Ageing associated altered host response to bacterial infection

Abstract

Chapters in which I have elucidated and elaborately described how senescence alters the cellular response to infection, here I demonstrate how senescence in multiple tissues simultaneously contribute to pathogen spread and colonization. The relevance of our in vitro observations of senescent cells being less conducive for bacterial proliferation was extended in vivo using the naturally aged mouse model. In this in vivo model of infection also we find lesser bacterial burden in aged animals and evidence from cell infection data suggests that the accumulation of senescent cells in these organs could perhaps be a major contributing factor. Hence, for the first time we demonstrate an alternate advantage of senescent cell presence and persistence in the system besides its well described contribution to wound healing (Demaria et al, 2014). Ageing associated persistent inflammation and oxidative stress reflect innate immune system preparedness to fight impending infections which is beneficial to an organism witnessing a decline in adaptive immune responses as is associated with the elderly. However, inability to manage these responses beyond its intended control of infection results in excessive damage to the host and subsequent mortality. In summary, this Chapter presents senescence or ageing associated oxidative stress and inflammation as a Goldilocks situation and highlights the need for identification of senotherapeutic agents that can decrease aggravated systemic inflammation without perturbing other host favourable factors like anti-microbial responses for use as adjunct therapy in infected aged individuals.