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Immunity and aging: the enemy within?

DeVeale, Brian and Brummel, Ted and Seroude, Laurent (2004) Immunity and aging: the enemy within? Aging Cell, 3 (4). pp. 195-208. ISSN 1474-9718. doi:10.1111/j.1474-9728.2004.00106.x.

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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.

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Additional Information:© 2004 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland. Accepted for publication 27 May 2004. We thank Rhonda Kristensen for technical assistance, and Luc Poirier and Mike Grotewiel for comments and discussions. Support was received from the Natural Sciences Engineering Research Council of Canada (NSERC), the Institute of Aging of the Canadian Institutes of Health Research (CIHR), the Canada Foundation for Innovation (CFI), the Ontario Innovation Trust (OIT), Human Resources Development Canada (HRDC) and Queen's University Advisory Research Committee (ARC).
Funding AgencyGrant Number
Natural Sciences Engineering Research Council of Canada (NSERC)UNSPECIFIED
Canadian Institutes of Health Research (CIHR)UNSPECIFIED
Canada Foundation for InnovationUNSPECIFIED
Ontario Innovation TrustUNSPECIFIED
Human Resources Development CanadaUNSPECIFIED
Queen's UniversityUNSPECIFIED
Subject Keywords:aging; C. elegans; drosophila; immunity; invertebrates
Issue or Number:4
Record Number:CaltechAUTHORS:20170329-142050647
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Official Citation:DeVeale, B., Brummel, T. and Seroude, L. (2004), Immunity and aging: the enemy within?. Aging Cell, 3: 195–208. doi:10.1111/j.1474-9728.2004.00106.x
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:75518
Deposited By: Tony Diaz
Deposited On:29 Mar 2017 22:06
Last Modified:15 Nov 2021 16:34

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