Apoptosis, repair and senescence

Roger Highmore
2019 Figshare  
We examine how an organism might use apoptosis, repair or senescence to deal with the threat posed by an errant cell. We consider risks and costs to the organism for each type of response and discuss how these evolve as the organism ages. We suggest how clusters of senescent cells may affect older organisms.Instead of using a one-size-fits-all strategy to optimise the relationship between risk and cost, an organism might orchestrate an ensemble of strategies, each best suited to a particular
more » ... to a particular situation. TP53 coding multiple isoforms may be part of such an approach, allowing responses to errant cells to vary with factors such as tissue type, kind of damage and time (age). In this view messages bearing environmental status information cause TP53 to express isoforms of p53 that best manage risk at particular locations and times.If an organism's response to damage is based on a compromise between risk and cost, an enhanced short-term response to damage can be induced by some combination of raising the assessed risk (e.g., by manipulating messages bearing information about the damage) and reducing the perceived cost (e.g., by manipulating messages carrying information about available resources).One way to counter the dangers posed by errant cells is to facilitate production of new, substitute cells that can replace imperfect cells destroyed by apoptosis. Fresh sources of substitute cells will encourage TP53 to express isoforms of p53 that mediate apoptosis.Organs within one body may coordinate and synchronise their risk horizons by exchanging messages through the bloodstream.Medical interventions might intercept and manipulate these blood-borne messages in attempts to eliminate particular threats, or to preserve resources for use later in life.We suggest a model where diseased cells can be suppressed by suitable interplay between the kinetics of disease formation, apoptosis and replacement cell creation.
doi:10.6084/m9.figshare.5394400.v12 fatcat:iruakfi2xffsvlp6chpqdkqqhy