Abstract
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.
Highlights
Human aging is characterized by increased susceptibility to diseases and impaired capacity to handle stress and challenges from the environment, leading to excess morbidity and mortality [1, 2]
In quantitative discovery proteomics of cytoplasmic extracts, we found that proteins related to oxidative phosphorylation and integration of energy metabolism were overrepresented in CD4+ T cells from older compared to younger individuals
From previous studies, we performed a discovery proteomic analysis on cytoplasmic extract because our prior findings suggested that the origin of the proinflammatory state of aging in CD4+ T lymphocytes was metabolic in nature [30]
Summary
Human aging is characterized by increased susceptibility to diseases and impaired capacity to handle stress and challenges from the environment, leading to excess morbidity and mortality [1, 2]. A critical factor in this process is a progressive decline of immunity, which results in reduced protection against external microorganismal threats, diminished surveillance and reduced repair capacity of damaged cells www.aging-us.com and tissues that can lead to degenerative diseases. Inflammaging is characterized by a robust increase with aging of blood levels of proinflammatory markers, and is a strong risk factor for the occurrence, progression, and complication of many chronic diseases, including cardiovascular and neurodegenerative diseases [7, 8]. Several aspects of the immune response are affected by aging, including proper initiation and, especially, maintenance and cessation [6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
