Heat Shock Proteins and Hormesis as a Basis for Therapy
As this open access paper demonstrates, researchers continue to discuss manipulation of heat shock proteins and the hormetic response to mild levels of cell damage or stress as a basis for possible therapies to slow some of the consequences of aging. These proteins are a crucial part of cellular housekeeping mechanisms, and increasing their activity has been fairly conclusively demonstrated to be beneficial in a variety of species. Despite more than a decade of intent to do something along these lines, and some recent signs of progress, there has been little to no concrete movement beyond the laboratory, however.
Modulation of endogenous cellular defense mechanisms via the stress response signaling represents an innovative approach to therapeutic intervention in diseases causing tissue damage, such as neurodegeneration, for example is reported how drugs that modulate proteostasis by inhibiting Hsp90 function or promoting Hsp70 function enhance the degradation of the critical aggregating proteins and ameliorate toxic symptoms in cell and animal disease models. Efficient functioning of maintenance and repair processes seems to be crucial for both survival and physical quality of life. This is accomplished by a complex network of the so-called longevity assurance processes, which are composed of several genes termed vitagenes. Consistently, by maintaining or recovering the activity of vitagenes can be possible to delay the aging process and decrease the occurrence of age-related diseases with resulting prolongation of a healthy life span.There is now strong evidence to suggest that factors such as oxidative stress and disturbed protein metabolism and their interaction in a vicious cycle are central to Alzheimer's disease pathogenesis. Brain-accessible antioxidants, potentially, may provide the means of implementing this therapeutic strategy of delaying the onset of Alzheimer's disease, and more in general all degenerative diseases associated with oxidative stress. As one potentially successful approach, potentiation of endogenous secondary antioxidants systems can be achieved by interventions which target the heme oygenase/carbon monoxide and/or Hsp70 systems.
Reports exist of enhanced longevity via treatment with a large number of agents in a wide range of animal models displaying hormetic dose responses. The generality of the hormetic dose response, being independent of biological model, endpoint, inducing agent and mechanism and with its quantitative features being a measure of plasticity constrained biological performance, strongly suggests that attempts to extend normal lifespan via alteration of metabolism will be likewise limited to the 30-60% as has been typically reported. Thus, hormesis has a fundamental role in aging research, affecting both the quality and the length of life as well as affecting the research methods (e.g., study design, statistical power, etc.) by which such biological concepts are studied.