SIPS as a model to study age-related changes in proteolysis and aggregate formation.

Aging is accompanied by the accumulation of cellular damage over time in response to stress, lifestyle and environmental factors ultimately leading to age-related diseases and death. Additionally, the number of senescent cells increases with age. Senescence is most likely not a static endpoint, it represents a series of hallmarks including morphological changes, alterations in protein turnover and accumulation of protein aggregates. The importance of protein oxidation and aggregate accumulation in the progression of aging is not yet fully understood and research to what extent the accumulation of oxidized proteins has an effect on senescence and the aging process is still ongoing. To study the mechanisms of aging, the impact of senescence and the role of protein aggregates on the aging process, cell culture models are useful tools. Most notably stress induced premature senescence (SIPS) models have contributed to the identification of mechanisms involved in the aging process and helped unravel the age-related changes in proteolysis and the importance of protein aggregation. Here we review characteristics of replicative and premature senescence, how to induce most frequently used senescence models and gained knowledge on age-related changes in the major proteolytic systems.