Priority Research Paper Volume 11, Issue 21 pp 9234—9263
Age-associated changes in human CD4+ T cells point to mitochondrial dysfunction consequent to impaired autophagy
- 1 Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
- 2 Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
- 3 Flow Cytometry Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
- 4 Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
- 5 Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
- 6 Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY 10461, USA
- 7 Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Received: August 24, 2019 Accepted: October 29, 2019 Published: November 9, 2019https://doi.org/10.18632/aging.102438
How to Cite
Copyright © 2019 Bektas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
To gain understanding on the mechanisms that drive immunosenescence in humans, we examined CD4+ T cells obtained from younger (20-39 years-old) and older (70+ years-old) healthy participants of the Baltimore Longitudinal Study on Aging (BLSA). We found that mitochondrial proteins involved in the electron transport chain were overrepresented in cells from older participants, with prevalent dysregulation of oxidative phosphorylation and energy metabolism molecular pathways. Surprisingly, gene transcripts coding for mitochondrial proteins pertaining to oxidative phosphorylation and electron transport chain pathways were underrepresented in older individuals. Paralleling the observed decrease in gene expression, mitochondrial respiration was impaired in CD4+ T cells from older subjects. Though mitochondrial number in both naïve and memory cells visualized with electron microcopy was similar in older versus younger participants, there were a significantly higher number of autophagosomes, many of them containing undegraded mitochondria, in older individuals. The presence of mitochondria inside the accumulated autophagic compartments in CD4+ T cells from older individuals was confirmed by immunofluorescence. These findings suggest that older age is associated with persistence of dysfunctional mitochondria in CD4+ T lymphocytes caused by defective mitochondrial turnover by autophagy, which may trigger chronic inflammation and contribute to the impairment of immune defense in older persons.