Researchers at the University of Virginia School of Medicine have found that dysfunctional calcium regulation in certain immune cells’ mitochondria leads to persistent inflammation which in turn speeds up aging. They suggest that boosting calcium absorption in these cells could help decelerate age-associated diseases. The research has been published in the scientific journal, Nature Aging.
The scientific team has identified a principal factor causing persistent inflammation that fast-tracks aging. This discovery could pave the way to extend our lifespan, enhance our health, and help prevent age-related diseases like fatal cardiovascular diseases and debilitating neurocognitive disorders that impair our mental faculties.
The culprit behind this damaging inflammation is dysfunctional calcium signaling within the mitochondria of certain immune cells. Mitochondria, serving as the powerhouse of all cells, heavily rely on calcium signaling.
Implications of the Findings
The research team, led by Bimal N. Desai, PhD, at UVA Health, discovered that as they age, the mitochondria in macrophages, a type of immune cell, lose their capability to intake and utilize calcium. This defect leads to persistent inflammation that’s responsible for many health issues linked to old age.
Desai and his colleagues have identified a key initiator for “inflammaging” – inflammation that drives aging. They suggest that increasing calcium uptake by these mitochondrial macrophages could prevent this detrimental inflammation and its serious outcomes. Considering that macrophages are found in all body organs, including the brain, focusing targeted drugs on these “tissue-resident macrophages” might allow us to slow down age-related neurodegenerative diseases.
“I believe we have made a crucial conceptual breakthrough in understanding the molecular basis of age-associated inflammation,” said Desai, from UVA’s Department of Pharmacology and UVA’s Carter Immunology Center. “This discovery sheds light on new therapeutic strategies to block the inflammatory processes at the core of many cardiometabolic and neurodegenerative diseases.”
The Aging Inflammation – ‘Inflammaging’
Macrophages are white blood cells with critical roles in our immune systems and consequently, our overall health. They consume dead or dying cells, assisting our bodies in cellular debris removal, and they scout for pathogens and other foreign invaders, acting as vital sentinels for our immune systems.
The decline in effectiveness of macrophages with age was a known fact, but the reasons behind this were formerly uncertain. Desai’s latest discovery provides some clarity.
A Central Mechanism in Aging
Desai and his team’s research have revealed a central mechanism responsible for age-related changes in macrophages. These changes, the researchers believe, predispose the macrophages to chronic, mild inflammation, and they become hyperactive when faced with an invader or tissue damage. This results in “inflammaging” – chronic inflammation that drives aging.
Moreover, the scientists at UVA Health anticipate that this mechanism will also apply to many other related immune cells produced in the bone marrow. This implies that we may be able to invigorate the proper functioning of these cells, providing our immune systems with a significant boost in old age when we are more vulnerable to disease.
The Path Forward
Mitigating “inflammaging” is not as simple as consuming a calcium supplement. The problem lies more in the macrophages’ inability to effectively use calcium. However, Desai’s recent discovery has identified the precise molecular machinery implicated in this process, so we should be able to devise ways to stimulate this machinery in aging cells.
“Such an interdisciplinary research effort that intersects computational biology, immunology, cell biology, and biophysics would not have been feasible without the determination of Phil Seegren, the graduate student who led this ambitious project,” Desai stated. “Moving forward, we need an equally ambitious effort to decipher the wiring that controls this mitochondrial process in different types of macrophages and creatively manipulate that wiring for biomedical impact.”
Publication of Aging Findings
The researchers have disseminated their findings in the scientific journal Nature Aging. The article is available free of charge for reading.
Reference: “Reduced mitochondrial calcium uptake in macrophages is a major driver of inflammaging” by Philip V. Seegren et al., 5 June 2023, Nature Aging.
DOI: 10.1038/s43587-023-00436-8
The research team included 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 disclosed no financial interests in the work.
The research was funded by the National Institutes of Health, grants AI155808, GM108989, GM138381, P30 CA044579 and T32 GM007055-46, and by the Owens Family Foundation.
Table of Contents
Frequently Asked Questions (FAQs) about Calcium Uptake in Aging
What is the key finding of the research conducted by the team at the University of Virginia School of Medicine?
The team found that improper calcium signaling in the mitochondria of certain immune cells contributes to chronic inflammation that accelerates aging. They suggest that enhancing calcium uptake in these cells could slow down age-related diseases.
Who led the research team at UVA Health?
The research team at UVA Health was led by Bimal N. Desai, PhD.
What are the potential benefits of enhancing calcium uptake in mitochondrial macrophages?
Enhancing calcium uptake in these cells could deter harmful inflammation and its severe consequences. It might also help slow down age-related neurodegenerative diseases as macrophages are present in all body organs, including the brain.
What is ‘inflammaging’?
‘Inflammaging’ is a term coined to describe chronic inflammation that drives aging.
What is the solution proposed by the researchers for ‘inflammaging’?
The researchers suggest that the solution is not as simple as taking a calcium supplement. Rather, the issue lies in the macrophages’ inability to properly utilize calcium. They suggest stimulating the precise molecular machinery involved in this process in aging cells.
Where has the research been published?
The research has been published in the scientific journal, Nature Aging.
Who funded the research?
The research was funded by the National Institutes of Health and the Owens Family Foundation.
More about Calcium Uptake in Aging
- University of Virginia School of Medicine
- Nature Aging Journal
- National Institutes of Health (NIH)
- UVA’s Department of Pharmacology
- UVA’s Carter Immunology Center
- Information on Mitochondria
- Information on Macrophages
5 comments
wow, this is amazing! Who’d have thot calcium was so important for our aging. Hope they can figure out how to enhance it, would love to see this kind of breakthrough in my lifetime.
This is fantastic. I’ve always wondered why we age and this gives a bit of insight. Can’t wait to hear more about this research.
im so impressed with these scientists! to think they could potentially slow down aging, what a time to be alive!
I must say I’m surprised. I knew calcium was good for the bones but didn’t know it was crucial for the immune cells too. great job UVA!
Brilliant work from Desai and team. Looking forward to seeing where this leads. Could be a game changer for age-related diseases.