Sex-related differences in behavioural markers in adult mice for the prediction of lifespan.

Finding biomarkers to assess the rate of ageing and consequently, to forecast individual lifespan is a challenge in ageing research. We recently published a mathematical model for lifespan prediction in adult female mice using behavioural parameters such as internal locomotion and time spent in open arms in the hole board (HB) and elevated plus maze (EPM) tests, respectively. Nevertheless, it is still not known if these behavioural variables could be useful in forecasting lifespan in male mice. Therefore, two groups of ICR-CD1 mice, male and female were subjected to the EPM, HB and T-maze tests at the adult age. Mice were monitored until they died and individual lifespans were registered. In general, adult male mice showed more anxiety-like behaviours than females. The mathematical model previously developed in females was validated with the female cohort, but found to be suboptimal for lifespan prediction in males. Thus, a new model for male lifespan prediction was constructed including the behavioural variables that were predictive of lifespan in males: time in the central platform of the EPM, inner locomotion, number of groomings and number and duration of head-dippings in the HB. These results confirm that the higher the anxiety-like behaviour at the adult age, the shorter the lifespan.

When will my mouse die? Life span prediction based on immune function, redox and behavioural parameters in female mice at the adult age.

The identification of predictive markers of life span would help to unravel the underlying mechanisms influencing ageing and longevity. For this aim, 30 variables including immune functions, inflammatory-oxidative stress state and behavioural characteristics were investigated in ICR-CD1 female mice at the adult age (N = 38). Mice were monitored individually until they died and individual life spans were registered. Multiple linear regression was carried out to construct an Immunity model (adjusted R2 = 75.8%) comprising Macrophage chemotaxis and phagocytosis and Lymphoproliferation capacity, a Redox model (adjusted R2 = 84.4%) involving Reduced Glutathione and Malondialdehyde concentrations and Glutathione Peroxidase activity and a Behavioural model (adjusted R2 = 79.8%) comprising Internal Locomotion and Time spent in open arms indices. In addition, a Combined model (adjusted R2 = 92.4%) and an Immunity-Redox model (adjusted R2 = 88.7%) were also constructed by combining the above-mentioned selected variables. The models were also cross-validated using two different sets of female mice (N = 30; N = 40). Correlation between predicted and observed life span was 0.849 (P < 0.000) for the Immunity model, 0.691 (P < 0.000) for the Redox, 0.662 (P < 0.000) for the Behavioural and 0.840 (P < 0.000) for the Immunity-Redox model. Thus, these results provide a new perspective on the use of immune function, redox and behavioural markers as prognostic tools in ageing research.

Function, Oxidative, and Inflammatory Stress Parameters in Immune Cells as Predictive Markers of Lifespan throughout Aging.

According to the oxidative-inflammatory theory of aging, there is a link between the function, the oxidative-inflammatory stress state of immune cells, and longevity. However, it is unknown which immune cell parameters can predict lifespan and if there would be any changes in this prediction, depending on the age of the subject. Therefore, a longitudinal study in mice was performed analysing immune function (chemotaxis of macrophages and lymphocytes, phagocytosis of macrophages, natural killer (NK) activity, and lymphoproliferation capacity), antioxidant (catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities as well as reduced glutathione (GSH) concentrations), oxidant (oxidized glutathione (GSSG), superoxide anion, and malondialdehyde (MDA) concentrations), and inflammation-related markers (basal release of IL-1ß, IL-6, TNF-α, and IL-10) in peritoneal leukocytes from mice at the adult, mature, old, very old, and long-lived ages (40, 56, 72, 96, and 120 ± 4 weeks of age, respectively). 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, GPx activity, and GSH, MDA, 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 (NK activity, CAT and GR activities, and IL-6 and IL-1ß concentrations), and as such, they could reflect some of the adaptive mechanisms underlying the achievement of high longevity. Nevertheless, although preliminary, the results of the present study provide a new perspective on the use of function, redox, and inflammatory parameters in immune cells as prognostic tools in aging research and represent a novel benchmark for future work aimed at prediction of lifespan.