Human aging and disease: Lessons from age-related macular degeneration

Proceedings of the National Academy of Sciences of the United States of America
Jennings Luu, Krzysztof Palczewski

Abstract

Aging is the most significant risk factor associated with chronic disease in humans. The accumulation of genetic damage throughout life leads to a variety of biological aberrations, including disrupted protein homeostasis, metabolic dysfunction, and altered cellular signaling. Such changes ultimately result in cellular senescence, death, or transformation to uncontrolled proliferation, thereby compromising human health. Events contributing to age-dependent physiological decline also occur in the context of hormonal and metabolic changes, affecting interconnected cellular networks. This complexity often confounds the development of effective treatments for aging and age-related diseases. In contrast to monotherapy and polypharmacology, an innovative systems pharmacology approach can identify synergistic combinations of drugs that modulate distinct mechanistic nodes within a network, minimizing off-target side effects and enabling better therapeutic outcomes. G protein-coupled receptors (GPCRs) are particularly good targets for the application of systems pharmacology, because they activate different signal transduction pathways that can culminate in a common response. Here, we describe a systems pharmacology strategy for the trea...Continue Reading

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Citations

Oct 28, 2018·The British Journal of Ophthalmology·Chikako HaradaTakayuki Harada
Oct 9, 2019·Expert Review of Proteomics·Mohammad Hassan BaigJae-June Dong
Feb 21, 2019·Investigative Ophthalmology & Visual Science·Ying LinJianhua Wang
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Jul 18, 2020·Frontiers in Pharmacology·Peng Zhou, Jun Zhou
Sep 10, 2020·Journal of Ophthalmology·Junyu Zhang, Yu Zhou
Jul 22, 2020·Human Molecular Genetics·Jennings LuuKrzysztof Palczewski
Jan 11, 2020·Computational and Structural Biotechnology Journal·Paula Santos-OtteStuart Maudsley
Nov 15, 2020·The Journal of Biological Chemistry·Philip D Kiser, Krzysztof Palczewski
Jan 13, 2021·The Journal of Biological Chemistry·Philip D Kiser, Krzysztof Palczewski
Nov 18, 2021·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Michael Landowski, Catherine Bowes Rickman

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