The consequences of environmental conditions for antagonistic pleiotropic effects of cellular senescence

Senescence is a cellular stress response activated by irreparable DNA damage. Senescent cells accumulate in virtual all tissues during ageing and promote the onset of age-related diseases such as cancer, arteriosclerosis and Alzheimer. This happens for example via the secretion of various inflammatory factors which can directly affect the growth and metastatic capacity of cancer cells. However, senescent cells have also beneficial effects such as promoting optimal cutaneous wound healing. It is well know that environmental conditions such as caloric intake and oxygen availability can influence ageing and wound healing. For example, caloric restriction leads to a reduction in wound healing speed and increase lifespan. If these environmental conditions influence biological processes such as ageing and wound healing via effects on senescent cells remains largely unknown. In this thesis it is described that caloric restriction is associated to a reduction in senescent cells in human and mouse tissues during aging. During wound healing the number of senescent cells is reduced and wound healing speed is limited by caloric restriction. In Chapter 5, it is described that senescent cells secrete less inflammatory factors when kept under low oxygen culture conditions. In addition, lower oxygenated tissues and tissue regions show lower levels of inflammatory factors but the number of senescent cells are approximately equal. By mimicking low oxygen conditions using drugs that are often taken as doping drugs, we might be able to limit negative effects of senescent cells