Accelerated Aging of Immune Cells Linked to Exhaustion of Immune Response in Patients with AIDS; Telomere Research Suggests Role of Cell Senescence in HIV Disease Process.MENLO PARK, Calif.--(BUSINESS WIRE)--June 27, 1996--Research focused on a key marker of cell replication demonstrates that the immune cells of HIV-infected patients age at an accelerated rate, suggesting an explanation for the eventual breakdown of the immune response immune response n. An integrated bodily response to an antigen, especially one mediated by lymphocytes and involving recognition of antigens by specific antibodies or previously sensitized lymphocytes. in AIDS. The findings, published today in the journal AIDS by scientists from Geron Corporation and UCLA UCLA University of California at Los Angeles UCLA University Center for Learning Assistance (Illinois State University) UCLA University of Carrollton, TX and Lower Addison, TX School of Medicine, are the first to suggest a role for cell aging, or senescence senescence /se·nes·cence/ (se-nes´ens) the process of growing old, especially the condition resulting from the transitions and accumulations of the deleterious aging processes. se·nes·cence n. , in the HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. disease process. In this study, the researchers examined the immune cells of patients with late-stage HIV and found that these cells had apparently aged to a level similar to those of a normal 100-year-old person. This finding provides evidence that increased rounds of immune cell division occur during chronic HIV disease, suggesting that the virus remains active for years, stimulating an aggressive immune response that is eventually exhausted. "These results may provide an answer to the unsolved mystery of why HIV initially causes a flu-like sickness that goes away, only to return some 10 years later with deadly effects," said Michael D. West Dr. Michael D. West is an entrepreneurial scientist and visionary [1] [2] [3] [4] who has led progress in anti-aging and biotechnology. He is CEO of BioTime, Inc. , Ph.D., Geron vice president for new technologies and one of the authors of the study. "It now appears that the immune system immune system Cells, cell products, organs, and structures of the body involved in the detection and destruction of foreign invaders, such as bacteria, viruses, and cancer cells. Immunity is based on the system's ability to launch a defense against such invaders. is working overtime during all those years to contain the virus, resulting in the premature aging of certain immune cells." The study focused on telomere telomere /telo·mere/ (tel´o-mer) an extremity of a chromosome, which has specific properties, one of which is a polarity that prevents reunion with any fragment after a chromosome has been broken. length as a marker of replicative aging in CD8 cells CD8 cells T cells with CD8 on the surface, which are immunosuppressive and suppress mitogen-induced and antigen-specific antibody production, and require CD4 cell cooperation , a subset of immune cells known as cytotoxic T-cells which kill virus-infected cells. Previous research by Geron and its scientific collaborators has shown that the aging process of cells may be controlled by a molecular "clock" consisting of telomeres. Telomeres are repeated DNA sequences found at the ends of chromosomes that serve to organize and protect the chromosomes. Telomeres shorten each time a cell divides, and when they reach a certain critical length, they signal the cell to age, or senesce se·nesce intr.v. se·nesced, se·nesc·ing, se·nesc·es To reach later maturity; grow old. [Back-formation from senescent.] Verb 1. . Senescent se·nes·cent adj. Growing old; aging. cells differ from young, normal cells in that they can no longer divide, and the genes they express change, causing the cell to have a destructive effect on the surrounding tissue. A hallmark of HIV disease is increased numbers of activated CD8 cells. At the same time, CD8 cells from HIV-infected patients are abnormal in that they have markedly reduced replicative potential. In this study, the researchers hypothesized that the CD8 cells of patients with chronic HIV might have reached the end of their replicative lifespan due to persistent viral stimulation and increased rounds of CD8 cell division. Confirming their hypothesis, the telomere lengths of CD8 cells in HIV-infected patients were significantly shorter than telomere lengths of CD8 cells in uninfected persons, indicating that extra rounds of cell division had occurred. "This study identifies immune cell senescence as a newly described feature of HIV disease. Replicative senescence has also previously been implicated im·pli·cate tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates 1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot. 2. in atherosclerosis, an age-related cardiovascular disease," stated Dr. West. "These findings have implications for therapeutic intervention in AIDS. They also suggest that telomere length may be used as a marker of disease progression, and for predicting the degree to which a patient's immune system might recover after anti-retroviral therapy. In addition, new therapeutic approaches could result from modulating or delaying the senescence of CD8 cells in patients with HIV." In addition to Dr. West, the authors of the AIDS article included Richard Allsopp, Choy-Pik Chiu, Calvin B. Harley and Bryant Villeponteau of Geron Corporation, and Rita B. Effros, Mary Ann Hausner, Karim Hirji, Lili Wang and Janis V. Giorgi of the UCLA School of Medicine, Los Angeles. Geron is a biopharmaceutical company exclusively focused on discovering and developing therapeutic and diagnostic products based upon common biological mechanisms underlying cancer and other age-related diseases. CONTACT: Geron Corporation Jeryl Hilleman, 415/473-7700 or StratiPoint Group Mike Jackman, 415-326-0420 |
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