TY - JOUR
T1 - Identification of high caspase-3 mRNA expression as a unique signature profile for extremely old individuals
AU - Lacelle, Chantale
AU - Xu, Suying
AU - Wang, Eugenia
N1 - Funding Information:
The authors thank Mr. Alan N. Bloch for proofreading this manuscript, Mr. Louis-Bruno Ruest for helpful discussions, and Mr. Jen-Mou Chen, Ms. Marian Wang and Dr Yih-Jing Tang for their technical assistance. We also thank the Department of Microbiology and Immunology of McGill University (Montreal, Canada) and the James Graham Brown Cancer Center of the University of Louisville (Louisville, Kentucky) for the use of their FACS Core Facilities. This work was supported by National Institutes of Health Grant R37AG0T444 from the National Institute on Aging to E.W., and by the Defense Advanced Research Project Agency (DARPA) of the Department of Defense of the United States of America (also to E.W.).
PY - 2002/4/30
Y1 - 2002/4/30
N2 - Apoptosis, or programmed cell death, is important for maintaining tissue homeostasis, as it permits the elimination of damaged, functionless or unwanted cells. As we age, our immune system undergoes constant remodeling, during which age-associated changes in immune parameters, including decreased naïve and increased memory T cells, have been reported. However, excessive immune cell loss, rendering the elderly more vulnerable to infections, and inappropriate deletion of damaged or functionless lymphocytes, can contribute to the development of age-associated diseases. As such, we studied the mRNA expression of cell death (specifically caspase) genes in nonagenarians and centenarians, successful models of ageing who have survived or avoided age-associated diseases, as well as in their younger counterparts and found that population composed of extremely old individuals shows a unique pattern of caspase mRNA expression, characterized by high levels of caspase-1 and -3, and low levels of caspase-8, mRNA while those composed of old individuals are characterize by high level of caspase-8 mRNA expression. Furthermore, we show that the described changes in caspases mRNA do not appear to results from age-related changes in PBMC composition, such as decreases in CD24. Therefore, we suggest that unique patterns of caspase mRNA results from the regulation of message abundance on a per cell basis, via a putative regulation of caspase genes at the transcription or RNA processing level, rather than changes in immune profiles.
AB - Apoptosis, or programmed cell death, is important for maintaining tissue homeostasis, as it permits the elimination of damaged, functionless or unwanted cells. As we age, our immune system undergoes constant remodeling, during which age-associated changes in immune parameters, including decreased naïve and increased memory T cells, have been reported. However, excessive immune cell loss, rendering the elderly more vulnerable to infections, and inappropriate deletion of damaged or functionless lymphocytes, can contribute to the development of age-associated diseases. As such, we studied the mRNA expression of cell death (specifically caspase) genes in nonagenarians and centenarians, successful models of ageing who have survived or avoided age-associated diseases, as well as in their younger counterparts and found that population composed of extremely old individuals shows a unique pattern of caspase mRNA expression, characterized by high levels of caspase-1 and -3, and low levels of caspase-8, mRNA while those composed of old individuals are characterize by high level of caspase-8 mRNA expression. Furthermore, we show that the described changes in caspases mRNA do not appear to results from age-related changes in PBMC composition, such as decreases in CD24. Therefore, we suggest that unique patterns of caspase mRNA results from the regulation of message abundance on a per cell basis, via a putative regulation of caspase genes at the transcription or RNA processing level, rather than changes in immune profiles.
KW - Ageing
KW - Apoptosis
KW - Caspases
KW - Longevity
KW - MRNA
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U2 - 10.1016/S0047-6374(02)00005-2
DO - 10.1016/S0047-6374(02)00005-2
M3 - Article
C2 - 12044963
AN - SCOPUS:0037198033
SN - 0047-6374
VL - 123
SP - 1133
EP - 1144
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
IS - 8
ER -