Both quality control and pace of production of proteins in cells are linked to aging. When comparing species and lineages with different life spans, long-lived mutants of short-lived species such as nematode worms exhibit a slower rate of protein synthesis. The same is true in yeast. Equally, the long-lived naked mole-rat exhibits highly efficient quality control in protein synthesis when compared to short-lived rodent species of a similar size. It is also the case that for any given individual, the quality control of protein synthesis becomes worse with age, and this - like stochastic mutation of DNA, and for similar reasons - is thought to be a contributing factor in the progression of degenerative aging. That said, where exactly it sits in the long chains of cause and effect between first cause of aging and final downstream outcome of aging is up for debate.
Aging is characterized by the accumulation of various forms of damage as well as by other age-related deleterious changes. These changes generally have negative, deleterious consequences for organisms as they age. Different living systems differ in their metabolic strategies, resulting in different types and levels of damage production, therefore have evolved both unique and common mechanisms to counteract some of these deleterious changes. These mechanisms also limit the transfer of damage to progeny. The damage-producing and protective mechanisms are mostly genetically controlled, differ among taxonomic groups and are important in defining the lifespan of organisms. Nevertheless, the general principles of cell and organismal organization make damage accumulation inevitable for most multicellular organisms.
In this review, we discuss age-related changes in one of the most important and abundant components of any cell, and therefore of the whole organism - the proteome. Functionality of the whole system of proteins in any organism requires maintenance of a precise balance of synthesis, degradation and function of each and every protein, while aging often shifts this balance, resulting in pathology. Being the end-point of the implementation of genetic information, the proteome accumulates damage generated during this process. The effectiveness of proteostasis control systems, which maintain and recycle the proteome, is diminished with age, leading to the accumulation of damaged proteins and molecules, which in turn inhibit cell functionality and thus cause age-related dysfunction.
Every step in protein lifecycle, most notably protein synthesis and degradation, is relevant to the aging process and, indeed, has been shown to change with age and likely define lifespan. While changes in protein degradation systems during aging are relatively well studied, alterations in protein synthesis still remain to be elucidated. Does the overall level of protein synthesis change with age? Which components of the translation apparatus are affected by aging? Do errors in protein synthesis increase in older organisms? Is there age-dependent regulation of protein synthesis at the level of translation? Answering these questions is necessary for understanding the mechanisms of aging and lifespan control.