Inflammaging – could ibuprofen be the answer?

Neurodegenerative disease is associated with age-related chronic, low grade inflammation, but studies suggest that this could be reversed with over the counter NSAIDs.

In an ever-aging population, neurodegenerative disease is a major cause of age associated disability and shortened lifespan [1].

Longevity.Technology: Inflammation is a central pillar of aging (areas of geroscience and age-releated research). The six other pillars – stem cell regeneration, stress, macromolecular damage, proteostasis and metabolism converge on inflammation, affecting and affected by it. Closely associated with age-related morbidity and mortality, inflammation is thought to accelerate the process of biological aging and to worsen many age-related diseases. One popular drug, metformin, has already been shown to repair broken cell machinery and drastically lower dangerous inflammation, and now ibuprofen could become an over-the-counter treatment.

During aging, chronic low grade inflammation develops, contributing to the onset of age-related diseases such as Alzheimer’s and Parkinson’s; this process is referred to as inflammaging. Inflammaging is caused by chronic activation of the immune system over tine and the degeneracy of receptors within the immune system that can distinguish “self”, “non-self” and signals of damage [2]. This process leads to tissue degeneration, damage of cellular components and activation of cell death pathways, which are all damaging to the body.

Scientists at the Biosciences Institute for Ageing Research in Newcastle in the UK, have created a mouse model to mimic the effects of inflammaging . These mice had genetically enhanced NF-𝚔B activity which predisposed them to chronic low-grade inflammation and premature aging. NF-𝚔B is a transcription factor that regulates genes in both the innate and adaptive immune response. These mice showed symptoms of memory loss, determined by failure to navigate a maze, filled with visual cues to which they had previously become accustomed in training (the Barnes maze test).

Ibuprofen inhibits cyclooxygenase enzyme COX-2, an enzyme that could be associated with the induction of cellular senescence.

Short-term memory was tested on day 5 and long-term memory on day 12, with no training in between tests. These mice showed signs of inflammation in the brain, determined by an increase in cytokine production (chemical messengers produced by activated immune cells that are involved in inflammatory pathways) in the central nervous system. Interestingly, in the areas of the brain associated with memory – the hippocampus and cerebellum – an increased number of senescent cells were found.

Senescence occurs when a cell can no longer divide and make new cells, and it has been shown to contribute to neurodegeneration and chronic inflammation. This phenomenon is known as the Hayflick limit – a normal human cell can only replicate and divide 40-60 times before, after which it will break down by programmed cell death or apoptosis. Senescent cells are dangerous because they express inflammation-associated genes and secrete matrix metalloproteinases and inflammatory cytokines that can damage the surrounding tissues.

Long term treatment with ibuprofen, an over the counter non-steroidal anti-inflammatory drug was shown to reduce markers of senescence in neurons as well as brain inflammation in these aging mice [3].

Ibuprofen inhibits cyclooxygenase enzyme COX-2, an enzyme that could be associated with the induction of cellular senescence. Ibuprofen may also impact pathways contributing to the over production of reactive oxygen species (ROS) which can lead to telomere dysfunction and senescence, which can ultimately contribute to inflammation [3].

… inhibition of COX with anti-inflammatory medications could help to reduce the detrimental effect that aging has on cognition.

Other pre-clinical studies have associated COX inhibitor administration with improved cognitive performance and reduced inflammaging [4,5]. This suggests that inhibition of COX with anti-inflammatory medications could help to reduce the detrimental effect that aging has on cognition.

Clinical studies so have not supported the use of NSAIDs in the treatment of Alzheimer’s disease, but there is some evidence to suggest that ibuprofen could reduce the risk of developing Parkinson’s disease [6,7]. In four studies that examined the impact of ibuprofen treatment alone, a 27% reduction in risk of developing Parkinson’s disease was shown. It is important to note that no information was gathered to determine if there were any adverse effects associated with ibuprofen use in these studies.

Further research is necessary to determine whether early intervention with NSAIDs such as ibuprofen could help to slow the process of inflammaging and ultimately prevent the onset of neurodegeneration. Ibuprofen is an over-the-counter medication that is cheap and readily available. It has been used as a pain killer for many years and thereafter there is an abundance of data supporting its safe use, so using it to counter inflammaging would good news for Longevity.


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