Elsevier

Seminars in Nephrology

Volume 29, Issue 6, November 2009, Pages 555-568
Seminars in Nephrology

Chronic Inflammation Potentiates Kidney Aging

https://doi.org/10.1016/j.semnephrol.2009.07.002Get rights and content

Summary

Chronic inflammation, characterized by increased serum levels of tumor necrosis factor-α, interleukin-6, C-reactive protein, and plasminogen activator inhibitor-1, and the presence of inflammatory-related diseases, are seen commonly in aging. Both the dysregulation of immune cells and phenotypic changes in parenchymal cells may contribute to chronic inflammation in aging. Moreover, senescent cells are an important source of inflammatory factors. Oxidative stress, via activation of p38 and c-Jun N-terminal kinase and induction of cell senescence, is likely to play a critical role in inflammation. Endoplasmic reticulum stress also may be present in aging and be involved in inflammation. Advanced glycation end products also are important contributors to inflammation in aging. Because the kidney is a major site for the excretion, and perhaps the degradation, of advanced glycation end products and small inflammatory molecules, reduced renal function in aging may promote oxidative stress and inflammation. Chronic inflammation in turn may potentiate the initiation and progression of lesions in the aging kidney.

Section snippets

The Association of Chronic Inflammation with Aging and Aging Renal Function Decline

Accumulating evidence suggests that aging often represents a state of chronic low-grade inflammation characterized by increased serum levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-1–receptor antagonist, fibrinogen, and C-reactive protein (CRP).6, 7, 8 For instance, the levels of fibrinogen and CRP were higher in healthy elders older than 60 years than in adults younger than 45 years.7 Chronic inflammation may play an important role in aging-related diseases such as

The Cellular Sources of Chronic Inflammation in Aging

The cellular basis of chronic inflammation in aging is unknown. A dysregulation of the immune system in aging is believed to play an important role in chronic inflammation.14 Generally, the functions of immune cells are decreased in older people. Fewer B and T cells are produced in older human beings.14, 15 In addition, B cells from older individuals generated antibodies with lower affinity to antigen and had an impaired ability to undergo class-switch recombination compared with B cells from

The Underlying Mechanisms of Chronic Inflammation in Aging

Oxidative stress is implicated as a critical factor for aging and aging-related chronic inflammation. The levels of reactive oxygen and nitrogen species are increased in aging in all the organs, including the kidney, owing to excessive production of free radicals and decreased anti-oxidant defenses. Free radicals or nonradical oxidants constantly are generated by aerobic metabolism and may be an element of some signaling events such as transducing proliferative signals from platelet-derived

A Role of Chronic Inflammation in Kidney Aging

Although 24% of individuals age 65 years and older have decreased renal function, very few develop end-stage renal disease unless there is a second injury, suggesting that kidney aging is either a slowly progressing process or that the current method of measuring renal function overestimates the degree of renal functional loss in aging. This slow progression is mirrored in aging C57B6 mice, a model of kidney aging.24 Because aging could be defined more clearly in females by cessation of ovarian

Conclusions and Future Directions

The advances made in recent years in ROS signaling, T-cell immunobiology, and cell senescence have clarified some of the molecular mechanisms and cellular aspects of chronic inflammation in aging. In addition, extensive studies on the mechanisms of calorie restriction in prolonging life span and preventing organ aging have led to the identification of nicotinamide adenine dinucleotide (NAD(+))-dependent histone deacetylases sirtuins as an important subgroup of molecules that actively are

Acknowledgment

The authors thank Dr. Gary Striker for critical reading of and comments on the manuscript.

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    Supported by National Institutes of Health grant 5R01AG027628-03 (F.Z.).

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