Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes?

Tamas Fulop, Anis Larbi, Gilles Dupuis, Aurélie Le Page, Eric H Frost, Alan A Cohen, Jacek M Witkowski, Claudio Franceschi, Tamas Fulop, Anis Larbi, Gilles Dupuis, Aurélie Le Page, Eric H Frost, Alan A Cohen, Jacek M Witkowski, Claudio Franceschi

Abstract

The immune system is the most important protective physiological system of the organism. It has many connections with other systems and is, in fact, often considered as part of the larger neuro-endocrine-immune axis. Most experimental data on immune changes with aging show a decline in many immune parameters when compared to young healthy subjects. The bulk of these changes is termed immunosenescence. Immunosenescence has been considered for some time as detrimental because it often leads to subclinical accumulation of pro-inflammatory factors and inflamm-aging. Together, immunosenescence and inflamm-aging are suggested to stand at the origin of most of the diseases of the elderly, such as infections, cancer, autoimmune disorders, and chronic inflammatory diseases. However, an increasing number of immune-gerontologists have challenged this negative interpretation of immunosenescence with respect to its significance in aging-related alterations of the immune system. If one considers these changes from an evolutionary perspective, they can be viewed preferably as adaptive or remodeling rather than solely detrimental. Whereas it is conceivable that global immune changes may lead to various diseases, it is also obvious that these changes may be needed for extended survival/longevity. Recent cumulative data suggest that, without the existence of the immunosenescence/inflamm-aging duo (representing two sides of the same phenomenon), human longevity would be greatly shortened. This review summarizes recent data on the dynamic reassessment of immune changes with aging. Accordingly, attempts to intervene on the aging immune system by targeting its rejuvenation, it may be more suitable to aim to maintain general homeostasis and function by appropriately improving immune-inflammatory-functions.

Keywords: healthspan; immune-adaptation; immunometabolism; immunoremodeling; immunosenescence; inflamm-aging; longevity.

Figures

Figure 1
Figure 1
The new paradigm for the role of inflamm-aging and immunoadaptation/remodeling in the aging process. *Optimization: all three processes increase in concert, balancing each other. **Deterioration: inflamm-aging increases, and is not balanced by opposite processes of anti-inflamm-aging and immune-adaptation/remodeling, which are decreasing. We mean by anti-inflamm-aging all compensatory mechanisms which emerged to compensate the chronic inflamm-aging. The most important diseases that could have an inflamm-aging component are cancers, cardiovascular diseases, and neurodegenerative diseases.

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