The heat shock response can induce hormetic benefits: repair and maintenance systems are spurred to greater activity for some time, leading to a healthier, longer-lived organism. Researchers are in search of the pivotal mechanisms of this process, with an eye to targeting them in therapies:
"That which does not kill us, makes us stronger" This famous quote by Friedrich Nietzsche is exemplified by the phenomenon of "hormesis". Exposure of organisms to mild stress fortifies them against subsequent, more severe insults. Yet, the relevant molecular mechanisms remain poorly understood.
[Small heat shock proteins, or sHSPs] constitute a diverse family of proteins with multiple roles. Several ageing theories suggest that longevity positively correlates with the ability of the cell and the organism to resist stress. Ageing influences both general and organelle-specific stress response pathways. Distinct experimental approaches have identified proteins that are abundant in long-lived worms. Intriguingly, the most consistently represented subset is the sHSP group, including the HSP-16 family. We propose that HSP-16.1 mediates its protective effect partly by preserving cellular ionic homeostasis, which is perturbed in the stressful context of ageing.
How could sHSPs protect under unfavorable conditions? In stressed cells, ATP levels drop significantly leading to fatal aggregation of damaged proteins. sHSPs protect proteins from thermal denaturation and irreversible aggregation in an ATP-independent manner. We propose that sHSPs constitute one of the cell's first lines of defense against cell death.