Proteostasis and Aging

The maintenance of functional proteins in a cell relies upon, at the simplest level, balancing protein synthesis with protein degradation to sustain steady-state protein levels. The ways that the cell accomplishes this are complex and includes the regulation of protein synthesis, folding, trafficking, maintenance, and degradation. This highly evolved process, known as protein homeostasis or proteostasis is a fundamental process that has evolved to maintain a healthy and functional set of proteins (a proteome). Since proteins carry out the majority of the work in the cell, regulating proteostasis is a critical task to maintain a healthy cell. In turn, deterioration of the proteostasis network has broad effects on cellular function. Aging represents a challenge to maintaining proteostasis. Declining function of protein quality control mechanisms combined with increasing damage to proteins result in significant stress and challenge the proteostasis network. While the proteostasis network has evolved to respond to stress on the proteome, a combination of challenges that occur during the aging process often overwhelms these safe-guards and can result in cellular dysfunction and death. This collapse in proteostasis is no more apparent than in late-onset neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, Amyotrophic Lateral Sclerosis, and the prion diseases. Each of these disorders is characterized by the unnatural production of aberrant proteins that challenge and ultimately overwhelm the proteostasis network resulting in severe cellular dysfunction. A hallmark of disrupted...

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