Senescent cells accumulate with age. Transition into a senescent state is, at least initially, a defense against cancer in which cells that are damaged or likely to become damaged due to a dysregulated tissue environment permanently suppress their ability to divide. Many destroy themselves or are destroyed by the immune system, but all too many of them linger on intact. In old skin a large portion of tissue is made up of senescent cells, for example. Cellular senescence as a cancer defense is likely an adaptation of a tool used to shape tissue growth during embryonic development, which might explain why senescent cells secrete a range of molecules that cause harm to surrounding extracellular matrix structures and negatively impact the behavior of nearby cells.
The more senescent cells you have the more their presence degrades the function of tissues and organs. Eventually a large enough number of senescent cells and their secreted signals tip over from being protective against cancer due to removing the ability for damaged cells to replicate to a state of promoting cancer by creating inflammation and other harms in tissue. The best solution to all of this is periodic clearance of senescent cells via some form of targeted cell killing technology, such as those under development in the cancer research community. That approach, like most related to repairing the causes of aging, receives comparatively little attention and funding, however. Here is another of the many examples of the damage done to a particular organ by growing numbers of senescent cells:
Age-associated decline in organ function governs life span. We determined the effect of aging on lung function and cellular/molecular changes of 8- to 32-month old mice. Proteomic analysis of lung matrix indicated significant compositional changes with advanced age consistent with a profibrotic environment that leads to a significant increase in dynamic compliance and airway resistance. The excess of matrix proteins deposition was associated modestly with the activation of myofibroblasts and transforming growth factor-beta signaling pathway. More importantly, detection of senescent cells in the lungs increased with age and these cells contributed toward the excess extracellular matrix deposition observed in our aged mouse model and in elderly human samples.
Mechanistic target of rapamycin (mTOR)/AKT activity was enhanced in aged mouse lungs compared with those from younger mice associated with the increased expression of the histone variant protein, MH2A, a marker for aging and potentially for senescence. Introduction in the mouse diet of rapamycin, significantly blocked the mTOR activity and limited the activation of myofibroblasts but did not result in a reduction in lung collagen deposition unless it was associated with prevention of cellular senescence. Together these data indicate that cellular senescence significantly contributes to the extracellular matrix changes associated with aging in a mTOR 1-dependent mechanism.