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Author

Laura C.D. Pomatto

Other affiliations: Baylor College of Medicine
Bio: Laura C.D. Pomatto is an academic researcher from University of Southern California. The author has contributed to research in topics: Proteasome & Oxidative stress. The author has an hindex of 16, co-authored 19 publications receiving 985 citations. Previous affiliations of Laura C.D. Pomatto include Baylor College of Medicine.

Papers
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Journal ArticleDOI
TL;DR: Drosophila melanogaster is developed as a model for sex-specific stress adaptation regulated by the Lon protease, with potential implications for understanding sexual dimorphism in human disease.

198 citations

Journal ArticleDOI
TL;DR: Increasing evidence is summarized that the 20S core proteasome constitutes the major conformation of the proteasomesome system and that it is far from a latent protease requiring activation by binding regulators.

165 citations

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TL;DR: It is proposed that the regulation of Lon is biphasic, in that it is up-regulated during transient stress and down- regulated during chronic stress and aging, and it is suggested that the loss of Lon responsiveness may be a significant factor in Aging, and in age-related diseases.
Abstract: The elimination of oxidatively modified proteins is a crucial process in maintaining cellular homeostasis, especially during stress. Mitochondria are protein-dense, high traffic compartments, whose polypeptides are constantly exposed to superoxide, hydrogen peroxide, and other reactive species, generated by ‘electron leakage’ from the respiratory chain. The level of oxidative stress to mitochondrial proteins is not constant, but instead varies greatly with numerous metabolic and environmental factors. Oxidized mitochondrial proteins must be removed rapidly (by proteolytic degradation) or they will aggregate, cross-link, and cause toxicity. The Lon Protease is a key enzyme in the degradation of oxidized proteins within the mitochondrial matrix. Under conditions of acute stress Lon is highly inducible, possibly with the oxidant acting as the signal inducer, thereby providing increased protection. It seems that under chronic stress conditions, however, Lon levels actually decline. Lon levels also decline with age and with senescence, and senescent cells even lose the ability to induce Lon during acute stress. We propose that the regulation of Lon is biphasic, in that it is up-regulated during transient stress and down-regulated during chronic stress and aging, and we suggest that the loss of Lon responsiveness may be a significant factor in aging, and in age-related diseases.

133 citations

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TL;DR: This review describes sarcopenia as a muscle-wasting syndrome distinct from other atrophic diseases and summarizes the current view on molecular causes of sarcopenian development as well as open questions provoking further research efforts.

124 citations

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TL;DR: It is suggested that free radicals and related oxidants are but one subset of stressors with which all life forms must cope over their lifespans, and viewed as a component of Adaptive Homeostasis, the Free Radical Theory of Aging appears both viable and robust.

122 citations


Cited by
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Journal ArticleDOI
TL;DR: This work focuses on ROS at physiological levels and their central role in redox signalling via different post-translational modifications, denoted as ‘oxidative eustress’.
Abstract: 'Reactive oxygen species' (ROS) is an umbrella term for an array of derivatives of molecular oxygen that occur as a normal attribute of aerobic life. Elevated formation of the different ROS leads to molecular damage, denoted as 'oxidative distress'. Here we focus on ROS at physiological levels and their central role in redox signalling via different post-translational modifications, denoted as 'oxidative eustress'. Two species, hydrogen peroxide (H2O2) and the superoxide anion radical (O2·-), are key redox signalling agents generated under the control of growth factors and cytokines by more than 40 enzymes, prominently including NADPH oxidases and the mitochondrial electron transport chain. At the low physiological levels in the nanomolar range, H2O2 is the major agent signalling through specific protein targets, which engage in metabolic regulation and stress responses to support cellular adaptation to a changing environment and stress. In addition, several other reactive species are involved in redox signalling, for instance nitric oxide, hydrogen sulfide and oxidized lipids. Recent methodological advances permit the assessment of molecular interactions of specific ROS molecules with specific targets in redox signalling pathways. Accordingly, major advances have occurred in understanding the role of these oxidants in physiology and disease, including the nervous, cardiovascular and immune systems, skeletal muscle and metabolic regulation as well as ageing and cancer. In the past, unspecific elimination of ROS by use of low molecular mass antioxidant compounds was not successful in counteracting disease initiation and progression in clinical trials. However, controlling specific ROS-mediated signalling pathways by selective targeting offers a perspective for a future of more refined redox medicine. This includes enzymatic defence systems such as those controlled by the stress-response transcription factors NRF2 and nuclear factor-κB, the role of trace elements such as selenium, the use of redox drugs and the modulation of environmental factors collectively known as the exposome (for example, nutrition, lifestyle and irradiation).

1,809 citations

Journal ArticleDOI
TL;DR: Recent cumulative data suggest that, without the existence of the immunosenescence/inflamm-aging duo, human longevity would be greatly shortened and it may be more suitable to aim to maintain general homeostasis and function by appropriately improving immune-inflammatory-functions.
Abstract: The immune system is the most important protective physiological system of the organism. It has many connections with other systems and is, in fact, often considered as part of the larger neuro-endocrine-immune axis. Most experimental data on immune changes with aging show a decline in many immune parameters when compared to young healthy subjects. The bulk of these changes is termed immunosenescence. Immunosenescence has been considered for some time as detrimental because it often leads to subclinical accumulation of pro-inflammatory factors and inflamm-aging. Together, immunosenescence and inflamm-aging are suggested to stand at the origin of most of the diseases of the elderly, such as infections, cancer, autoimmune disorders, and chronic inflammatory diseases. However, an increasing number of immune-gerontologists have challenged this negative interpretation of immunosenescence with respect to its significance in aging-related alterations of the immune system. If one considers these changes from an evolutionary perspective, they can be viewed preferably as adaptive or remodeling rather than solely detrimental. Whereas it is conceivable that global immune changes may lead to various diseases, it is also obvious that these changes may be needed for extended survival/longevity. Recent cumulative data suggest that, without the existence of the immunosenescence/inflamm-aging duo (representing two sides of the same phenomenon), human longevity would be greatly shortened. This review summarizes recent data on the dynamic reassessment of immune changes with aging. Accordingly, attempts to intervene on the aging immune system by targeting its rejuvenation, it may be more suitable to aim to maintain general homeostasis and function by appropriately improving immune-inflammatory-functions.

777 citations

01 Jan 1973
TL;DR: The adult respiratory distress syndrome (ARDS) is an important and common medical emergency and is likely to occur in all hospitals dealing in respiratory care as mentioned in this paper, which occurs from a variety of diffuse pulmonary injuries which are either direct or indirect attacks on the lung parenchyma.
Abstract: The adult respiratory distress syndrome (ARDS) is an important and common medical emergency and is likely to occur in all hospitals dealing in respiratory care. The syndrome occurs from a variety of diffuse pulmonary injuries which are either direct or indirect attacks on the lung parenchyma. Once lung damage occurs, exudation of fluid and loss of surfactant activity leads to impaired gas exchange and reduced pulmonary compliance. The syndrome presents clinically as marked respiratory distress, tachypnea, cyanosis, refractory hypoxemia, high inflation pressure requirements during ventilatory support, diffuse alveolar infiltrates on chest roentgenograms and postmortem pulmonary congestion, hyperemia and hyaline membrane formation. Principles of management include adequate support of oxygen transport, ventilation and circulation employing volume respirators with positive end-expiratory pressure (PEEP). During the support phase, further pulmonary injury in terms of fluid overload, oxygen toxicity or infection, must be prevented or treated. When these principles of management are followed, recovery often occurs in spite of severe pulmonary injury as indicated by the first two illustrative cases.

669 citations

Journal ArticleDOI
05 Sep 2018-Nature
TL;DR: Interventions, including changes to lifestyle and medical innovations, are needed to prevent disease and increase late-life health in humans.
Abstract: Longer human lives have led to a global burden of late-life disease However, some older people experience little ill health, a trait that should be extended to the general population Interventions into lifestyle, including increased exercise and reduction in food intake and obesity, can help to maintain healthspan Altered gut microbiota, removal of senescent cells, blood factors obtained from young individuals and drugs can all improve late-life health in animals Application to humans will require better biomarkers of disease risk and responses to interventions, closer alignment of work in animals and humans, and increased use of electronic health records, biobank resources and cohort studies

630 citations

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TL;DR: This review summarizes current studies on age-related impairment of Nrf2/EpRE function and discusses the changes in NRF2 regulatory mechanisms with aging.

570 citations