Ruano, Diego2022-10-072022-10-072021-06-17Ruano D. Proteostasis Dysfunction in Aged Mammalian Cells. The Stressful Role of Inflammation. Front Mol Biosci. 2021 Jun 17;8:658742.http://hdl.handle.net/10668/4244Aging is a biological and multifactorial process characterized by a progressive and irreversible deterioration of the physiological functions leading to a progressive increase in morbidity. In the next decades, the world population is expected to reach ten billion, and globally, elderly people over 80 are projected to triple in 2050. Consequently, it is also expected an increase in the incidence of age-related pathologies such as cancer, diabetes, or neurodegenerative disorders. Disturbance of cellular protein homeostasis (proteostasis) is a hallmark of normal aging that increases cell vulnerability and might be involved in the etiology of several age-related diseases. This review will focus on the molecular alterations occurring during normal aging in the most relevant protein quality control systems such as molecular chaperones, the UPS, and the ALS. Also, alterations in their functional cooperation will be analyzed. Finally, the role of inflammation, as a synergistic negative factor of the protein quality control systems during normal aging, will also be addressed. A better comprehension of the age-dependent modifications affecting the cellular proteostasis, as well as the knowledge of the mechanisms underlying these alterations, might be very helpful to identify relevant risk factors that could be responsible for or contribute to cell deterioration, a fundamental question still pending in biomedicine.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/AgingProteasomeAutophagyInflammationProteostasisCell stress and agingAmyotrophic lateral sclerosisMolecular chaperonesEnvejecimientoInhibidores de proteasomaAutofagiaInflamaciónSenescencia celularEsclerosis amiotrófica lateralChaperonas molecularesMedical Subject Headings::Persons::Persons::Age Groups::Adult::AgedMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Proteostasis DeficienciesMedical Subject Headings::Diseases::Nervous System Diseases::Neurodegenerative Diseases::Motor Neuron Disease::Amyotrophic Lateral SclerosisMedical Subject Headings::Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Cognition::ComprehensionMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::IncidenceMedical Subject Headings::Diseases::NeoplasmsMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::AgingMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Molecular ChaperonesMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::InflammationMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk FactorsMedical Subject Headings::Diseases::Endocrine System Diseases::Diabetes Mellitusreview article34222330open access10.3389/fmolb.2021.6587422296-889XPMC8245766