testosterone with aging is probably not a major reason for loss of bone.
Diet. Beginning in childhood and into old age, a diet low in calcium and vitamin D can increase your risk for osteoporosis and fractures. Excessive dieting or poor protein intake may increase your risk for bone loss and osteoporosis.
Other medical conditions. Some medical conditions that you may be able to treat or manage can increase the risk of osteoporosis, such as other endocrine and hormonal diseases, gastrointestinal diseases, rheumatoid arthritis, certain types of cancer, HIV/AIDS, and anorexia nervosa.
Medications. Long-term use of certain medications may make you more likely to develop bone loss and osteoporosis, such as:
Glucocorticoids and adrenocorticotropic hormone, which treat various conditions, such as asthma and rheumatoid arthritis.
Antiepileptic medicines, which treat seizures and other neurological disorders.
Cancer medications, which use hormones to treat breast and prostate cancer.
Proton pump inhibitors, which lower stomach acid.
Selective serotonin reuptake inhibitors, which treat depression and anxiety.
Thiazolidinediones, which treat type II diabetes.
Lifestyle. A healthy lifestyle can be important for keeping bones strong. Factors that contribute to bone loss include:
Low levels of physical activity and prolonged periods of inactivity can contribute to an increased rate of bone loss. They also leave you in poor physical condition, which can increase your risk of falling and breaking a bone.
Chronic heavy drinking of alcohol is a significant risk factor for osteoporosis.
Studies indicate that smoking is a risk factor for osteoporosis and fracture. Researchers are still studying if the impact of smoking on bone health is from tobacco use alone or if people who smoke have more risk factors for osteoporosis.
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