Breakthrough osteoporosis treatment called the Fountain of Youth
As we age, our bones become thinner, we suffer fractures more often, and bone-diseases such as osteoporosis are more likely to occur.
[Jan. 10, 2023: Maren Berghoff, Max-Planck-Gesellschaft]
This fountain of youth for the epigenome could become important for the treatment of diseases such as osteoporosis (CREDIT: Creative Commons)
As we age, our bones become thinner, we suffer fractures more often, and bone-diseases such as osteoporosis are more likely to occur. One responsible mechanism involves the impaired function of the bone-marrow stem cells, which are required for the maintenance of bone integrity.
Researchers from the Max Planck Institute for Biology of Ageing and CECAD Cluster of Excellence for Ageing Research at the University of Cologne have now shown that the reduced stem cell function upon aging is due to changes in their epigenome. They were able to reverse these changes in isolated stem cells by adding acetate. This fountain of youth for the epigenome could become important for the treatment of diseases such as osteoporosis.
Aging Researchers have been looking at epigenetics as a cause of ageing processes for some time. Epigenetics looks at changes in genetic information and chromosomes that do not alter the sequence of the genes themselves, but do affect their activity. One possibility is changes in proteins called histones, which package the DNA in our cells and thus control access to DNA.
The Cologne research group of Peter Tessarz has now studied the epigenome of mesenchymal stem cells. These stem cells are found in bone marrow and can give rise to different types of cells such as cartilage, bone and fat cells.
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"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."
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)
Rejuvenation of the epigenome
The researchers then investigated whether the epigenome of stem cells could be rejuvenated. To do this, they treated isolated stem cells from mouse bone marrow with a nutrient solution which contained sodium acetate.
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, CpG islands and possibly enhancers. Chromatin remodelling complexes alter chromatin structure to create an accessible chromatin for the binding of transcriptional regulatory factors like transcription factors, coactivators and the basal transcription machinery including RNA polymerase II. Actively transcribed genes are marked by active histone methylation H3K4me3 and active histone acetylation like H3K9ac at the transcription start site by histone modifiers like histone acetylases and histone methylases. Histone variants like H2A.Z and H3.3 mark nucleosome-free regions of transcriptionally active promoters and other regulatory elements. NcRNAs are involved in maintaining the heterochromatic regions. (CREDIT: Future Science Group 2010)
The cell converts the acetate 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 clarify whether this change in the epigenome could also be the cause of the increased risk in old age for bone fractures or osteoporosis in humans, 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.
A new therapeutic approach against osteoporosis?
"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.
What are the symptoms of osteoporosis?
Usually, there are no symptoms of osteoporosis. That is why it is sometimes called a silent disease. However, you should watch out for the following things:
Loss of height (getting shorter by an inch or more).
Change in posture (stooping or bending forward).
Shortness of breath (smaller lung capacity due to compressed disks).
Bone fractures.
Pain in the lower back.
Who is at risk for developing osteoporosis?
There are many risk factors that increase your chance of developing osteoporosis, with two of the most significant being gender and age.
Everyone’s risk for osteoporosis fractures increases with age. However, women over the age of 50 or postmenopausal women have the greatest risk of developing osteoporosis. Women undergo rapid bone loss in the first 10 years after entering menopause, because menopause slows the production of estrogen, a hormone that protects against excessive bone loss.
Age and osteoporosis affect men also. You might be surprised to know that men over the age of 50 are more likely to have an osteoporosis-induced bone break than to get prostate cancer. About 80,000 men per year are expected to break a hip, and men are more likely than women to die in the year after a hip fracture.
Your risk of developing osteoporosis is also linked to ethnicity. Caucasian and Asian women are more likely to develop osteoporosis. However, African-American and Hispanic women are still at risk. In fact, African-American women are more likely than white women to die after a hip fracture.
Another factor is bone structure and body weight. Petite and thin people have a greater risk of developing osteoporosis because they have less bone to lose than people with more body weight and larger frames.
Family history also plays a part in osteoporosis risk. If your parents or grandparents have had any signs of osteoporosis, such as a fractured hip after a minor fall, you may have a greater risk of developing the disease.
Finally, some medical conditions and medications increase your risk. If you have or had any of the following conditions, some of which are related to irregular hormone levels, you and your healthcare provider might consider earlier screening for osteoporosis.
Overactive thyroid, parathyroid, or adrenal glands.
History of bariatric (weight loss) surgery or organ transplant.
Hormone treatment for breast or prostate cancer or a history of missed periods.
Celiac disease, or inflammatory bowel disease.
Blood diseases such as multiple myeloma.
Some medications cause side effects that may damage bone and lead to osteoporosis. These include steroids, treatments for breast cancer, and medications for treating seizures. You should speak with your healthcare provider or pharmacist about the effect of your medications on bones.
It may seem as though every risk factor is related to something that is out of your control, but that’s not true. You do have control over some of the risk factors for osteoporosis. You can discuss medication issues with your healthcare provider. And—you are in charge of your:
Eating habits: You are more likely to develop osteoporosis if your body doesn’t have enough calcium and vitamin D. Although eating disorders like bulimia or anorexia are risk factors, they can be treated.
Lifestyle: People who lead sedentary (inactive) lifestyles have a higher risk of osteoporosis.
Tobacco use: Smoking increases the risk of fractures.
Alcohol use: Having two drinks a day (or more) increases the risk of osteoporosis.
Note: Materials provided above by Max-Planck-Gesellschaft. Content may be edited for style and length.
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