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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Engineered nanoparticles (ENPs): applications, risk assessment, and risk management in the agriculture and food sectors

Ovissipour, M., Syamaladevi, R. M., Rasco, B., & Sablani, S. S. (2014) · doi:10.1002/9781118488553.ch7 · Cited by 5

The Lysosome in Aging‐Related Neurodegenerative Diseases

Nixon, R. A. (2016) · Wiley eBooks · doi:10.1002/9781118978320.ch9 · Cited by 5

JNK signal-driven histone methylations mediate transgenerational neurotoxicity of 6-PPD Quinone at predicted environmental concentrations in Caenorhabditis elegans

Tan, X., Cao, J., Chang, L., Huang, J., Yang, X., Wu, Y., Wang, D., & Liu, H. (2025) · Environmental Chemistry and Ecotoxicology · doi:10.1016/j.enceco.2025.10.018 · Cited by 4

Temozolomide-induced senescent glioblastoma cells acquire sensitivity to TRAIL death receptor 5-mediated apoptosis

Isakova, A. A., Mazur, D. V., Антипова, Н. В., Николаевна, Д. И., Mozherov, A. M., Krasnov, K. S., Фадеев, Р. С., Kirpichnikov, M. P., Gasparian, M. E., & Yagolovich, A. V. (2025) · Medical Oncology · doi:10.1007/s12032-025-03130-4 · Cited by 4

Multi-modal label-free imaging of cellular metabolism and oxidative stress in 3D brain tissue models

Zhang, Y., Savvidou, M. G., Liaudanskaya, V., Ramanathan, V., Bui, T. T., Lindley, M., Fu, Y., Sze, A., Ugwu, U. O., Dilsizian, M. E., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-09122-4 · Cited by 5

Evaluating the reproductive status of the male budgerigar (Melopsittacus undulatus)

Reitemeier, S., Hänse, M., Hahn, A., Schmidt, V., Steinbach-Sobiraj, K., Krautwald‐Junghanns, M., & Einspanier, A. (2011) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2011.02.028 · Cited by 4

Acetaldehyde

Rajendram, R., Rajendram, R., & Preedy, V. R. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800213-1.00051-1 · Cited by 6

Verification of ageing methods for the burrowing shrimp, Neotrypaea californiensis, using extractable lipofuscin and gastric mill cuticular features

Bosley, K. M., Coleman, N., & Dumbauld, B. R. (2019) · Journal of the Marine Biological Association of the United Kingdom · doi:10.1017/s0025315419000742 · Cited by 4

Impact of alpha-tocopherol deficiency and supplementation on sacrocaudalis and gluteal muscle fiber histopathology and morphology in horses

Bookbinder, L. C., Finno, C. J., Firshman, A. M., Katzman, S. A., Burns, E., Peterson, J. A. M., Dahlgren, A. R., Ming-Whitfield, B., Glessner, S., Matsui, A. K. B., et al. (2019) · Journal of Veterinary Internal Medicine · doi:10.1111/jvim.15643 · Cited by 4

Ameliorative Action of Mn-Salen Derivatives on CCl4-Induced Destructive Effects and Lipofuscin-Like Pigment Formation in Rats’ Liver and Brain: Post-Treatment of Young Rats with EUKs

Meftah, S., Yazdanparast, R., & Molaei, M. (2014) · CellBio · doi:10.4236/cellbio.2014.33010 · Cited by 4

Validation and quantification of extractable age pigments for determining the age of Antarctic krill (Euphausia superba)

McGaffin, A. F., Nicol, S., Virtue, P., Hirano, Y., Matsuda, T., Uchida, I., Candy, S. G., & Kawaguchi, S. (2011) · Marine Biology · doi:10.1007/s00227-011-1688-5 · Cited by 4

Effects of contaminant exposure and food restriction on hepatic autophagic lysosomal parameters in Herring Gull (Larus argentatus) chicks

Hegseth, M. N., Gorbi, S., Bocchetti, R., Camus, L., Gabrielsen, G. W., & Regoli, F. (2014) · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology · doi:10.1016/j.cbpc.2014.04.006 · Cited by 4

Mitochondrial Lipofuscin and Thermomitochondrial Lipofuscin in Homogenates of Rat Organs

Chaplygina, A. V., & Vekshin, N. L. (2019) · BIOPHYSICS · doi:10.1134/s0006350919010044 · Cited by 4

Alterations of Neuronal Lysosomes in Alzheimer’s Disease and in APPxPS1-KI Mice

Androuin, A., Thierry, M., Boluda, S., Baskaran, A., Langui, D., Duyckaerts, C., Potier, M., Hachimi, K. E., Delatour, B., & Marty, S. (2022) · Journal of Alzheimer's Disease · doi:10.3233/jad-215692 · Cited by 4

Gonadal Rejuvenation of Mice by Growth Differentiation Factor 11

Zhou, Y., Ni, S., Li, C., Song, L., & Zhang, S. (2021) · The Journals of Gerontology Series A · doi:10.1093/gerona/glab343 · Cited by 4

Effect of starvation and hibernation on the values of five biomarkers of general and specific stress using the land snail Eobania vermiculata

Moschovaki-Filippidou, F., Itziou, A., & Dimitriadis, V. K. (2013) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/j.cbpb.2013.05.004 · Cited by 4

Regulation of neurogenesis in the aging vertebrate brain: role of oxidative stress and neuropsychiatric factors

Kim, E., Shirvalkar, P. R., & Herrera, D. G. (2003) · Clinical Neuroscience Research · doi:10.1016/s1566-2772(03)00005-7 · Cited by 4

Research Progress on Aging Mechanisms

Wang, Q., Zhou, F., Xie, W., Zhao, X., & Liu, X. (2016) · Advances in Aging Research · doi:10.4236/aar.2016.52005 · Cited by 4

IMMUNOLOCALIZATION OF INHIBIN/ACTIVIN SUBUNITS AND STEROIDOGENIC ENZYMES IN THE TESTES OF AN ADULT AFRICAN ELEPHANT (LOXODONTA AFRICANA)

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In Vivo Ca2+ Imaging of the Living Brain Using Multi-cell Bolus Loading Technique

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Gerontology

Anver, M. R., & Haines, D. C. (2004) · Elsevier eBooks · doi:10.1016/b978-012336425-8/50074-1 · Cited by 4

Aging in Marine Animals

Philipp, E. E. R., Strahl, J., & Sukhotin, A. A. (2011) · doi:10.1002/9781444345988.ch14 · Cited by 4

Protein Oxidation and Aging: Different Model Systems and Affecting Factors

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Neuronal aging potentiates beta-amyloid generation via amyloid precursor protein endocytosisPreprint

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Lysosomes cell autonomously regulate myeloid cell states and immune responses

Tejwani, L., Balak, C., Skuja, L. L., Tatarakis, D., Rana, A., Fitzgerald, G. A., Ha, C., Lunkes de Melo, G., Sun, E. W., Heffner, C. M., et al. (2024) · doi:10.1101/2024.11.11.623074 · Cited by 4

Anti-aging potential of caffeoyl-spermidine derivatives from Lycium ruthenicum Murr.: insights from UPLC-QTOF-MS/MS, Caenorhabditis elegans , and mechanistic studies

Shen, L., Zhang, Y., Ran, M., Ren, L., Fu, X., Fang, S., & Liang, X. (2025) · Food & Function · doi:10.1039/d5fo04125b · Cited by 3

Rare genetic diseases associated with G-quadruplex-induced replication stress

Herr, L. M., Mukhopadhyay, S., Anderson, O. M., Couch, T. H., Jones, C. M., Brosh, R. M., & Rossi, M. S. (2026) · Communications Biology · doi:10.1038/s42003-026-09966-4 · Cited by 4

From molecular damage to regulatory constraint: epigenetic and metabolic limits of cellular plasticity in aging

Godlewski, A., & Dziaman, T. (2026) · Frontiers in Aging · doi:10.3389/fragi.2026.1872180 · Cited by 4

Critical factors for flow cytometry analysis of the brain

Sadakata, M., Konno, A., Takase, A., Kasamatsu, T., Iijima, T., Hirai, H., & Sadakata, T. (2025) · FEBS Journal · doi:10.1111/febs.70063 · Cited by 4

The homozygous LRRK2.p.N1437D point mutation mouse is a novel model of parkinsonism

Gan, L., Sun, Y., Zhou, X., Qi, Z.-Y., Liu, F., Tang, Y., Yu, W., Xiao, B., Wang, J., & Wu, J. (2025) · npj Parkinson s Disease · doi:10.1038/s41531-025-00905-4 · Cited by 3

AG86 Peptide-modified Reactive Oxygen Species-responsive Polymer Nanovesicles for Transdermal Delivery of Hydrophilic Ergothioneine to Basal Keratinocytes

Chen, J., Long, Y., Zhou, X., & Yin, Z. (2025) · AAPS PharmSciTech · doi:10.1208/s12249-025-03122-7 · Cited by 3

Xanthophylls and the Eye

Bartlett, H. E. (2013) · Springer eBooks · doi:10.1007/978-3-642-22144-6_166 · Cited by 3

A study on analyzing the terms describing anti-aging effects in Dongeuibogam to propose the methodology for selecting medicinal herbs related to anti-aging effects

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Identification of Atypical Peri-Nuclear Multivesicular Bodies in Oxidative and Glycolytic Skeletal Muscle of Aged and Pompe's Disease Mouse Models

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Stem Cell Aging

Rožman, P. J., Jazbec, K., & Jež, M. (2018) · InTech eBooks · doi:10.5772/intechopen.71764 · Cited by 4

Neurodegenerative Diseases and the Aging Brain

Godin, S. K., Seo, J., & Tsai, L. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811304-2.00017-1 · Cited by 3

Mechanisms of Cell Death

Arnhold, J. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816388-7.00005-x · Cited by 3

Low-intensity whole-body oxidative stress in patients withparotid gland tumors

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Photo-and thermo-regulation by photonic crystals for extended longevity of C. elegans

Yu, S., Shao, Y.-T., Qiu, Q., Cheng, Y., Qing, R., Wang, C., Chen, S., & Chen, X. (2023) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2023.111819 · Cited by 3

Triple enzymatic immunochemistry for interneuron populations in postmortem human cerebral cortex

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Organophospate-Induced Pathology: Mechanisms of Development, Principles of Therapy and Features of Experimental Studies

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Histochemical characteristics and distribution of lipofuscin and polyglucosan bodies in the brain of dogs more than 10 years old

Nešić, S., Vučićević, I., Marinković, D., Kukolj, V., Aničić, M., Ristoski, T., Nikolic, S., & Aleksić‐Kovačević, S. (2021) · Veterinarski glasnik · doi:10.2298/vetgl201002001n · Cited by 3

Retinal Fundus Imaging in Mouse Models of Retinal Diseases

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Autophagy, the “Master” Regulator of Cellular Quality Control: What Happens when Autophagy Fails?

Raquel, A., Catarina, R. A., & Morais, S. (2013) · InTech eBooks · doi:10.5772/55196 · Cited by 4

Aging and Lysosomal Degradation of Cellular Constituents

Terman, A., & Brunk, U. T. (2003) · Springer eBooks · doi:10.1007/978-94-017-0667-4_15 · Cited by 3

Marcadores inmunológicos de envejecimiento

Alonso‐Fernández, P., & la Fuente, M. D. (2008) · Revista Española de Geriatría y Gerontología · doi:10.1016/s0211-139x(08)71177-6 · Cited by 3

Optical coherence tomography in adult-onset vitelliform dystrophy

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Animal Models for Photodiagnosis and Photodynamic Therapy

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A RAPID PLATFORM TO GENERATE LIPOFUSCIN AND SCREEN THERAPEUTIC DRUGS FOR EFFICACY IN LIPOFUSCIN REMOVAL

Gaspar, J., Mathieu, J., & Alvarez, P. J. J. (2016) · Materials, methods & technologies · Cited by 3

The effects of retinoic acid on mmp-2 production, proliferation and ultrastructural morphology in rat uterus

Kotil, T., Şentürk, Ş., Sarıoğlu, T., & Tapul, L. (2017) · Experimental and Toxicologic Pathology · doi:10.1016/j.etp.2017.06.002 · Cited by 3

Probing the in Vivo Relevance of Oxidative Stress in Aging Using Knockout and Transgenic Mice

Müller, F. L., Mele, J., Remmen, H. V., & Richardson, A. G. (2003) · Springer eBooks · doi:10.1007/978-94-017-0667-4_10 · Cited by 3

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Wang, G., Li, L., Liao, X., Wang, S., Mitchell, J. W., Rabel, R. A. C., Luo, S., Shi, J., Sorrells, J. E., Iyer, R. R., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.01.26.577383 · Cited by 3

Polysialic acid is a versatile marker for retinal Müller glia in common vertebrate model organisms and systemsPreprint

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Zuogui and Yougui pills extend lifespan and improve ageing biomarkers via kaempferol-mediated mitophagy in Caenorhabditis elegans

Chen, W., Liu, S., Xu, G., Liu, X., Shi, Y., Wang, G., Ning, Y., Lu, Z., Cao, Y., & Zhao, Y. (2025) · Biogerontology · doi:10.1007/s10522-025-10317-9 · Cited by 3

Dietary phenolic compounds as modulators of AGEs-induced photo-oxidation: A focus on the skin and eye lens

Ávila, F., Fuentealba, D., Muñoz, F., Martín, A. S., & Friguet, B. (2025) · Redox Biochemistry and Chemistry · doi:10.1016/j.rbc.2025.100068 · Cited by 2

Corylin promotes longevity in Caenorhabditis elegans through DAF-16 and SKN-1 coordinated activation of autophagy-mitochondrial homeostasis axis

Shi, F.-Y., Li, C., Zhang, X.-Y., Ou, L., Wu, G.-S., & Luo, H. (2026) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2026.121416 · Cited by 2

Protein oxidation in crowded environments

Fuentes-Lemus, E. (2026) · Biochemical Journal · doi:10.1042/bcj20250150 · Cited by 2

Resilience to Cardiac Aging in Greenland Shark Somniosus microcephalus

Chiavacci, E., Steffensen, K. F., Delaroche, P., Astoricchio, E., Poulsen, A. B., Brayson, D., Garibaldi, F., Lanteri, L., Pinali, C., VALENTE, G. R., et al. (2026) · Aging Cell · doi:10.1111/acel.70505 · Cited by 2

Fasting requires Peroxiredoxin 2 and Peroxiredoxin 6 to coordinate redox dependent mitochondrial and lipid remodelling in Caenorhabditis elegans

Li, P., Zheng, Y., Casas-Martinez, J. C., Xia, Q., Miranda‐Vizuete, A., Goljanek‐Whysall, K., & McDonagh, B. (2026) · Redox Biology · doi:10.1016/j.redox.2026.104231 · Cited by 3

Reduced aging defects in estrogen receptive brainstem nuclei in the female hamster

Gerrits, P. O., Kortekaas, R., Veening, J. G., de Weerd, H., & van der Want, J. J. L. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.02.018 · Cited by 2

Oxidation and Inflammation in the Immune and Nervous Systems, a Link Between Aging and Anxiety

la Fuente, M. D. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_115 · Cited by 3

Transport and Possible Outcome of Lipofuscin in Mouse Myocardium

Wang, L., Xiao, C.-Y., Li, J.-H., Tang, G.-C., & Xiao, S. (2022) · Advances in Gerontology · doi:10.1134/s207905702203016x · Cited by 2

Chronic neurotoxicity of Tetrabromobisphenol A: Induction of oxidative stress and damage to neurons in Caenorhabditis elegans

Yu, Y., Tan, S., Guo, H., Hua, X., Chen, H., Yang, Y., Xie, D., Yi, C., Ling, H., & Xiang, M. (2024) · Chemosphere · doi:10.1016/j.chemosphere.2024.141142 · Cited by 2

ε-Viniferin Rejuvenates Senescence via RGS16 Regulation: In Vitro Evidence

Park, J. H., Lee, K. S., Lee, K. S., Lee, Y. J., Yoon, J. H., So, B., Kim, D., Kim, M., Kwon, H. W., Byun, Y., et al. (2025) · Pharmaceuticals · doi:10.3390/ph18091254 · Cited by 2

Autophagy and Proteostasis in Cardiac Aging

Dai, D., & Rabinovitch, P. S. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-805253-2.00015-8 · Cited by 2

Chapter 15 Factors Underlying the Selective Vulnerability of Motor Neurons to Neurodegeneration

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Use it and lose it: lipofuscin accumulation in the midbrain of a coral reef fish

Gagliano, M., Lema, A. K., Depczynski, M., & Whalan, S. (2011) · Journal of Fish Biology · doi:10.1111/j.1095-8649.2010.02873.x · Cited by 2

Bilateral, geographic, peripapillary, chorioretinal atrophy in a patient with porphyria cutanea tarda and high iron stores

Denton, W. J., Jordan, C. W., & McGill, W. J. (2011) · Optometry · doi:10.1016/j.optm.2011.02.017 · Cited by 2

Spumiform capillary basement membrane swelling: a new type of microvascular degeneration in senescent hamster

Gerrits, P. O., Kortekaas, R., de Weerd, H., Veenstra-Algra, A., Luiten, P. G. M., van der Want, J. J. L., & Veening, J. G. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.09.009 · Cited by 2

Elucidation of Ageing on Low Dose Exposure to Neurotoxicant Dichlorvos in Invertebrate Model Caenorhabditis Elegans

Kisan, B. (2015) · MOJ Cell Science & Report · doi:10.15406/mojcsr.2015.02.00040 · Cited by 2

Biomarkers of Replicative Senescence Revisited

Nehlin, J. O. (2016) · Healthy ageing and longevity · doi:10.1007/978-3-319-26239-0_12 · Cited by 2

Can Lipofuscin Deposition on Renal Allograft Tubular Epithelium Be a Surrogate Marker for Kidney Allograft Aging?

Kawaguchi, Y., Oguchi, H., Mikami, T., Yamaguchi, Y., Ohashi, Y., Kawamura, T., Muramatsu, M., Itabashi, Y., Shinoda, K., Hyodo, Y., et al. (2019) · Transplantation Proceedings · doi:10.1016/j.transproceed.2019.03.017 · Cited by 2

Effects of temperature and salinity on the sub-Antarctic snail Xymenopsis muriciformis (King and Broderip, 1832): Medium-term exposure to different climate change scenarios

Ortíz, A., Arcos‐Ortega, G. F., & Navarro, J. M. (2021) · Journal of Experimental Marine Biology and Ecology · doi:10.1016/j.jembe.2021.151682 · Cited by 2

What is on the horizon for dry age-related macular degeneration drug treatment?

Rissotto, F., Sacconi, R., Apuzzo, A., Oldoni, G., Fusi, E., Servillo, A., Bandello, F. M., & Querques, G. (2023) · Expert Review of Ophthalmology · doi:10.1080/17469899.2023.2267179 · Cited by 2

Resources and habitat conditions of the bivalve mollusk Anadara broughtonii in the northern part of Amur Bay (Sea of Japan)

Седова, Л. Г., Витальевна, К. М., Sokolenko, D. A., & Иванович, Р. В. (2012) · Oceanology · doi:10.1134/s000143701204008x · Cited by 2

Microwave assisted synthesis for A2E and development of LC-ESI–MS method for quantification of ocular bisretinoids in human retina

Kotnala, A., Senthilkumari, S., Halder, N., Kumar, A., & Velpandian, T. (2017) · Journal of Chromatography B · doi:10.1016/j.jchromb.2017.11.021 · Cited by 2

Mouse Models for Friedreich's Ataxia

Puccio, H. M. (2006) · Elsevier eBooks · doi:10.1016/b978-012369462-1/50021-1 · Cited by 2

Human ageing, a biological view

Almeida, H., & Matos, L. (2015) · Wiley eBooks · doi:10.1002/9781118823408.ch1 · Cited by 2

Growing cells at 40% ambient oxygen conditions them to subsequent oxidative stress

Brunk, U. T. (2007) · Biogerontology · doi:10.1007/s10522-007-9091-9 · Cited by 2

Signaling Pathways that Regulate C. elegans Life Span

Ruvkun, G., Samuelson, A. V., Carr, C. E., Curran, S. P., & Shore, D. E. (2009) · Research and perspectives in endocrine interactions · doi:10.1007/978-3-642-04302-4_6 · Cited by 2

Aging of Florida Blue Crabs, Callinectes sapidus, Through the Biochemical Extraction of Lipofuscin

Crowley, C. E. (2012) · ProQuest Demo Repository · Cited by 2

Neuroanatomy and Neuropathology

Goettsche, K. R., Snow, C. E., & Avari, J. (2018) · Springer eBooks · doi:10.1007/978-3-319-73078-3_6 · Cited by 2

Observation of the Transport and Removal of Lipofuscin from the Mouse Myocardium using Transmission Electron MicroscopePreprint

Wang, L., Changyi, X., Jia-hua, L., Tang, G.-C., & Xiao, S. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.03.10.985507 · Cited by 2

TFEB/HLH-30-mediated expansion of neuronal lysosomal capacity in early adulthood protects dendrite maintenance during aging in Caenorhabditis elegansPreprint

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