Newswise — Researchers from the University of Virginia School of Medicine have made a significant discovery related to aging and chronic inflammation. This finding points to a crucial factor that drives the acceleration of aging and may open doors to extend our lifespan while enjoying better health. Furthermore, it holds the promise of preventing age-related conditions, including fatal heart disease and debilitating brain disorders that deteriorate our cognitive abilities.
The root cause of this harmful inflammation lies in the improper calcium signaling within the mitochondria of specific immune cells. Mitochondria are essential energy producers in cells and heavily depend on calcium signaling.
Led by Bimal N. Desai, PhD, the UVA Health research team found that immune cells known as macrophages experience a decline in their capacity to uptake and use calcium as they age. This deficiency in calcium utilization leads to chronic inflammation, which is responsible for many of the health issues that plague us in our later years. By understanding and addressing this calcium signaling problem, we may have the potential to slow down the aging process and improve the overall quality of life, safeguarding ourselves against age-related diseases.
The researchers are of the opinion that by enhancing calcium uptake in the mitochondrial macrophages, it could be possible to prevent the harmful inflammation and its devastating consequences. As macrophages are present in all organs, including the brain, targeting these "tissue-resident macrophages" using appropriate medications might offer a potential approach to slowing down age-related neurodegenerative diseases.
Bimal N. Desai, from UVA's Department of Pharmacology and UVA's Carter Immunology Center, expressed their belief that they have achieved a crucial breakthrough in comprehending the molecular mechanisms underlying age-related inflammation. This newfound understanding paves the way for novel therapeutic strategies to interrupt the inflammatory processes that contribute to various cardiometabolic and neurodegenerative diseases.
The Inflammation of Aging – ‘Inflammaging’
Macrophages, essential white blood cells crucial for our immune systems and overall well-being, perform vital functions such as engulfing dead or dying cells to facilitate the removal of cellular debris and patrolling our bodies for foreign invaders and pathogens. Additionally, they act as vigilant guardians for our immune systems, calling for assistance from other immune cells whenever necessary.
As researchers have observed that macrophages become less efficient as we age, the exact reasons behind this decline have remained elusive. However, Desai and his team's recent breakthrough sheds light on this matter.
Through their research, Desai and his team have identified a fundamental mechanism, akin to a "keystone," responsible for the age-related changes in macrophages. These changes render the macrophages susceptible to chronic, low-grade inflammation even under normal conditions. Furthermore, when these immune cells encounter an invader or tissue damage, they can become overly active, leading to a phenomenon known as "inflammaging" – a state of persistent inflammation that contributes to the aging process.
Moreover, the researchers from UVA Health believe that the mechanism they have uncovered is likely not limited to macrophages alone but may apply to numerous other immune cells that originate in the bone marrow. This exciting prospect suggests that we could potentially enhance the proper functioning of these related immune cells too, offering our immune systems a substantial boost as we age and become more vulnerable to various diseases. By targeting this mechanism, there is hope for bolstering our immune defenses in old age and improving our ability to fend off illnesses effectively.
Next Steps
Addressing "inflammaging" is not as straightforward as merely taking a calcium supplement since the issue lies not in calcium deficiency but in the macrophages' impaired ability to utilize it effectively. Nonetheless, Desai's recent breakthrough has successfully identified the specific molecular machinery involved in this process. As a result, there is hope that we can explore methods to stimulate this machinery in aging cells.
Desai acknowledges the collaborative nature of this research, which spans across computational biology, immunology, cell biology, and biophysics. He highlights the determination of Phil Seegren, the graduate student who played a pivotal role in spearheading this ambitious project. Looking ahead, a similarly ambitious effort is required to decipher the intricate regulatory mechanisms controlling this mitochondrial process in various types of macrophages. Subsequently, by creatively manipulating this regulation, we can expect significant biomedical implications and potential advances in the field.
Aging Findings Published
The researchers have published their findings in the scientific journal Nature Aging. The article is open access, meaning it is free to read.
The research team consisted of Seegren, Logan R. Harper, Taylor K. Downs, Xiao-Yu Zhao, Shivapriya B. Viswanathan, Marta E. Stremska, Rachel J. Olson, Joel Kennedy, Sarah E. Ewald, Pankaj Kumar and Desai. The scientists reported that they have no financial interests in the work.
The research was supported by the National Institutes of Health, grants AI155808, GM108989, GM138381, P30 CA044579 and T32 GM007055-46, and by the Owens Family Foundation.
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