Thoughts on Protein Aggregation and Aging

An open access paper: "Aging is the single most important risk factor in human disease in developed countries but when it comes to research on prevention or cures, aging is seldom taken into account. Nevertheless if aging is a significant contributor to age-related conditions, we would hope that an understanding of aging mechanisms could prompt the design of rational therapies. Moreover, if aging causes multiple diseases then it is reasonable to think that pharmacological agents that slow aging could be also effective in preventing or slowing a wide spectrum of diseases. ... Protein aggregation is a hallmark of aging and several age-related pathologies, collectively known as conformational diseases (CD). This similarity strongly suggests a crosstalk between aging and disease. Although it is not clear how protein aggregation occurs, dramatic alterations in the balance of protein synthesis, protein folding and protein degradation (together representing 'protein homeostasis') are likely to play important roles in this process. As a consequence, modified proteins tend to accumulate into soluble oligomers and insoluble aggregates that may actively influence cell function. Neurodegenerative diseases are arguably the best studied CD and the aberrant aggregation of several insoluble molecules [has] long been associated with the development of these pathologies. ... The general picture that that has emerged is that conformationally-altered proteins escape the surveillance of repair and degradation systems, form aggregates, and this process contributes to aging; aging could be therefore a manifestation of a loss in protein homeostasis. This then prompts the question: to what extent could chemical modulation of protein aggregation alter the rate of aging? Furthermore, would such an intervention influence disease pathology? In a recent publication, we addressed this issue by identifying small molecules able to slow protein aggregation in the C. elegans model. We were then able to directly assess the degree to which protein aggregation influences normal aging rates."


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