Aging is defined as the progressive deterioration of physiological function with age. Incidence of many pathologies increases with age, including neurological and cardiovascular diseases and cancer. Aging tissues become less adaptable and renewable, and cells undergo senescence, a process by which they “irreversibly” stop dividing. Senescence has been shown to serve as a tumor suppression mechanism with clear desirable effects. However, senescence also has deleterious consequences, especially for cardiovascular, metabolic, and immune systems. Sphingolipids are a major class of lipids that regulate cell biology, owing to their structural and bioactive properties and diversity. Their involvement in the regulation of aging and senescence has been demonstrated and studied in multiple organisms and cell types, especially that of ceramide and sphingosine-1-phosphate; ceramide induces cellular senescence and sphingosine-1–phosphate delays it. These discoveries could be very useful in the future to understand aging mechanisms and improve therapeutic interventions.
Magali Trayssac, Yusuf A. Hannun, Lina M. Obeid
Title and authors | Publication | Year |
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Maturation and detoxification of synphilin-1 inclusion bodies regulated by sphingolipids
Cao X, Wu X, Zhao L, Zheng J, Jin X, Hao X, Winderickx J, Liu S, Chen L, Liu B |
eLife | 2025 |
Ceramides may Play a Central Role in the Pathogenesis of Alzheimer's Disease: a Review of Evidence and Horizons for Discovery.
Kalkman HO, Smigielski L |
Molecular neurobiology | 2025 |
Do circulating sphingolipid species correlate with age? A study in a normoglycemic biracial population.
Feto NA, Asuzu P, Wan J, Stentz F, Dagogo-Jack S, Mandal N |
Biogerontology | 2025 |
Bone and muscle crosstalk in ageing and disease.
Kirk B, Lombardi G, Duque G |
Nature reviews. Endocrinology | 2025 |
Regulatory Roles of Exosomes in Aging and Aging-Related Diseases.
Xiao N, Li Q, Liang G, Qian Z, Lin Y, Zhang H, Fu Y, Yang X, Zhang CT, Yang J, Liu A |
Biogerontology | 2025 |
Serum Proteomic and Metabolomic Signatures of High Versus Low Physical Function in Octogenarians.
Ubaida-Mohien C, Moaddel R, Spendiff S, MacMillan NJ, Filion ME, Morais JA, Candia J, Fitzgerald LF, Taivassalo T, Coen PM, Ferrucci L, Hepple RT |
Aging cell | 2025 |
GIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway.
Park AY, Leney-Greene M, Lynberg M, Gabrielski JQ, Xu X, Schwarz B, Zheng L, Balasubramaniyam A, Ham H, Chao B, Zhang Y, Matthews HF, Cui J, Yao Y, Kubo S, Chanchu JM, Morawski AR, Cook SA, Jiang P, Ravell JC, Cheng YH, George A, Faruqi A, Pagalilauan AM, Bergerson JRE, Ganesan S, Chauvin SD, Aluri J, Edwards-Hicks J, Bohrnsen E, Tippett C, Omar H, Xu L, Butcher GW, Pascall J, Karakoc-Aydiner E, Kiykim A, Maecker H, Tezcan İ, Esenboga S, Heredia RJ, Akata D, Tekin S, Kara A, Kuloglu Z, Unal E, Kendirli T, Dogu F, Karabiber E, Atkinson TP, Cochet C, Filhol O, Bosio CM, Davis MM, Lifton RP, Pearce EL, Daumke O, Aytekin C, Şahin GE, Aksu AÜ, Uzel G, Koneti Rao V, Sari S, Boztug K, Cagdas D, Haskologlu S, Ikinciogullari A, Schwefel D, Vilarinho S, Baris S, Ozen A, Su HC, Lenardo MJ |
Nature Immunology | 2024 |
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Jamjoum R, Majumder S, Issleny B, Stiban J |
Frontiers in physiology | 2024 |
Acid sphingomyelinase as a pathological and therapeutic target in neurological disorders: focus on Alzheimer's disease.
Choi BJ, Park MH, Jin HK, Bae JS |
Experimental & molecular medicine | 2024 |
Expression of Ceramide Synthases in Mice and Their Roles in Regulating Acyl-Chain Sphingolipids: A Framework for Baseline Levels and Future Implications in Aging and Disease
Richardson WJ, Humphrey SB, Sears SM, Hoffman NA, Orwick AJ, Doll MA, Doll CL, Xia C, Hernandez-Corbacho M, Snider JM, Obeid LM, Hannun YA, Snider AJ, Siskind LJ |
Molecular pharmacology | 2024 |
LPD-3 as a megaprotein brake for aging and insulin-mTOR signaling in C. elegans
Pandey T, Wang B, Wang C, Zu J, Deng H, Shen K, do Vale GD, McDonald JG, Ma DK |
Cell Reports | 2024 |
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Moseholm KF, Horn JW, Fitzpatrick AL, Djoussé L, Longstreth WT Jr, Lopez OL, Hoofnagle AN, Jensen MK, Lemaitre RN, Mukamal KJ |
Frontiers in neurology | 2024 |
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Experimental Neurology | 2024 |
Hepatic-Metabolic Activity of α-Lipoic Acid—Its Influence on Sphingolipid Metabolism and PI3K/Akt/mTOR Pathway in a Rat Model of Metabolic Dysfunction-Associated Steatotic Liver Disease
Sztolsztener K, Chabowski A |
Nutrients | 2024 |
N-Acetylcysteine Alleviates Impaired Muscular Function Resulting from Sphingosine Phosphate Lyase Functional Deficiency-Induced Sphingoid Base and Ceramide Accumulation in Caenorhabditis elegans
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Nutrients | 2024 |
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Fretts AM, Jensen PN, Sitlani CM, Hoofnagle A, Lidgard B, Umans JG, Siscovick DS, King IB, Howard BV, Cole SA, Lemaitre RN |
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease | 2024 |
Tafazzin deficiency causes substantial remodeling in the lipidome of a mouse model of Barth Syndrome cardiomyopathy.
Hachmann M, Gülcan G, Rajendran R, Höring M, Liebisch G, Bachhuka A, Kohlhaas M, Maack C, Ergün S, Dudek J, Karnati S |
2024 | |
Emerging role of sphingolipids and extracellular vesicles in development and therapeutics of cardiovascular diseases.
Bhat OM, Mir RA, Nehvi IB, Wani NA, Dar AH, Zargar MA |
International journal of cardiology. Heart & vasculature | 2024 |
Long-term effects of siponimod on cardiovascular and autonomic nervous system in secondary progressive multiple sclerosis.
Constantinescu V, Haase R, Akgün K, Ziemssen T |
Frontiers in pharmacology | 2024 |
Cell senescence in cardiometabolic diseases
Grootaert MO |
NPJ Aging | 2024 |
A Single-Cell Metabolic Profiling Characterizes Human Aging via SlipChip-SERS.
Liu F, Liu J, Luo Y, Wu S, Liu X, Chen H, Luo Z, Yuan H, Shen F, Zhu F, Ye J |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) | 2024 |
Time-restricted eating reveals a “younger” immune system and reshapes the intestinal microbiome in human
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Redox Biology | 2024 |
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Wang S, Jin Z, Wu B, Morris AJ, Deng P |
Journal of Lipid Research | 2024 |
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ASN NEURO | 2024 |
Phenotypic upregulation of hexocylceramides and ether‐linked phosphocholines as markers of human extreme longevity
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Aging Cell | 2024 |
The role of ApoE-mediated microglial lipid metabolism in brain aging and disease
Yen JH, Yu IC |
2023 | |
Insulin-mTOR hyperfunction drives C. elegans aging opposed by the megaprotein LPD-3
Pandey T, Wang B, Zu J, Deng H, Shen K, do Vale GD, McDonald JG, Ma DK |
2023 | |
Untargeted analysis in post-COVID-19 patients reveals dysregulated lipid pathways two years after recovery
López-Hernández Y, Oropeza-Valdez JJ, García Lopez DA, Borrego JC, Murgu M, Valdez J, López JA, Monárrez-Espino J |
Frontiers in Molecular Biosciences | 2023 |
Functional roles of sphingolipids in immunity and their implication in disease.
Lee M, Lee SY, Bae YS |
Experimental & molecular medicine | 2023 |
Ceramide in cerebrovascular diseases.
Yuan H, Zhu B, Li C, Zhao Z |
Frontiers in cellular neuroscience | 2023 |
Evaluation of plasma sphingolipids as mediators of the relationship between kidney disease and cardiovascular events.
Lidgard B, Bansal N, Zelnick LR, Hoofnagle AN, Fretts AM, Longstreth WT Jr, Shlipak MG, Siscovick DS, Umans JG, Lemaitre RN |
EBioMedicine | 2023 |
Glycolipids in Parkinson's disease: beyond neuronal function.
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FEBS Open Bio | 2023 |
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Liu B, Meng Q, Gao X, Sun H, Xu Z, Wang Y, Zhou H |
Frontiers in Nutrition | 2023 |
High-Density Lipoprotein Lipidomics and Mortality in CKD
Lidgard B, Hoofnagle AN, Zelnick LR, de Boer IH, Fretts AM, Kestenbaum BR, Lemaitre RN, Robinson-Cohen C, Bansal N |
2023 | |
Integrative metabolome and lipidome analyses of plasma in neovascular macular degeneration
Zhao T, Li J, Wang Y, Guo X, Sun Y |
Heliyon | 2023 |
Lipidomic Alterations in the Cerebral Cortex and White Matter in Sporadic Alzheimer’s Disease
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Aging and disease | 2023 |
Skewing cPLA2 activity toward oxoeicosanoid production promotes neutrophil N2 polarization, wound healing, and the response to sepsis
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Science signaling | 2023 |
TMT-Based Proteomics Analysis Revealed the Protein Changes in Perirenal Fat from Obese Rabbits
Jiang G, Shao J, Tang T, Wang M, Wang J, Jia X, Lai S |
International journal of molecular sciences | 2023 |
Cross-sectional analysis of healthy individuals across decades: Aging signatures across multiple physiological compartments.
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Aging Cell | 2023 |
Prognostic significance of senescence-related tumor microenvironment genes in head and neck squamous cell carcinoma
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Aging | 2023 |
A Comparison of Bone Microarchitectural and Transcriptomic Changes in Murine Long Bones in Response to Hindlimb Unloading and Aging
Meas SJ, Daire GM, Friedman MA, DeNapoli R, Ghosh P, Farr JN, Donahue HJ |
Bone | 2023 |
The Potential Antipyretic Mechanism of Ellagic Acid with Brain Metabolomics Using Rats with Yeast-Induced Fever
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Molecules (Basel, Switzerland) | 2022 |
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Molecular Psychiatry | 2022 |
Eryptosis: Programmed Death of Nucleus-Free, Iron-Filled Blood Cells
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Cells | 2022 |
Toxic Mechanism and Biological Detoxification of Fumonisins
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Toxins | 2022 |
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Bioactive Materials | 2022 |
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Metabolites | 2022 |
Skeletal Muscle and COVID-19: The Potential Involvement of Bioactive Sphingolipids
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Biomedicines | 2022 |
Implications of Sphingolipids on Aging and Age-Related Diseases
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2022 | |
Metabolomic Profile of Different Dietary Patterns and Their Association with Frailty Index in Community-Dwelling Older Men and Women
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Nutrients | 2022 |
Lipidomics profiling of biological aging in American Indians: the Strong Heart Family Study.
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GeroScience | 2022 |
Aryl hydrocarbon receptor (AhR) reveals evidence of antagonistic pleiotropy in the regulation of the aging process
Salminen A |
Cellular and Molecular Life Sciences | 2022 |
Diverse Roles of Ceramide in the Progression and Pathogenesis of Alzheimer’s Disease
Chowdhury MR, Jin HK, Bae JS |
Biomedicines | 2022 |
Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies
Raza Y, Atallah J, Luberto C |
International journal of molecular sciences | 2022 |
Extracellular Vesicles as Communicators of Senescence in Musculoskeletal Aging
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JBMR Plus | 2022 |
S1P receptor modulators and the cardiovascular autonomic nervous system in multiple sclerosis: a narrative review
Constantinescu V, Haase R, Akgün K, Ziemssen T |
Therapeutic advances in neurological disorders | 2022 |
Communications between Mitochondria and Endoplasmic Reticulum in the Regulation of Metabolic Homeostasis
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Cells | 2021 |
Alterations in β-Cell Sphingolipid Profile Associated with ER Stress and iPLA2β: Another Contributor to β-Cell Apoptosis in Type 1 Diabetes
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Molecules (Basel, Switzerland) | 2021 |
Sphingolipids as a Culprit of Mitochondrial Dysfunction in Insulin Resistance and Type 2 Diabetes
K Roszczyc-Owsiejczuk, P Zabielski |
Frontiers in Endocrinology | 2021 |
Bioactive sphingolipids: Advancements and contributions from the laboratory of Dr. Lina M. Obeid
FN Velazquez, M Hernandez-Corbacho, M Trayssac, JL Stith, J Bonica, B Jean, MJ Pulkoski-Gross, BL Carroll, MF Salama, YA Hannun, AJ Snider |
Cellular Signalling | 2021 |
The metabolic roots of senescence: mechanisms and opportunities for intervention
CD Wiley, J Campisi |
2021 | |
Role of Choline in Ocular Diseases
JS Hwang, YJ Shin |
International journal of molecular sciences | 2021 |
Aging-dependent mitochondrial dysfunction mediated by ceramide signaling inhibits antitumor T cell response
S Vaena, P Chakraborty, HG Lee, AH Janneh, MF Kassir, G Beeson, Z Hedley, A Yalcinkaya, MH Sofi, H Li, ML Husby, RV Stahelin, XZ Yu, S Mehrotra, B Ogretmen |
Cell Reports | 2021 |
Metabolomics and cardiovascular imaging: a combined approach for cardiovascular ageing
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ESC Heart Failure | 2021 |
Circulating Ceramides and Sphingomyelins and Risk of Mortality: The Cardiovascular Health Study
AM Fretts, PN Jensen, AN Hoofnagle, B McKnight, CM Sitlani, DS Siscovick, IB King, BM Psaty, N Sotoodehnia, RN Lemaitre |
Clinical chemistry | 2021 |
Neutral sphingomyelinase‐2 and cardiometabolic diseases
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Obesity reviews : an official journal of the International Association for the Study of Obesity | 2021 |
Targeting sphingosine kinase 1 (SK1) enhances oncogene-induced senescence through ceramide synthase 2 (CerS2)-mediated generation of very-long-chain ceramides
M Trayssac, CJ Clarke, JL Stith, JM Snider, N Newen, CR Gault, YA Hannun, LM Obeid |
Cell Death and Disease | 2021 |
Faecal miRNA profiles associated with age, sex, BMI, and lifestyle habits in healthy individuals
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Scientific Reports | 2021 |
Metabolic View on Human Healthspan: A Lipidome-Wide Association Study
J Carrard, H Gallart-Ayala, D Infanger, T Teav, J Wagner, R Knaier, F Colledge, L Streese, K Königstein, T Hinrichs, H Hanssen, J Ivanisevic, A Schmidt-Trucksäss |
Metabolites | 2021 |
Lipid alterations in human frontal cortex in ALS‐FTLD‐TDP43 proteinopathy spectrum are partly related to peroxisome impairment
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Neuropathology and Applied Neurobiology | 2021 |
Long-Term Administration of Triterpenoids From Ganoderma lucidum Mitigates Age-Associated Brain Physiological Decline via Regulating Sphingolipid Metabolism and Enhancing Autophagy in Mice
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Frontiers in aging neuroscience | 2021 |
The Functional Role of Sphingosine Kinase 2
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Frontiers in Molecular Biosciences | 2021 |
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Scientific Reports | 2021 |
Convergence: Lactosylceramide-Centric Signaling Pathways Induce Inflammation, Oxidative Stress, and Other Phenotypic Outcomes
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International journal of molecular sciences | 2021 |
Impact of sphingosine and acetylsphingosines on the aggregation and toxicity of metal-free and metal-treated amyloid-β
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Chemical Science | 2021 |
Sphingolipidomics in Translational Sepsis Research–Biomedical Considerations and Perspectives
RA Claus, MH Graeler |
Frontiers in Medicine | 2021 |
Human iPSC-based neurodevelopmental models of globoid cell leukodystrophy uncover patient- and cell type-specific disease phenotypes
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Stem Cell Reports | 2021 |
Age-Related Changes in Lipidome of Rat Frontal Cortex and Cerebellum Are Partially Reversed by Methionine Restriction Applied in Old Age
M Jové, R Cabré, N Mota-Martorell, M Martin-Garí, È Obis, P Ramos, I Canales, JD Galo-Licona, J Sol, L Nogueras, P Torres, M Portero-Otín, V Ayala, I Ferrer, R Pamplona |
International journal of molecular sciences | 2021 |
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Cardiovascular Diabetology | 2021 |
Long-lived Humans Have a Unique Plasma Sphingolipidome
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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences | 2021 |
Pro-Senescence and Anti-Senescence Mechanisms of Cardiovascular Aging: Cardiac MicroRNA Regulation of Longevity Drug-Induced Autophagy
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Frontiers in pharmacology | 2020 |
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2020 | |
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Journal of Internal Medicine | 2020 |
In Vivo Anti-Inflammatory Effects and Related Mechanisms of Processed Egg Yolk, a Potential Anti-Inflammaging Dietary Supplement
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Journal of Endocrinological Investigation | 2020 |
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Biomolecules | 2020 |
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Progress in Lipid Research | 2020 |
Potential Role of Phosphoglycerol Dihydroceramide Produced by Periodontal Pathogen Porphyromonas gingivalis in the Pathogenesis of Alzheimer’s Disease
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Frontiers in immunology | 2020 |
Skin Recovery After Discontinuation of Long-Term Moisturizer Application: A Split-Face Comparison Pilot Study
JT Maul, LV Maul, M Kägi, P Cheng, F Anzengruber, M von Laue, Y Chen, M Kägi, A Navarini |
Dermatology and Therapy | 2020 |
Ceramides Profile Identifies Patients with More Advanced Stages of Colorectal Cancer
AR Markowski, AU Błachnio-Zabielska, K Guzińska-Ustymowicz, A Markowska, K Pogodzińska, K Roszczyc, J Zińczuk, P Zabielski |
Biomolecules | 2020 |
The Lipidome Fingerprint of Longevity
M Jové, N Mota-Martorell, I Pradas, JD Galo-Licona, M Martín-Gari, È Obis, J Sol, R Pamplona |
Molecules (Basel, Switzerland) | 2020 |
Sphingolipids as Emerging Mediators in Retina Degeneration
MV Simón, FH Spalm, MS Vera, NP Rotstein |
Frontiers in cellular neuroscience | 2019 |
Incomplete Healing as a Cause of Aging: The Role of Mitochondria and the Cell Danger Response
RK Naviaux |
Biology : open access journal | 2019 |
Sphk2−/− mice are protected from obesity and insulin resistance
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Ceramide and Regulation of Vascular Tone
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International journal of molecular sciences | 2019 |
Advances in determining signaling mechanisms of ceramide and role in disease
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Journal of lipid research | 2019 |
Sphingolipid/Ceramide Pathways and Autophagy in the Onset and Progression of Melanoma: Novel Therapeutic Targets and Opportunities
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International journal of molecular sciences | 2019 |
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BMB Reports | 2019 |
Sarcosine Is Uniquely Modulated by Aging and Dietary Restriction in Rodents and Humans
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