How to outlive the evolutionary biological clock? A neuro-endocrine-immune perspective

Aging is generally characterized as a gradual increase in tissue damage, associated with cell senescence, low-grade systemic inflammation and increased incidence of age-related diseases. The extent to which tissue damage results from a gradual decline in immune regulation, which consequently compromises the body capacity to repair damages, has not been fully explored. In this lecture, I will describe the lifespan accumulation of specific dysregulated lymphocyte subsets, their functional properties and their coevolution with systemic inflammation in the process of declined immunity and tissue repair capacity with age. These will be discussed in the context of pubertal-induced thymus involution, dysregulation of the hypothalamus-pituitary-adrenal (HPA) and the hypothalamus-pituitary-gonadal (HPG) axes, as processes that culminate at driving age-related diseases and neurodegeneration. Early related biomarkers and therapeutic strategies will be discussed.