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Aging impairs mitochondrial respiratory capacity in classical monocytes
Open accessAbstract
Aging is a critical healthcare concern, with age-related inflammation disposing individuals to a variety of diseases. Monocytes are affected by the aging process, with increased inflammation and impaired cellular functions such as phagocytosis. Mechanisms by which aging alters monocyte function are unknown, but recent research suggests that the balance of metabolic processes determine immune cell phenotype and function. Given the known association between aging and mitochondrial dysfunction in other tissues, we hypothesized that aging would impair mitochondrial function in monocytes. To test this, we isolated classical monocytes from young and older adults and tested mitochondrial function by a Seahorse assay. Aging reduced mitochondrial respiratory capacity and spare capacity in monocytes. Mitochondrial dysfunction is a potential mechanism by which aging alters monocyte phenotype and may impair inflammatory functions, especially in low-glucose environments where oxidative metabolism is necessary to meet energy demands.
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“It has been observed that respiratory capacity steadily declines with age in CD14 + monocytes as a consequence of mitochondrial dysfunction (144).”
From The impact of ageing on monocytes and macrophages (2021) · cites this paper as [144]
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Pence, B. D. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.5ce0920-613r · Cited by 9
Giacomello, G., Otto, C., Priller, J., Ruprecht, K., Böttcher, C., & Parr, M. K. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45010051 · Cited by 8
Interaction of aging and Immunosenescence: New therapeutic targets of aging
Liao, S., Ning, Q., Chen, Y., Zhao, X., & Tang, S. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109397 · Cited by 8
Distinct mitochondrial respiration profiles in pediatric patients with febrile illness versus sepsis
Sartori, L. F., Tsemberis, E., Hernandez, T., Luchette, K., Zhang, D. “., Farooqi, S., Bush, J., McCann, J., Balamuth, F., & Weiss, S. L. (2024) · Pediatric Research · doi:10.1038/s41390-024-03420-z · Cited by 7
Aging and monocyte immunometabolism in COVID-19
Pence, B. D. (2021) · Aging · doi:10.18632/aging.202918 · Cited by 7
Immunometabolic insights into women's health across all ages
Matos-Silva, M., Lira, F. S., & Antunes, B. M. (2025) · Maturitas · doi:10.1016/j.maturitas.2025.108719 · Cited by 6
Emerging frontiers in the mitochondrial regulation of dendritic cell biology
Chen, B., & Mayer, J. U. (2026) · Redox Biology · doi:10.1016/j.redox.2026.104032 · Cited by 7
“In human monocytes it has been shown that the mitochondrial respiratory capacity is significantly impaired and reduced by almost half, suggesting reduced mitochondrial fitness [110].”
Childers, G. M., & Harry, G. J. (2021) · Neuromethods · doi:10.1007/978-1-0716-1637-6_14 · Cited by 6
Moratilla, A., Martín, D., Cadenas-Martín, M., Stokking, M., Simón, M. A. Q., Arnalich‐Montiel, F., & Miguel, M. P. D. (2024) · Cells · doi:10.3390/cells13110971 · Cited by 5
“Monocytes obtain energy by both oxidative phosphorylation and glycolysis, whereas lymphocytes obtain energy only through oxidative phosphorylation [59,60].”
BackgroundGao, Q., Yang, L., Teng, F., & Guo, S. (2023) · BMC Emergency Medicine · doi:10.1186/s12873-023-00779-w · Cited by 7
“Aging increases the proportion of CD14 + CD16 + + monocytes in the circulation [13].”
BackgroundGrant, C., Duffin, E., O’Connell, F., Nadarajan, P., Bergin, C. J., Keane, J., & O’Sullivan, M. P. (2025) · Immunology · doi:10.1111/imm.13922 · Cited by 5
Renal inflammaging: Mechanisms, pathophysiology and therapeutic prospects
Yan, J., Zhao, F., Zhang, R., Wu, H., Lyu, J., Shi, L., & Wang, H. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103098 · Cited by 5
Aging mitochondria in the context of SARS-CoV-2: exploring interactions and implications
Delpino, M. V., & Quarleri, J. F. (2024) · Frontiers in Aging · doi:10.3389/fragi.2024.1442323 · Cited by 5
“The aging process impacts monocytes ’ mitochondrial functions, leading to heightened in fl ammation and compromised cellular functions, including phagocytosis (Pence and Yarbro, 2018).”
BackgroundCumming, B. M., Addicott, K. W., Maruri, F., Pillay, V., Asmal, R., Moodley, S., Barreto-Durate, B., Araújo‐Pereira, M., Mazibuko, M., Mhlane, Z., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1465448 · Cited by 5
Blood Cell Mitochondrial Respiration Increases With Age and Varies by Sex in Healthy Adults
Phang, H. J., Bergstrom, J., Keri, B., Heimler, S., Dozier, S., Scandalis, L., Wing, D., Moreno, D. S.-M., Sun, N., & Molina, A. J. A. (2026) · Aging Cell · doi:10.1111/acel.70387 · Cited by 5
“For example, a study by Pence and Yarbro included CD16 depletion for isolation of classical monocytes (CD14 + CD16 − ) without intermediate (CD14 + CD16+) or non-classical (CD14 dim CD16+) monocytes, resulting in removal of about 25% of monocytes from the population (Pence and Yarbro 2018).”
Non-Invasive Cancer Detection Using Blood Test and Predictive Modeling Approach
Tarawneh, A. S., Omari, A. A., Al-khlifeh, E., Tarawneh, F., Alghamdi, M., Alrowaily, M. A., Alkhazi, I. S., & Hassanat, A. B. A. (2025) · Advances and Applications in Bioinformatics and Chemistry · doi:10.2147/aabc.s488604 · Cited by 4
“46 Research conducted on the Jordanian population indicates that age has a fluctuating impact on the occurrence of cancer.”
Zapalenie starcze - mechanizmy i szlaki sygnałowe
Grabowska, K., Nowacka-Chmielewska, M. M., Barski, J. J., & Liśkiewicz, D. (2021) · Postępy Biochemii · doi:10.18388/pb.2021_375 · Cited by 4
Behrmann, A., Zhong, D., Li, L., Xie, S., Mead, M., Sabaeifard, P., Goodarzi, M., Lemoff, A. S., Kozlitina, J., & Towler, D. A. (2023) · Endocrinology · doi:10.1210/endocr/bqad192 · Cited by 3
Wells, L., Yang, Q., Iorio, C., Peragerasingam, M., Campbell, Z. E., Ng, A. C.-H., Reeks, C., Yee, S., & Screaton, R. A. (2026) · Diabetologia · doi:10.1007/s00125-026-06728-z · Cited by 1
“As loss of SRC is a hallmark of ageing cells [20], the lower SRC setpoint in male islets may, in part, explain the preferential loss of insulin secretion in human male populations [56, 57], and suggest that beta cells in male individuals may be more susceptible to genetic or environmental triggers…”
A Biomaterial Model to Assess the Effects of Age in Vascularization
Silberman, J., Boehlein, J., Abbate, T., & Moore, E. (2022) · Cells Tissues Organs · doi:10.1159/000523859 · Cited by 4
“…the effects of age on functions of the innate immune system such as reduced phagocytosis, altered phenotype, and reduced cytokine production which all contribute to the loss of functionality in aging [Hearps et al., 2012; Albright et al., 2016; Hall et al., 2016; Pence and Yarbro, 2018].”
BackgroundGao, Q., Yang, L., Teng, F., Cheng, X., & Guo, S. (2022) · Experimental Gerontology · doi:10.1016/j.exger.2022.112012 · Cited by 3
“, 2011) and the proportion of CD14++CD16− monocytes in older adults is reduced compared with that in younger adults (Pence and Yarbro, 2018).”
From Genesis to Old Age: Exploring the Immune System One Cell at a Time with Flow Cytometry
Larbi, A. (2024) · Biomedicines · doi:10.3390/biomedicines12071469 · Cited by 4
The aging transplant population and immunobiology: any therapeutic implication?
Schaenman, J. M. D., & Goldwater, D. S. (2020) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0000000000000760 · Cited by 3
“Older kidney transplant recipients demonstrate alterations in monocyte differentiation and decreased expression of Toll-like receptor 4 (TLR4) in older as compared with younger patients, possibly related to defects in mitochondrial respiration associated with aging [39,40].”
BackgroundSenescent macrophages alter fibroblast fibrogenesis in response to SARS-CoV-2 infection
Pence, B. D., Zhang, Y., Antwi, I., & Cory, T. J. (2022) · NeuroImmune Pharmacology and Therapeutics · doi:10.1515/nipt-2022-0003 · Cited by 2
“This procedure results in a highly pure (>90%) population of classical monocytes [27].”
BackgroundZhao, Y., Ou, M., Hao, X., & Zhu, T. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e28137 · Cited by 2
“For another, previous study reported that aging impairs mitochondrial respiration in classical monocytes by reducing MR and SRC [37].”
BackgroundPolygenic Profile and Magnitude Impact of Inflammatory Response in Soccer Athletes
Kanope, T., dos Santos, C. G. M., Veneroso, C. E., Fornazieiro, A., de Assis, M. G., & Pimenta, E. M. (2024) · Open Journal of Genetics · doi:10.4236/ojgen.2024.143005 · Cited by 3
Recent developments and future perspectives in aging and macrophage immunometabolism
Pence, B. D. (2021) · AIMS molecular science · doi:10.3934/molsci.2021015 · Cited by 3
“This may be true for monocytes as well, as aging increases proportions of intermediate and non-classical monocytes in circulation [23,47].”
BackgroundMethodGrowth differentiation factor-15 is associated with age-related monocyte immunosenescencePreprint
Pence, B. D., Yarbro, J. R., & Emmons, R. S. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.02.05.935643 · Cited by 2
“For monocyte phenotype determination, 100 μl whole blood was stained with anti-CD14-PE and anti-CD16-Brilliant Violet 421 antibodies and analyzed on an Attune NxT flow cytometer as previously described [5].”
BackgroundMethodResultInfluentialTorres, A., Marchioro, S. B., Ribeiro, M. B., de Morais, I. R. B., Freire, S. M., & Nascimento, R. J. M. (2021) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.2021039675 · Cited by 2
Valencia, A. P., Pharaoh, G. A., Brandao, A. F., & Marcinek, D. J. (2024) · Journal of Visualized Experiments · doi:10.3791/66863 · Cited by 1
Effect of Lead on the Bioenergetics of the Isolated Human Monocytes
Omar, U. M., & Elmorsy, E. M. (2022) · Pakistan Journal of Medical and Health Sciences · doi:10.53350/pjmhs22162603 · Cited by 1
Au cœur de la capacité de vitalité : l’immuno-métabolisme et sa nature holistique
Mercier, J., Colson, S. S., & Rousseau, A. (2024) · Cahiers de Nutrition et de Diététique · doi:10.1016/j.cnd.2024.04.002 · Cited by 2
Pearson, A. G., Zawari, M., Pearson, J. F., & Hampton, M. B. (2020) · Free Radical Research · doi:10.1080/10715762.2020.1753722 · Cited by 1
Combination nanoadjuvant-based vaccine against influenza virus for older adults
Senapati, S. (2020) · doi:10.31274/etd-20210114-134 · Cited by 1
Metadata
- Authors
- Pence, B. D., & Yarbro, J. R.
- Affiliations
- University of Memphis (US)
- Corresponding author
- Pence, Brandt D.
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 108
- Pages
- 112-117
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W2798053566
- Cited by
- 120
- References
- 40
- Citations by year
- 2026: 11 · 2025: 8 · 2024: 19 · 2023: 11 · 2022: 17 · 2021: 21 · 2020: 18 · 2019: 10 · 2018: 5
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Experimental Gerontology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- University of Memphis
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- aging, classical monocytes, mitochondrial respiratory capacity, mitochondrial dysfunction, spare respiratory capacity, age-related inflammation, monocyte phenotype, oxidative metabolism, glucose metabolism, immune cell function
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Female, Flow Cytometry, Humans, Immunity, Innate, Inflammation, Male, Middle Aged, Mitochondria, Monocytes, Phagocytosis, Cell Respiration, Young Adult
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