Protein misfolding is a form of damage that accumulates with age. Here researchers show that some misfolds are more important than others: "Misfolded and damaged proteins spell trouble and are common to all human neurodegenerative diseases and many other age-associated diseases. But when during a lifespan do proteins start to misbehave? A new [study] reports that protein damage can be detected much earlier than we had thought, long before individuals exhibit symptoms. But the study also suggests if we intervene early enough, the damage could be delayed. In studying seven different proteins of the worm C. elegans, the researchers discovered that each protein misfolds at the same point: during early adulthood and long before the animal shows any behavioral, or physiological, change. ... The misfolding coincided with the loss of a critical protective cellular mechanism: the ability to activate the heat shock response, an ancient genetic switch that senses damaged proteins and protects cells by preventing protein misfolding." You might recall that enhanced heat shock response is how SIRT1 is thought to influence health and longevity, and there is a growing interest in manipulating the heat shock response as the basis for longevity and cancer therapies.