Oxidative and Inflammatory Markers in Immune Cells as Predictors of Lifespan
Researchers here analyze markers in mice that are reflective of the decline of the immune system into the state of inflammaging, in which chronic inflammation disrupts normal cell and tissue function throughout the body. Unsurprisingly, some of these markers are predictive of life span. A faster decline of the immune system, for whatever underlying reason, will tend to lead to a shorter life expectancy. The immune system is vital in defense against pathogens, destruction of cancerous cells, and clearance of senescent cells. When these functions decline, the result is increased risk of age-related disease and mortality.
Several theories have been proposed to explain the aging process. The oxidative-inflammatory theory of aging links the age-related increase in oxidative stress with the chronic low-grade inflammation, the so-called "inflammaging", through the interplay of the immune system. It is known that the age-related increase in oxidative stress impairs the correct functioning of cells. Given that oxidation and inflammation are interlinked processes, the increase in oxidative stress in immune cells results in an increased release of proinflammatory mediators, giving as a result the age-related establishment of a chronic oxidative and inflammatory stress.
According to this theory, a relationship has been found between the oxidative and inflammatory states of immune cells, their functional capacity, and the lifespan of a subject. In this regard, it has been demonstrated that centenarians have immune cell function and redox parameters similar to those in adults, despite their advanced age. However, if they maintain this optimal functionality during their whole lifespan or they undergo some remodelling of these parameters during aging is unknown. Therefore, a deep understanding of these subjects would require their follow-up throughout the aging process to shed light into which changes or adaptations are the "successful ones." Since a longitudinal study is impossible to carry out in human subjects throughout the whole aging process, mice, which have a mean longevity of two years, were used for this work.
Thus, a longitudinal study was performed analysing several functions (macrophage chemotaxis and phagocytosis, natural killer activity, lymphocyte chemotaxis, and lymphoproliferation capacity), redox parameters (catalase, glutathione peroxidase, and glutathione reductase activities, reduced and oxidized glutathione, and superoxide anion and malondialdehyde concentrations), and inflammatory mediators (basal release of IL-6, IL-1β, TNF-α, and IL-10) in peritoneal leukocytes throughout the aging process of mice. This approach allowed us to address three important questions: (i) which markers are the most important predictors of remaining longevity in adult or middle life? (ii) Are the same parameters predictive of successful aging at very advanced age? (iii) Which changes or adaptations an individual experiences throughout his/her lifetime that allow the attainment of extreme longevity?
The results reveal that some of the investigated parameters are determinants of longevity at the adult age (lymphoproliferative capacity, lymphocyte chemotaxis, macrophage chemotaxis and phagocytosis, glutathione peroxidase activity, and glutathione, malondialdehyde, IL-6, TNF-α, and IL-10 concentrations), and therefore, they could be proposed as markers of the rate of aging. However, other parameters are predictive of extreme longevity only at the very old age (natural killer activity, catalase, and glutathione reductase activities, and IL-6 and IL-1β concentrations), and as such, they could reflect some of the adaptive mechanisms underlying the achievement of high longevity.