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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Respiratory capacity in CD14+ monocytes declines steadily with age because of mitochondrial dysfunction.
“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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Effects of cellular senescence on metabolic pathways in non-immune and immune cells
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“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript Abbreviations AMP adenosine monophosphate AMPK AMP-activated protein kinase ADP adenosine diphosphate ATP adenosine triphosphate BCR B cell receptor DN Double negative ECAR extracellular acidification rate EGF epithelium growth factor FA f…”
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Metformin Suppresses Monocyte Immunometabolic Activation by SARS-CoV-2 Spike Protein Subunit 1
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“As we have previously described (46), this procedure results in a highly pure (> 85%) population of classical monocytes, with depletion of intermediate and non-classical monocytes due to the presence of an anti-CD16 antibody in the cocktail.”
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“In our examination of monocyte subset proportions defined by CD14 and CD16 expression, we observed a significant increase in the proportion of nonclassical (CD14dimCD16+) monocytes in elderly controls relative to adults, which has been observed by others (Hearps et al., 2012; Nyugen et al., 2010; Pence and Yarbro, 201…”
Roth‐Walter, F., Adcock, I. M., Benito‐Villalvilla, C., Bianchini, R., Bjermer, L. H., Caramori, G., Cari, L., Chung, K. F., Diamant, Z., Eguíluz‐Gracia, I., et al. (2023) · Allergy · doi:10.1111/all.15977 · Cited by 31 · see citing works
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Trained Immunity Enhances Human Monocyte Function in Aging and Sepsis
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“Decreases in respiration and glycolysis have been linked to declining immune systems in aging individuals (27, 30, 31).”
BackgroundThe aging of ER-mitochondria communication: A journey from undifferentiated to aged cells
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BackgroundInfluentialMeta‐inflammaging at the crossroad of geroscience
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Senescence in Monocytes Facilitates Dengue Virus Infection by Increasing Infectivity
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“Through the immune profiling of isolated classical monocytes from younger and older adults, the number of circulating classical monocytes is reduced in the older population, while intermediate and non-classical monocytes are increased with age (Pence and Yarbro, 2018).”
BackgroundHealthy and premature aging of monocytes and macrophages
Basu, S., Ulbricht, Y., & Rossol, M. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1506165 · Cited by 26 · see citing works
“Pence and Yarbro also reported impaired mitochondrial respiratory activity in classical monocytes from old individuals using fl ow cytometry (120).”
Aging Leukocytes and the Inflammatory Microenvironment of the Adipose Tissue
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“Mitochondrial dysfunction, such as bioenergetic function, altered mitochondrial gene expression, and membrane potential in monocytes, is implicated in various human diseases, including kidney diseases [69,70], aging [71], metabolic disorders, atherosclerosis [70], and infections [72,73].”
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Immune Cells and Immunosenescence
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“For example, one study reported reduced reserve capacity in monocytes among older adults compared to younger adults [32].”
Alterations in metabolic pathways: a bridge between aging and weaker innate immune response
Saleh, Z., Mirzazadeh, S., Mirzaei, F., Heidarnejad, K., Meri, S., & Kalantar, K. (2024) · Frontiers in Aging · doi:10.3389/fragi.2024.1358330 · Cited by 16 · see citing works
“Damaged mitochondria or increased activity of NADPH oxidase could be the deriver of elevation in ROS level (Pence and Yarbro, 2018; Saare et al., 2020).”
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The immunometabolic roots of aging
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Transcriptional characteristics and functional validation of three monocyte subsets during aging
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“However, these functions in monocytes from older adults are impaired on account of the cellular energy shortage [18, 31].”
BackgroundGrowth differentiation factor‐15 is associated with age‐related monocyte dysfunction
Pence, B. D., Yarbro, J. R., & Emmons, R. S. (2020) · Aging Medicine · doi:10.1002/agm2.12128 · Cited by 15 · see citing works
Pantoja, P. D. S., Schmitt, B. L., Maurmann, R. M., & Pence, B. D. (2025) · Molecules · doi:10.3390/molecules30051178 · Cited by 14 · see citing works
“In addition, recent studies have also evidenced an association between defects in cellular metabolic processes and changes in immune function, as demonstrated by the co-occurrence of mitochondrial respiration impairment and abrogated monocyte LPS response in older adults [28,29].”
Dobbs, K. R., Embury, P., Koech, E., Ogolla, S., Munga, S., Kazura, J. W., & Dent, A. E. (2021) · Immunity & Ageing · doi:10.1186/s12979-021-00223-2 · Cited by 13 · see citing works
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Dysregulated cytokine and oxidative response in hyper-glycolytic monocytes in obesity
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“In macrophages, aging impairs ETC function and OXPHOS capacity, and is accompanied by a reduction in mitochondrial spare respiratory capacity (103, 104).”
FoxO1 Controls Redox Regulation and Cellular Physiology of BV-2 Microglial Cells
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“Notably, it was reported that aged monocytes exhibit a dramatic reduction in maximal oxygen consumption capacity, without alteration of basal respiration [29].”
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“It should be noted that the prevalence of both diseases increases with age (49, 50), while ageing impairs mitochondrial reserve capacity of monocytes (51).”
BackgroundMitochondrial dysfunction at the cornerstone of inflammatory exacerbation in aged macrophages
Maurmann, R. M., Schmitt, B. L., Mosalmanzadeh, N., & Pence, B. D. (2023) · Exploration of Immunology · doi:10.37349/ei.2023.00112 · Cited by 10 · see citing works
Noh, J. Y., Han, H. W., Kim, D. M., Giles, E. D., Farnell, Y. Z., Wright, G. A., & Sun, Y. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1357444 · Cited by 11 · see citing works
“It has been shown that aging impacts the programming of innate immune cells and contributes to in fl ammaging and age-associated diseases (20 – 22).”
BackgroundFanning the Flames of Inflammaging: Impact of Monocyte Metabolic Reprogramming
Pence, B. D. (2020) · Immunometabolism · doi:10.20900/immunometab20200025 · Cited by 10 · see citing works
“Of note, recent evidence suggests that non-classical monocytes exhibit hallmarks of senescence, including both mitochondrial dysfunction and increased SASP production [13], and non-classical monocyte proportions in the circulation are increased during aging [5,7].”
BackgroundResultInfluentialPena, G. S., Callow, D. D., Evans, W. S., Prior, S. J., & Smith, J. C. (2022) · Experimental Gerontology · doi:10.1016/j.exger.2022.111973 · Cited by 8 · see citing works
Atypical monocytes in COVID-19: Lighting the fire of cytokine storm?
Pence, B. D. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.5ce0920-613r · Cited by 9 · see citing works
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 · see citing works
Interaction of aging and Immunosenescence: New therapeutic targets of aging
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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 · see citing works
Aging and monocyte immunometabolism in COVID-19
Pence, B. D. (2021) · Aging · doi:10.18632/aging.202918 · Cited by 7 · see citing works
Immunometabolic insights into women's health across all ages
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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 · see citing works
“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].”
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“Monocytes obtain energy by both oxidative phosphorylation and glycolysis, whereas lymphocytes obtain energy only through oxidative phosphorylation [59,60].”
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“Aging increases the proportion of CD14 + CD16 + + monocytes in the circulation [13].”
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Renal inflammaging: Mechanisms, pathophysiology and therapeutic prospects
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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 · see citing works
“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 · see citing works
Blood Cell Mitochondrial Respiration Increases With Age and Varies by Sex in Healthy Adults
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“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 · see citing works
“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
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“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
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“…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].”
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“, 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
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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 · see citing works
“This procedure results in a highly pure (>90%) population of classical monocytes [27].”
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“For another, previous study reported that aging impairs mitochondrial respiration in classical monocytes by reducing MR and SRC [37].”
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Recent developments and future perspectives in aging and macrophage immunometabolism
Pence, B. D. (2021) · AIMS molecular science · doi:10.3934/molsci.2021015 · Cited by 2 · see citing works
“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
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“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].”
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Effect of Lead on the Bioenergetics of the Isolated Human Monocytes
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Au cœur de la capacité de vitalité : l’immuno-métabolisme et sa nature holistique
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- 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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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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