Senescent T-lymphocytes are antigen-experienced cells that express the killer-cell lectin-like receptor G1 (KLRG1) and/or CD57; fail to clonally expand following further antigenic stimulation and prevail in the resting blood of older adults compared to the young. Physical exercise mobilises T-lymphocytes into the bloodstream and is therefore a model with which to compare age-related phenotypes of blood-resident T-cells with those T-cells entering the blood from peripheral lymphoid compartments. Eight young (Y; Age: 21+/-3 years) and 8 older (O; Age: 56+/-3 years) healthy males completed a maximal treadmill exercise protocol. Blood lymphocytes isolated before, immediately after and 1h after exercise were assessed for cell surface expression of KLRG1, CD57, CD28, CD45RA, CD45RO, CD62L and lymphocyte subset markers using three-colour flow cytometry. Lymphocyte subset numbers (CD3+, CD3+/CD4+, CD3+/CD8 and CD3-/CD56+) increased with exercise (p<0.05) but were not different between Y and O. At rest and immediately after exercise, the percentage of CD3+/CD8+ T-lymphocytes expressing KLRG1 and CD45RO was greater in O than Y, whereas Y had a greater expression of CD45RA and CD62L than O. The percentage of all CD3+/CD8+ and CD3+/CD4+ T-lymphocytes expressing KLRG1 and CD57 increased after exercise, but the magnitude of change was not age-dependent. In conclusion, there is a greater proportion of senescent CD3+/CD8+ T-lymphocytes in the blood of older adults compared to young at rest and immediately after exhaustive exercise, indicating that the greater frequency of KLRG1+/CD8+ T-lymphocytes in older humans is ubiquitous and not localised to the peripheral blood.
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http://dx.doi.org/10.1016/j.bbi.2007.11.002 | DOI Listing |
AIDS Res Hum Retroviruses
December 2024
Department of Immunobiology, College of Medicine, University of Arizona, Tucson, Arizona, USA.
Despite advancements in antiretroviral therapy (ART) that reduces the viral load to undetectable levels and improve CD4 T cell counts, viral eradication has not been achieved due to HIV-1 persistence in resting CD4 T-cells. We, therefore, characterized the gene, which is essential for HIV-1 replication and pathogenesis, from 20 virologically controlled aging individuals with HIV (HIV) on long-term ART and improved CD4 T-cell counts, with a particular focus on older individuals. Peripheral blood mononuclear cell genomic DNA from HIV were used to amplify gene by polymerase chain reaction followed by nucleotide sequencing and analysis.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Age-associated differences in the effect of repetitive vaccination, particularly on memory T-cell and B-cell responses, remain unclear. While older adults (aged ≥65 years) exhibited enhanced IgG responses following COVID-19 mRNA booster vaccination, they produced fewer spike-specific circulating follicular helper T cells-1 than younger adults. Similarly, the cytotoxic CD8 T-cell response remained diminished with reduced PD-1 expression even after booster vaccination compared with that in younger adults, suggesting impaired memory T-cell activation in older adults.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
Division of Molecular Carcinogenesis, Oncode Institute, The Netherlands Cancer Institute, Amsterdam 1066 CX, The Netherlands.
Drugs that eliminate senescent cells, senolytics, can be powerful when combined with prosenescence cancer therapies. Using a CRISPR/Cas9-based genetic screen, we identify here SLC25A23 as a vulnerability of senescent cancer cells. Suppressing SLC25A23 disrupts cellular calcium homeostasis, impairs oxidative phosphorylation, and interferes with redox signaling, leading to death of senescent cells.
View Article and Find Full Text PDFImmun Inflamm Dis
December 2024
Department of Dermatology, The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital), Changsha, China.
Background: Rosacea is a common inflammatory skin disorder characterized by frequent facial flushing, erythema, telangiectasia, and papules, with a higher incidence observed in individuals aged 30-50 years and a tendency to decrease in the elderly. This age-related decline in incidence drew our attention to further explore the relationship between rosacea pathogenesis and aging.
Methods: We analyzed the incidence of rosacea across 8340 individuals without systemic diseases.
Int J Mol Sci
November 2024
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Malignant tumors can evade immune surveillance and elimination through multiple mechanisms, with the induction of immune cell dysfunction serving as a crucial strategy. Mounting evidence indicates that T cell senescence constitutes the primary mechanism underlying T cell dysfunction in acute myeloid leukemia (AML) and represents one of the potential causes of immunotherapy failure. AML usually progresses rapidly and is highly susceptible to drug resistance, thereby resulting in recurrence and patient mortality.
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