Immunity and aging: the enemy within?

被引:139
作者
DeVeale, B
Brummel, T
Seroude, L [1 ]
机构
[1] Queens Univ, Dept Biol, BioSci Complex, Kingston, ON K7L 3N6, Canada
[2] CALTECH, Div Biol, Pasadena, CA 91125 USA
[3] Sam Houston State Univ, Dept Biol Sci, Huntsville, TX 77341 USA
关键词
aging; C; elegans; drosophila; immunity; invertebrates;
D O I
10.1111/j.1474-9728.2004.00106.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Functional analyses of changes in the immune response indicate that aging is associated with a decline of adaptive immunity whereas innate immunity is ramped up. Gene expression studies also support age-dependent changes in immunity. Studies using a large panel of methodologies and multiple species show that some of the most dramatic transcriptional changes that occur during aging are associated with immunity. This observation leads to two fundamental questions: (1) Why is the immune response altered with age? (2) Is this a consequence of aging or does it contribute to it? The origin of these changes and the mechanistic relationship among them as well as with aging must be identified. In mammals, this task is complicated by the interdependence of the innate and adaptive immune systems. The value of invertebrates as model organisms to help answer these questions is presented. This includes a description of the immune response in invertebrate models and how it compares with vertebrates, focusing on conserved pathways. Finally, these questions are explored in light of recent reports and data from our laboratory. Experimental alterations of longevity indicate that the differential expression of immunity-related genes during aging is linked to the rate of aging. Long-lived nematodes are more resistant to pathogens and blocking the expression of immune-related genes can prevent lifespan extension. These observations suggest that the immune response has a positive effect on longevity, possibly by increasing fitness. By contrast, it has been reported that activation of the immune system can reduce longevity upon starvation. We also observed that deregulation of the immune response has drastic effects on viability and longevity in Drosophila. These data suggest that the immune response results in a trade-off between beneficial and detrimental effects that might profoundly affect the aging process. Given this, immunity may be an ally early in life, but turns out to be an enemy as we age.
引用
收藏
页码:195 / 208
页数:14
相关论文
共 140 条
[1]   Programmed cell death mediated by ced-3 and ced-4 protects Caenorhabditis elegans from Salmonella typhimurium-mediated killing [J].
Aballay, A ;
Ausubel, FM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (05) :2735-2739
[2]   Caenorhabditis elegans innate immune response triggered by Salmonella enterica requires intact LPS and is mediated by a MAPK signaling pathway [J].
Aballay, A ;
Drenkard, E ;
Hilbun, LR ;
Ausubel, FM .
CURRENT BIOLOGY, 2003, 13 (01) :47-52
[3]   T cell activation and the cytoskeleton [J].
Acuto, O ;
Cantrell, D .
ANNUAL REVIEW OF IMMUNOLOGY, 2000, 18 :165-+
[4]   Signaling role of hemocytes in Drosophila JAK/STAT-dependent response to septic injury [J].
Agaisse, H ;
Petersen, UM ;
Boutros, M ;
Mathey-Prevot, B ;
Perrimon, N .
DEVELOPMENTAL CELL, 2003, 5 (03) :441-450
[5]   Dorsal closure in drosophila.: A genetic model for wound healing? [J].
Agnès, F ;
Noselli, S .
COMPTES RENDUS DE L ACADEMIE DES SCIENCES SERIE III-SCIENCES DE LA VIE-LIFE SCIENCES, 1999, 322 (01) :5-13
[6]   Toll-like receptors: critical proteins linking innate and acquired immunity [J].
Akira, S ;
Takeda, K ;
Kaisho, T .
NATURE IMMUNOLOGY, 2001, 2 (08) :675-680
[7]   Differential signaling by lymphocyte antigen receptors [J].
AlberolaIla, J ;
Takaki, S ;
Kerner, JD ;
Perlmutter, RM .
ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 :125-154
[8]   Characterization of mediators of microbial virulence and innate immunity using the Caenorhabditis elegans host-pathogen model [J].
Alegado, RA ;
Campbell, MC ;
Chen, WC ;
Slutz, SS ;
Tan, MW .
CELLULAR MICROBIOLOGY, 2003, 5 (07) :435-444
[9]   Production of Nε-(carboxymethyl)lysine is impaired in mice deficient in NADPH oxidase -: A role for phagocyte-derived oxidants in the formation of advanced glycation end products during inflammation [J].
Anderson, MM ;
Heinecke, JW .
DIABETES, 2003, 52 (08) :2137-2143
[10]  
Aydar Y, 2002, EUR J IMMUNOL, V32, P2817, DOI 10.1002/1521-4141(2002010)32:10<2817::AID-IMMU2817>3.0.CO