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Review
. 2014 Jun;36(3):9626.
doi: 10.1007/s11357-014-9626-3. Epub 2014 Feb 21.

P62/SQSTM1 at the interface of aging, autophagy, and disease

Alessandro Bitto  1 , Chad A Lerner, Timothy Nacarelli, Elizabeth Crowe, Claudio Torres, Christian Sell
Affiliations
Review

P62/SQSTM1 at the interface of aging, autophagy, and disease

Alessandro Bitto et al. Age (Dordr). 2014 Jun.

Abstract

Advanced age is characterized by increased incidence of many chronic, noninfectious diseases that impair the quality of living of the elderly and pose a major burden on the healthcare systems of developed countries. These diseases are characterized by impaired or altered function at the tissue and cellular level, which is a hallmark of the aging process. Age-related impairments are likely due to loss of homeostasis at the cellular level, which leads to the accumulation of dysfunctional organelles and damaged macromolecules, such as proteins, lipids, and nucleic acids. Intriguingly, aging and age-related diseases can be delayed by modulating nutrient signaling pathways converging on the target of rapamycin (TOR) kinase, either by genetic or dietary intervention. TOR signaling influences aging through several potential mechanisms, such as autophagy, a degradation pathway that clears the dysfunctional organelles and damaged macromolecules that accumulate with aging. Autophagy substrates are targeted for degradation by associating with p62/SQSTM1, a multidomain protein that interacts with the autophagy machinery. p62/SQSTM1 is involved in several cellular processes, and its loss has been linked to accelerated aging and to age-related pathologies. In this review, we describe p62/SQSTM1, its role in autophagy and in signaling pathways, and its emerging role in aging and age-associated pathologies. Finally, we propose p62/SQSTM1 as a novel target for aging studies and age-extending interventions.

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Figures

Fig. 1
Fig. 1
Architecture, interaction domain, and functions of the p62/SQSTM1 protein. The interacting partners of each domain are listed in black, while the functions each domain mediates are depicted in red
See this image and copyright information in PMC

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