Inflammation and senile fractures
The aggravation of chronic inflammation, and not old age itself, is the main cause of age-related deterioration of the ability of bones to repair damage. Such conclusions were reached by researchers from the New York University School of Medicine, working under the guidance of Dr. Philipp Leucht (Philipp Leucht).
Diseases that weaken bone tissue are among the most common age-related pathologies. Bone fractures are rarely fatal, but they can greatly reduce the quality of life, especially in old age, when some fractures never heal.
The study conducted by the authors was based on the observation that the number of stem cells in the human bone marrow decreases significantly with age and, in parallel, the healing process of fractures slows down. To study the underlying mechanisms of this relationship, the researchers conducted a series of experiments on mouse models.
Bone tissue in the immediate vicinity of the fracture zone with a bone marrow full of red blood cells, below, healthy bone tissue colored brown, above it, new bone tissue green and cartilage tissue in the upper layer colored dark blue.
As a result, they demonstrated that exposure to blood serum from old mice reduces the ability of stem cells of young animals to divide and multiply by 4 times due to their entry into the so-called phase of physiological aging. Earlier studies have also shown that cells entering this phase release inflammatory-stimulating signals, thus triggering a vicious circle.
In particular, it turned out that the effect of serum from old mice on young stem cells indirectly activates the transcription factor NF-kB (nuclear factor kappa-bi), which plays a key role in triggering the immune response. NF-kB interacts with DNA by activating several pro-inflammatory genes. Experiments have shown that signals from this particular protein cause bone stem cells to stop dividing.
Moreover, prolonged therapy with sodium salicylate, the active ingredient of aspirin, suppressed NF–kB signals and associated age–related chronic inflammation. This ensured an increase in the number of bone stem cells and an increase in their activity in the healing processes of damage. Further experiments showed that anti-inflammatory therapy changed the activity of thousands of genes in stem cells, restoring their genetic profile to a state characteristic of a young organism.
According to the authors, the results obtained indicate that the age-related impairment of the ability of bone tissue to recover is due not to chronological age, but to age-related inflammation (Eng. "inflamm-aging"). Age-related inflammatory processes are triggered by the immune system in response to the accumulation of abnormal molecules in tissues formed as a result of wear and damage.
The authors also note that rejuvenation of bone stem cells with anti-inflammatory drugs immediately after a fracture is impractical, since such an intervention blocks the process of acute inflammation, which is a necessary component of a successful healing process.
At the same time, anti-inflammatory drugs can be prescribed for several weeks before planned surgical interventions, such as hip or knee replacement. This will provide a preliminary increase in the stem cell population, and the subsequent cancellation of anti-inflammatory therapy will allow the development of an acute inflammatory reaction necessary for normal healing.
In addition, the results of the study at the genetic level indicate the existence of signaling pathways, the impact of which with the help of pharmacological drugs in the future will allow suppressing the effects of age-related chronic inflammation on stem cells, without compromising the "beneficial" inflammation that is rapidly developing in response to bone damage.
Article by Josephson et al. Age-related inflammation triggers skeletal stem/progenitor cell dysfunction is published in the journal Proceedings of the National Academy of Sciences.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru according to NYU Langone Hospitals: 'Inflamm-aging' Causes Loss of Bone Healing Ability in the Elderly.