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 Free Radical Theory of Aging Matures

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Lysosomal Storage Diseases

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

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Retinal age pigments generated by self-assembling lysosomotropic detergents

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Reducing lipofuscin accumulation and cardiomyocytic senescence of aging heart by enhancing autophagy

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New biomarkers probing depth of cell senescence assessed by laser scanning cytometry

Zhao, H. L., Halicka, H. D., Traganos, F., Jorgensen, E. D., & Darżynkiewicz, Z. (2010) · Cytometry Part A · doi:10.1002/cyto.a.20983 · Cited by 47

Deficiency of insulin-like growth factor 1 attenuates aging-induced changes in hepatic function: Role of autophagy

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Global hypoxia induced impairment in learning and spatial memory is associated with precocious hippocampal aging

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Zinc and Autophagy in Age-Related Macular Degeneration

Błasiak, J., Pawłowska, E., Chojnacki, J., Szczepańska, J., Chojnacki, C. J., & Kaarniranta, K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21144994 · Cited by 50

Genetic disruption of WASHC4 drives endo-lysosomal dysfunction and cognitive-movement impairments in mice and humans

Courtland, J. L., Bradshaw, T. W., Waitt, G., Soderblom, E. J., Ho, T., Rajab, A., Vancini, R., Kim, I. H., & Soderling, S. H. (2021) · eLife · doi:10.7554/elife.61590 · Cited by 49

The Influence of Long-term Mercury Exposure on Selenium Availability in Tissues: An Evaluation of Data

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Protein homeostasis in aging and cancer

Chen, X., Shen, T., Fang, S.-J., Sun, X.-M., Li, G., & Li, Y. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1143532 · Cited by 52

Mechanisms driving the ageing heart

Anderson, R., Richardson, G. D., & Passos, J. F. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.10.015 · Cited by 47

Bisretinoid phospholipid and vitamin A aldehyde: shining a light

Kim, H. J., & Sparrow, J. R. (2020) · Journal of Lipid Research · doi:10.1194/jlr.tr120000742 · Cited by 47

Therapy-Induced Senescence Enhances the Efficacy of HER2-Targeted Antibody–Drug Conjugates in Breast Cancer

Duro-Sánchez, S., Nadal-Serrano, M., Lalinde-Gutiérrez, M., Arenas, E. J., Bernadó Morales, C., Morancho, B., Escorihuela, M., Pérez-Ramos, S., Escrivá-de-Romaní, S., Gandullo-Sánchez, L., et al. (2022) · Cancer Research · doi:10.1158/0008-5472.can-22-0787 · Cited by 45

Age-induced apoptosis in the male genital tract of the mouse

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Amelioration of Age Associated Neuroinflammation on Long Term Bacosides Treatment

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Implications of aging and the endoplasmic reticulum unfolded protein response on the molecular modality of breast cancer

Minakshi, R., Rahman, S., Jan, A. T., Ayyagari, A., & Kim, J. (2017) · Experimental & Molecular Medicine · doi:10.1038/emm.2017.215 · Cited by 45

Is microglial dystrophy a form of cellular senescence? An analysis of senescence markers in the aged human brain

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Catalpol Modulates Lifespan via DAF-16/FOXO and SKN-1/Nrf2 Activation inCaenorhabditis elegans

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Molecular genetic approaches to understanding the roles and regulation of iron in brain health and disease

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4-Hydroxybenzoic acid-mediated lifespan extension in Caenorhabditis elegans

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Multiple Involvement of Oxidative Stress in Werner Syndrome Phenotype

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The impact of specific oxidized amino acids on protein turnover in J774 cells

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The effect of aged microglia on synaptic impairment and its relevance in neurodegenerative diseases

Triviño, J. J., & von Bernhardi, R. (2021) · Neurochemistry International · doi:10.1016/j.neuint.2021.104982 · Cited by 43

Evidence for L‐dopa incorporation into cell proteins in patients treated with levodopa

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Leucine-rich repeat kinase 2 deficiency is protective in rhabdomyolysis-induced kidney injury

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Effect of pre- and postnatal exposure to urban air pollution on myocardial lipid peroxidation levels in adult mice

Damaceno‐Rodrigues, N. R., Veras, M. M., Negri, E. M., Zanchi, A. C., Rhoden, C. R., Saldiva, P. H. N., Dolhnikoff, M., & Caldini, E. T. E. G. (2009) · Inhalation Toxicology · doi:10.3109/08958370902798430 · Cited by 44

BK channel agonist represents a potential therapeutic approach for lysosomal storage diseases

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An antidiabetic polyherbal phytomedicine confers stress resistance and extends lifespan in Caenorhabditis elegans

Rathor, L., Pant, A., Awasthi, H., Mani, D., & Pandey, R. (2016) · Biogerontology · doi:10.1007/s10522-016-9668-2 · Cited by 43

An R-CaMP1.07 reporter mouse for cell-type-specific expression of a sensitive red fluorescent calcium indicator

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The Interaction of Diet and Mitochondrial Dysfunction in Aging and Cognition

Kaliszewska, A., Allison, J., Martini, M., & Arias, N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073574 · Cited by 52

Retinal Photodamage by Endogenous and Xenobiotic Agents†

Wielgus, A. R., & Roberts, J. E. (2012) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2012.01174.x · Cited by 44

The influence of sedimentation on metal accumulation and cellular oxidative stress markers in the Antarctic bivalve Laternula elliptica

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Disturbances in the control of capillary flow in an aged APPswe/PS1ΔE9 model of Alzheimer's disease

Gutiérrez‐Jiménez, E., Angleys, H., Rasmussen, P. M., West, M. J., Catalini, L., Iversen, N., Jensen, M. S., Frische, S., & Østergaard, L. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.10.006 · Cited by 44

Baseline Predictors of Visual Acuity Outcome in Patients with Wet Age-Related Macular Degeneration

Zhang, X., & Lai, T. Y. Y. (2018) · BioMed Research International · doi:10.1155/2018/9640131 · Cited by 43

Quantification of Ceroid and Lipofuscin in Skeletal Muscle

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Anti-oxidative cellular protection effect of fasting-induced autophagy as a mechanism for hormesis

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Inhibition or Stimulation of Autophagy Affects Early Formation of Lipofuscin-Like Autofluorescence in the Retinal Pigment Epithelium Cell

Lei, L., Tzekov, R. T., Li, H., McDowell, J. H., Gao, G., Smith, W. C., Tang, S., & Kaushal, S. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18040728 · Cited by 40

Lipofuscin Generated by UVA Turns Keratinocytes Photosensitive to Visible Light

Tonolli, P. N., Chiarelli-Neto, O., Santacruz-Pérez, C., Junqueira, H. C., Watanabe, I., Ravagnani, F. G., Martins, W. K., & Baptista, M. S. (2017) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2017.06.018 · Cited by 40

Oral administration of Grifola frondosa polysaccharides improves memory impairment in aged rats via antioxidant action

Chen, Z., Tang, Y., Liu, A., Jin, X., Zhu, J., & Lu, X. (2017) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201700313 · Cited by 41

Alleviation of Senescence via ATM Inhibition in Accelerated Aging Models.

Kuk, M. U., Kim, J., Lee, Y., Cho, K. A., Park, J. T., & Park, S. C. (2019) · Europe PMC (PubMed Central) · doi:10.14348/molcells.2018.0352 · Cited by 41

Differences in copper bioaccumulation and biological responses in three Mytilus species

Brooks, S., Farmen, E., Heier, L. S., Blanco-Rayón, E., & Izagirre, U. (2014) · Aquatic Toxicology · doi:10.1016/j.aquatox.2014.12.018 · Cited by 42

Collagen XVII: A Shared Antigen in Neurodermatological Interactions?

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Modulation of age‐related changes in oxidative stress markers and energy status in the rat heart and hippocampus: a significant role for ozone therapy

El‐Sawalhi, M. M., Darwish, H. A., Mausouf, M. N., & Shaheen, A. A. (2012) · Cell Biochemistry and Function · doi:10.1002/cbf.2930 · Cited by 40

Oxidized protein aggregates: Formation and biological effects

Grune, T. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.02.014 · Cited by 45

Formation of a combined Ca/Cd toxicity on lifespan of nematode Caenorhabditis elegans

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3-Ketoacyl thiolase delays aging of Caenorhabditis elegans and is required for lifespan extension mediated by sir-2.1

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mTOR Kinase and the Regulatory Subunit of Protein Kinase A (PRKAR1A) Spatially and Functionally Interact during Autophagosome Maturation

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Peptides from sesame cake extend healthspan of Caenorhabditis elegans via upregulation of skn-1 and inhibition of intracellular ROS levels

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Identification of senescent cells in multipotent mesenchymal stromal cell cultures: Current methods and future directions

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Relation of Plasma Selenium and Lipid Peroxidation End Products in Patients With Alzheimer’s Disease

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Adaptations of the antioxidant system in erythrocytes of trained adult rats: Impact of intermittent hypobaric-hypoxia at two altitudes

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History and Morphology of the Lysosome

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Effect of Cell Age on Uptake and Toxicity of Nanoparticles: The Overlooked Factor at the Nanobio Interface

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Evidence for postnatal neurogenesis in the human amygdala

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Ultrastructure of testicular macrophages in aging mice

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Banji, D., Banji, O. J. F., Dasaroju, S., & Annamalai, A. R. (2012) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2012.11.018 · Cited by 37

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Involvement of lysosomal storage-induced p38 MAP kinase activation in the overproduction of nitric oxide by microglia in cathepsin D-deficient mice

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Medical bioremediation: Prospects for the application of microbial catabolic diversity to aging and several major age-related diseases

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A Sequential Study of Age-Related Lipofuscin Accumulation in Hippocampus and Striate Cortex of Rats

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Bisretinoids of the Retina: Photo-Oxidation, Iron-Catalyzed Oxidation, and Disease Consequences

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Deacidification of endolysosomes by neuronal aging drives synapse loss

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The effect of lead-induced oxidative stress on blood viscosity and rheological properties of erythrocytes in lead exposed humans

Kasperczyk, A., Słowińska-Łożyńska, L., Dobrakowski, M., Zalejska–Fiolka, J., & Kasperczyk, S. (2014) · Clinical Hemorheology and Microcirculation · doi:10.3233/ch-131678 · Cited by 35

Transient acceleration of autophagic degradation by pharmacological Nrf2 activation is important for retinal pigment epithelium cell survival

Saito, Y., Kuse, Y., Inoue, Y., Nakamura, S., Hara, H., & Shimazawa, M. (2018) · Redox Biology · doi:10.1016/j.redox.2018.09.004 · Cited by 35

Physiological and pathological functions of LRRK2: implications from substrate proteins

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Motoneuron deafferentation and gliosis occur in association with neuromuscular regressive changes during ageing in mice

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Autofluorescence Spectroscopy for Monitoring Metabolism in Animal Cells and Tissues

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Genetic Regulation of Caenorhabditis elegans Lysosome Related Organelle Function

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Metabolic, immune, epigenetic, endocrine and phenotypic abnormalities found in individuals with autism spectrum disorders, Down syndrome and Alzheimer disease may be caused by congenital and/or acquired chronic cerebral toxoplasmosis

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Reduced Expression of Lipoic Acid Synthase Accelerates Diabetic Nephropathy

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Mitochondrial Autophagy and Lipofuscin Accumulation in Aging Odontoblasts

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Pathological reactions and recovery of hepatopancreatic digestive cells from the marine snail Littorina littorea following exposure to a polycyclic aromatic hydrocarbon

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GC/MS analysis of thermally degraded neuromelanin from the human substantia nigra

Dzierżęga‐Lęcznar, A., Kurkiewicz, S., Stȩpień, K. B., Chodurek, E., Wilczok, T., Arzberger, T., Riederer, P. F., & Gerlach, M. (2004) · Journal of the American Society for Mass Spectrometry · doi:10.1016/j.jasms.2004.03.009 · Cited by 34

Oxidative Damage to Proteins

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Identification ofCaenorhabditis elegansGenes Regulating Longevity Using Enhanced RNAi-sensitive StrainsPreprint

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In situ estimation of the entire color and spectra of age pigment-like materials: Application of a front-surface 3D-fluorescence technique

LI, G., LIAO, Y., Wang, X., SHENG, S., & Yin, D. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2005.12.008 · Cited by 33

Automated Processing of Imaging Data through Multi-tiered Classification of Biological Structures Illustrated Using Caenorhabditis elegans

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Inhibiting effects of dietary polyphenols on chronic eye diseases

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Transgenerational reproductive and developmental toxicity of tebuconazole in Caenorhabditis elegans

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Lipofuscin Hypothesis of Alzheimer’s Disease

Giaccone, G., Orsi, L., Cupidi, C., & Tagliavini, F. (2011) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000329544 · Cited by 37

A crucial role of ROCK for alleviation of senescence-associated phenotype

Park, J. T., Kang, H. T., Park, C., Lee, Y., Cho, K. A., & Park, S. C. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2018.02.012 · Cited by 33

Autofluorescence: A potential pitfall in immunofluorescence-based inflammation grading

Wizenty, J., Ashraf, M., Rohwer, N., Stockmann, M., Weiß, S., Biebl, M., Pratschke, J., Aigner, F., & Wuensch, T. (2018) · Journal of Immunological Methods · doi:10.1016/j.jim.2018.02.007 · Cited by 33

Impact of aging on heat shock protein expression in the substantia nigra and striatum of the female rat

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Generation of a neurodegenerative disease mouse model using lentiviral vectors carrying an enhanced synapsin I promoter

Matsuzaki, Y., Oue, M., & Hirai, H. (2013) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2013.12.004 · Cited by 32

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Death rates reflect accumulating brain damage in arthropods

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Added value of infrared, red-free and autofluorescence fundus imaging in pseudoxanthoma elasticum

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Design, Synthesis, Nematicidal Activity, and Mechanism of Novel Amide Derivatives Containing an 1,2,4-Oxadiazole Moiety

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Retinal Pigment Epithelium Under Oxidative Stress: Chaperoning Autophagy and Beyond

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Anti-aging properties of Ribes fasciculatum in Caenorhabditis elegans.

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Salidroside mediated stabilization of Bcl -xL prevents mitophagy in CA3 hippocampal neurons during hypoxia

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Multiparameter flow cytometric detection and quantification of senescent cells in vitro

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A role for 4-hydroxy-2-nonenal in premature placental senescence in preeclampsia and intrauterine growth restriction

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Effect of the tocotrienol-rich fraction on the lifespan and oxidative biomarkers in Caenorhabditis elegans under oxidative stress

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Genome-wide microarray analysis of brain gene expression in mice on a short-term high iron diet

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The effect of manganese exposure in Atp13a2-deficient mice

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Environmental stress impairs photoreceptor outer segment (POS) phagocytosis and degradation and induces autofluorescent material accumulation in hiPSC-RPE cells

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Lipofuscin

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Lipofuscin: Mechanisms of formation and increase with age

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Lipofuscinogenesis in a model system of cultured cardiac myocytes

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Free radicals in cellular pathology : Mechanisms behind lipofucin formation in cultured myocardial cells

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The age pigment lipofuscin causes oxidative stress, lysosomal dysfunction, and pyroptotic cell death

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