Lipofuscin: mechanisms of age-related accumulation and influence on cell function12 1Guest Editor: Rajindar S. Sohal 2This article is part of a series of reviews on “Oxidative Stress and Aging.” The full list of papers may be found on the homepage of the journal.

Aging: a theory based on free radical and radiation chemistry

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The lipofuscin fluorophore A2E mediates blue light-induced damage to retinal pigmented epithelial cells.

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Involvement of the Endosomal-Lysosomal System Correlates With Regional Pathology in Creutzfeldt-Jakob Disease

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Survival of Retinal Pigment Epithelium after Exposure to Prolonged Oxidative Injury: A Detailed Gene Expression and Cellular Analysis

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Grape seed proanthocyanidin lowers brain oxidative stress in adult and middle-aged rats

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Emerging roles of microglial cathepsins in neurodegenerative disease

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Ginsenoside Prolongs the Lifespan of C. elegans via Lipid Metabolism and Activating the Stress Response Signaling Pathway

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Effects of resveratrol on longevity, cognitive ability and aging-related histological markers in the annual fish Nothobranchius guentheri

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Influence of Normal Aging on Brain Autophagy: A Complex Scenario

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The ocular surface immune system through the eyes of aging

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Αlpha-Synuclein as a Mediator in the Interplay between Aging and Parkinson’s Disease

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Cellular senescence in the aging brain: A promising target for neurodegenerative diseases

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Age-Related Changes in d-Aspartate Oxidase Promoter Methylation Control Extracellular d-Aspartate Levels and Prevent Precocious Cell Death during Brain Aging

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Aging Dilates Atrium and Pulmonary Veins

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Comparison of the Aerobic Photoreactivity of A2E with its Precursor Retinal¶

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Green tea averts age-dependent decline of hippocampal signaling systems related to antioxidant defenses and survival

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The value of muscle biopsies in Pompe disease: identifying lipofuscin inclusions in juvenile- and adult-onset patients

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Rosmarinic acid improved antioxidant properties and healthspan via the IIS and MAPK pathways in Caenorhabditis elegans

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Polysaccharide extracted from the leaves of Cyclocarya paliurus (Batal.) Iljinskaja enhanced stress resistance in Caenorhabditis elegans via skn-1 and hsf-1

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Impaired Cargo Clearance in the Retinal Pigment Epithelium (RPE) Underlies Irreversible Blinding Diseases

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Age-Related Markers Assayed at Different Developmental Stages of the Annual Fish Nothobranchius rachovii

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Exposure to Polystyrene Nanoplastics Led to Learning and Memory Deficits in Zebrafish by Inducing Oxidative Damage and Aggravating Brain Aging

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Irradiation With Carbon Ion Beams Induces Apoptosis, Autophagy, and Cellular Senescence in a Human Glioma-Derived Cell Line

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Chapter Thirty‐Three Lysosomes and Autophagy in Aquatic Animals

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Influence of age on aluminum induced lipid peroxidation and neurolipofuscin in frontal cortex of rat brain: A behavioral, biochemical and ultrastructural study

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Autophagic Activity and Aging in Human Odontoblasts

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Testing the ?garbage? accumulation theory of ageing: mitotic activity protects cells from death induced by inhibition of autophagy

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Role of Oxidative Stress in Peroxisome Proliferator-Mediated Carcinogenesis

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Lipofuscin is formed independently of macroautophagy and lysosomal activity in stress-induced prematurely senescent human fibroblasts

Höhn, A., Sittig, A., Jung, T., Grimm, S., & Grune, T. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.08.591 · Cited by 64

Abnormal Intracellular Accumulation and Extracellular Aβ Deposition in Idiopathic and Dup15q11.2-q13 Autism Spectrum Disorders

Węgiel, J., Frackowiak, J., Mazur‐Kolecka, B., Schanen, N. C., Cook, E. H., Sigman, M., Brown, W. T., Kuchna, I., Wegiel, J., Nowicki, K., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035414 · Cited by 65

Characterization of skn-1/wdr-23 phenotypes in Caenorhabditis elegans; pleiotrophy, aging, glutathione, and interactions with other longevity pathways

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Oxidation and Antioxidation of Natural Products in the Model Organism Caenorhabditis elegans

Zhu, A., Zheng, F., Zhang, W., Li, L., Li, Y., Hu, H., Wu, Y., Bao, W., Li, G., Wang, Q., et al. (2022) · Antioxidants · doi:10.3390/antiox11040705 · Cited by 68

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Rescue of Compromised Lysosomes Enhances Degradation of Photoreceptor Outer Segments and Reduces Lipofuscin-Like Autofluorescence in Retinal Pigmented Epithelial Cells

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Caloric restriction and the precision-control of autophagy: A strategy for delaying neurodegenerative disease progression

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Activation of Autophagy Ameliorates Cardiomyopathy in Mybpc3 -Targeted Knockin Mice

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Iron homeostasis in the brain: complete iron regulatory protein 2 deficiency without symptomatic neurodegeneration in the mouse

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Lipofuscin-like pigments in the rat heart during early postnatal development: effect of selenium supplementation

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Pantothenate Rescues Iron Accumulation in Pantothenate Kinase-Associated Neurodegeneration Depending on the Type of Mutation

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Glutathione-peroxidase-1 null muscle progenitor cells are globally defective

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Chronic green tea consumption prevents age-related changes in rat hippocampal formation

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Autolysosomes accumulate during in vitro CD8+ T-lymphocyte aging and may participate in induced death sensitization of senescent cells

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Apolipoprotein E and its role in aging and survival

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High NaCl Promotes Cellular Senescence

Dmitrieva, N. I., & Burg, M. B. (2007) · Cell Cycle · doi:10.4161/cc.6.24.5084 · Cited by 59

Functional Analysis of Lysosomes During Mouse Preimplantation Embryo Development

Tsukamoto, S., Hara, T., Yamamoto, A., Ohta, Y., Ayako, W. A. D. A., Ishida, Y., Kito, S., Nishikawa, T., Minami, N., Sato, K., et al. (2012) · Journal of Reproduction and Development · doi:10.1262/jrd.2012-096 · Cited by 59

Inhibition of cathepsins and related proteases by amino acid, peptide, and protein hydroperoxides

Headlam, H. A., Gracanin, M., Rodgers, K. J., & Davies, M. J. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.12.036 · Cited by 59

Advanced Atherosclerotic Foam Cell Formation Has Features of an Acquired Lysosomal Storage Disorder

Jerome, W. G. (2006) · Rejuvenation Research · doi:10.1089/rej.2006.9.245 · Cited by 59

In vivo calcium imaging of the aging and diseased brain

Eichhoff, G., Busche, M. A., & Garaschuk, O. (2008) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-007-0709-6 · Cited by 59

Targeting Immune Senescence in Atherosclerosis

Vellasamy, D. M., Lee, S.-J., Goh, K. W., Goh, B. H., Tang, Y.-Q., Ming, L. C., & Yap, W. H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113059 · Cited by 63

Red wine antioxidants protect hippocampal neurons against ethanol-induced damage: A biochemical, morphological and behavioral study

Assunção, M., Santos‐Marques, M. J., de Freitas, V. A. P., Carvalho, F. D., Andrade, J. P., Lukoyanov, N., & Paula-Barbosa, M. M. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.03.040 · Cited by 57

Quantitative evaluation of the beneficial effects in the mdx mouse of epigallocatechin gallate, an antioxidant polyphenol from green tea

Nakae, Y., Dorchies, O. M., Stoward, P. J., Zimmermann, B. F., Ritter, C., & Rüegg, U. T. (2012) · Histochemistry and Cell Biology · doi:10.1007/s00418-012-0926-3 · Cited by 58

Observation of Human Retinal Remodeling in Octogenarians with a Resveratrol Based Nutritional Supplement

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Lipofuscin-like autofluorescence within microglia and its impact on studying microglial engulfment

Stillman, J. M., Lopes, F. M., Lin, J., Hu, K., Reich, D. S., & Schafer, D. P. (2023) · Nature Communications · doi:10.1038/s41467-023-42809-y · Cited by 61

Pattern of lipofuscin pigmentation in nitrergic and non-nitrergic, neurofilament immunoreactive myenteric neuron types of human small intestine

Brehmer, A., Blaser, B., Seitz, G., Schroedl, F., & Neuhuber, W. (2004) · Histochemistry and Cell Biology · doi:10.1007/s00418-003-0603-7 · Cited by 57

What have we learned on aging from omics studies?

Cellerino, A., & Ori‬‬, A. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.06.012 · Cited by 59

Role of mTOR in autophagic and lysosomal reactions to environmental stressors in molluscs

Sforzini, S., Moore, M. N., Oliveri, C., Volta, A., Jha, A. N., Bannı, M., & Viarengo, A. (2017) · Aquatic Toxicology · doi:10.1016/j.aquatox.2017.12.014 · Cited by 57

Upregulation of APP endocytosis by neuronal aging drives amyloid-dependent synapse loss

Burrinha, T., Martinsson, I., Gomes, R., Terrasso, A. P., Gouras, G. K., & Almeida, C. G. (2021) · Journal of Cell Science · doi:10.1242/jcs.255752 · Cited by 64

Examining the proteins of functional retinal lipofuscin using proteomic analysis as a guide for understanding its origin.

Warburton, S., Southwick, K., Hardman, R. M., Secrest, A. M., Grow, R. K., Xin, H., Woolley, A. T., Burton, G. F., & Thulin, C. D. (2005) · PubMed · Cited by 57

Stargardt macular dystrophy and evolving therapies

Hussain, R. M., Ciulla, T. A., Berrocal, A. M., Gregori, N. Z., Flynn, H. W., & Lam, B. L. (2018) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2018.1513486 · Cited by 56

Possibility of mixed progenitor cells in sea star arm regeneration

Hernroth, B. E., Farahani, F., Brunborg, G., Dupont, S., Dejmek, A., & Sköld, H. N. (2010) · Journal of Experimental Zoology Part B Molecular and Developmental Evolution · doi:10.1002/jez.b.21352 · Cited by 55

TFEB ameliorates the impairment of the autophagy-lysosome pathway in neurons induced by doxorubicin

Moruno-Manchon, J. F., Uzor, N.-E., Kesler, S. R., Wefel, J. S., Townley, D. M., Nagaraja, A. S., Pradeep, S., Mangala, L. S., Sood, A. K., & Tsvetkov, A. S. (2016) · Aging · doi:10.18632/aging.101144 · Cited by 61

Genomic aspects of age-related macular degeneration

Horie‐Inoue, K., & Inoue, S. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.08.013 · Cited by 54

Antioxidant and anti-aging potential of Juniper berry ( Juniperus communis L.) essential oil in Caenorhabditis elegans model system

Pandey, S., Tiwari, S., Kumar, A., Niranjan, A., Chand, J., Lehri, A., & Chauhan, P. S. (2018) · Industrial Crops and Products · doi:10.1016/j.indcrop.2018.04.066 · Cited by 58

Non-viral Gene Therapy for Stargardt Disease with ECO/pRHO-ABCA4 Self-Assembled Nanoparticles

Sun, D., Schur, R. M., Sears, A. E., Gao, S., Vaidya, A. M., Sun, W., Maeda, A., Kern, T. S., Palczewski, K., & Lu, Z. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.09.010 · Cited by 57

Human and rat brain lipofuscin proteome

Ottis, P., Koppe, K., Onisko, B., Dynin, I. C., Arzberger, T., Kretzschmar, H. A., Requena, J. R., Silva, C. J., Huston, J. P., & Korth, C. (2012) · PROTEOMICS · doi:10.1002/pmic.201100668 · Cited by 55

Multicellular models of Friedreich ataxia

Puccio, H. M. (2009) · Journal of Neurology · doi:10.1007/s00415-009-1004-1 · Cited by 58

Beyond starvation: An update on the autophagic machinery and its functions

Kawabata, T., & Yoshimori, T. (2015) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2015.12.005 · Cited by 56

Regulation of Lysosomal Function by the DAF-16 Forkhead Transcription Factor Couples Reproduction to Aging in Caenorhabditis elegans

Baxi, K., Ghavidel, A., Waddell, B. M., Harkness, T. A. A., & de Carvalho, C. E. (2017) · Genetics · doi:10.1534/genetics.117.204222 · Cited by 54

Role of autophagy in environmental neurotoxicity

Pellacani, C., & Costa, L. G. (2018) · Environmental Pollution · doi:10.1016/j.envpol.2017.12.102 · Cited by 53

Transplant of microbiota from long-living people to mice reduces aging-related indices and transfers beneficial bacteria

Chen, Y., Zhang, S., Zeng, B., Zhao, J., Yang, M., Zhang, M., Li, Y., Ni, Q., Wu, D., & Li, Y. (2020) · Aging · doi:10.18632/aging.102872 · Cited by 54

A2E and Lipofuscin

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Chronic green tea catechins administration prevents oxidative stress-related brain aging in C57BL/6J mice

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