Pharmacological inhibition of USP14 delays proteostasis-associated aging in a proteasome-dependent but foxo-independent manner.
Abstract
Aging is often accompanied by a decline in proteostasis, manifested as an increased propensity for misfolded protein aggregates, which are prevented by protein quality control systems, such as the ubiquitin-proteasome system (UPS) and macroautophagy/autophagy. Although the role of the UPS and autophagy in slowing age-induced proteostasis decline has been elucidated, limited information is available on how these pathways can be activated in a collaborative manner to delay proteostasis-associated aging. Here, we show that activation of the UPS via the pharmacological inhibition of USP14 (ubiquitin specific peptidase 14) using IU1 improves proteostasis and autophagy decline caused by aging or proteostatic stress in
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Research summary
The paper addresses the decline in proteostasis associated with aging and explores a pharmacological approach to enhance the ubiquitin-proteasome system, which is relevant to the mechanisms of aging. While it presents solid research on a specific intervention, the findings appear to be an incremental advance rather than a groundbreaking discovery that could significantly alter the understanding or treatment of aging processes.
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