Molecular and biochemical pathways of apoptosis in lymphocytes from aged humans.
In this study, we investigated a role of apoptosis in lymphopenia and progressive cell-mediated immunodeficiency associated with aging. We examined two major signaling pathways of apoptosis in lymphocytes from aged humans and compared them with lymphocytes from young subjects. Both CD4+ and CD8+ T cell subsets from aged subjects demonstrated increased sensitivity to TNFR-mediated and Fas-mediated apoptosis that was associated with overexpression of death receptors and adapter molecules associated with death signaling. An increased expression and activity of both initiator (caspase 8) and effector (caspase 3) caspases was observed in lymphocytes from aged subjects as compared to young individuals. Furthermore, an increased expression of Bax and decreased expression of Bcl-2 (both at the protein and mRNA level) was found in lymphocytes from aged subjects. These data suggest that increased sensitivity of lymphocytes from aged subjects to death signals may play an important role in the pathogenesis of lymphopenia and T cell deficiency associated with the aging process.
Gupta
S
S
Laboratory of Molecular Immunology, Division of Basic and Clinical Immunology, University of California, Irvine, CA 92697-4069, USA. sgupta@uci.edu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology* / Q000473:pathology* / Q000502:physiology; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology* / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D053222:Fas Ligand Protein; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases