[Molecular mechanisms of age-related lymphocyte dysfunction].
Aging is classically accompanied by a dysregulation of the immunologic machinery. As a consequence, the immune response developed in senescent organisms is usually inappropriate, often inefficient, sometimes aberrant, and potentially detrimental. The age-associated immune dysfunction may be implicated to some degree in the extreme susceptibility of the elderly to infection and neoplasia and may even participate in various aspects of senescence. The current understanding of the molecular mechanisms underlying immunosenescence is still fragmentary. The most extensively studied phenomenon is the progressive decline in the proliferative capacities of T lymphocytes with aging. The loss of proliferative potential in response to antigenic challenge is a characteristic feature of immune senescence. It is directly implicated in the emergence of the age-related immune deficiency. The purpose of this review is to show how the accumulation of various biochemical lesions with advancing age leads to the failure of a critical cell function, namely the activation-induced lymphocyte proliferation. The biochemical modifications responsible for the defect in transduction and execution of the proliferative signal are analyzed as a function of age. The multiple alterations observed on the various biochemical pathways may appear as a consequence of a unique deleterious mechanism more fundamentally related to the process of senescence such as the inability to cope with oxidative stress.
Proust
J J
JJ
Département de Gériatrie, Hôpitaux Universitaires de Genève, Université de Genève, Suisse.
Quadri
R A
RA
Arbogast
A
A
Phelouzat
M A
MA
D000367:Age Factors; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D015870:Gene Expression; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D006133:Growth Substances; D014157:Transcription Factors; D018844:Cyclin-Dependent Kinases
Mécanismes moléculaires du dysfonctionnement lymphocytaire lié à l'âge.