Targeting cellular senescence with senotherapeutics: senolytics and senomorphics

Senolytic combination of Dasatinib and Quercetin alleviates intestinal senescence and inflammation and modulates the gut microbiome in aged mice

(2021) Tatiana Dandolini Saccon et al.   JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES

Roxithromycin attenuates bleomycin-induced pulmonary fibrosis by targeting senescent cells

(2021) Xuan Zhang et al.   ACTA PHARMACOLOGICA SINICA

Identification of GL-V9 as a novel senolytic agent against senescent breast cancer cells

(2021) Dawei Yang et al.   LIFE SCIENCES

Novel small molecule inhibition of IKK/NF‐κB activation reduces markers of senescence and improves healthspan in mouse models of aging

(2021) Lei Zhang et al.   AGING CELL

FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice

(2020) Chi Zhang et al.   Aging-US

Proteolysis-Targeting Chimeras as Therapeutics and Tools for Biological Discovery

(2020) George M. Burslem et al.   CELL

Discovery, Development, and Future Application of Senolytics: Theories and Predictions

(2020) Erin O. Wissler Gerdes et al.   FEBS Journal

mTOR at the nexus of nutrition, growth, ageing and disease

(2020) Grace Y. Liu et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Metformin Reduces the Senescence of Renal Tubular Epithelial Cells in Diabetic Nephropathy via the MBNL1/miR-130a-3p/STAT3 Pathway

(2020) Xue Jiang et al.   Oxidative Medicine and Cellular Longevity

The JAK1/2 inhibitor ruxolitinib delays premature aging phenotypes

(2020) Audrey Griveau et al.   AGING CELL

Galacto‐conjugation of Navitoclax as an efficient strategy to increase senolytic specificity and reduce platelet toxicity

(2020) Estela González‐Gualda et al.   AGING CELL

Galactose‐modified duocarmycin prodrugs as senolytics

(2020) Ana Guerrero et al.   AGING CELL

ATM is a key driver of NF-κB-dependent DNA-damage-induced senescence, stem cell dysfunction and aging

(2020) Jing Zhao et al.   Aging-US

Identification of SYK inhibitor, R406 as a novel senolytic agent

(2020) Hyun-Ji Cho et al.   Aging-US

Resveratrol inhibits adipocyte differentiation and cellular senescence of human bone marrow stromal stem cells

(2020) Dalia Ali et al.   BONE

Benefits of Metformin in Attenuating the Hallmarks of Aging

(2020) Ameya S. Kulkarni et al.   Cell Metabolism

Elimination of senescent cells by β-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice

(2020) Yusheng Cai et al.   CELL RESEARCH

Potential Adverse Effects of Resveratrol: A Literature Review

(2020) Abdullah Shaito et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

JAK2/STAT3 regulates estrogen-related senescence of bone marrow stem cells

(2020) Wenjing Wu et al.   JOURNAL OF ENDOCRINOLOGY

SIRT1 and aging related signaling pathways

(2020) Cui Chen et al.   MECHANISMS OF AGEING AND DEVELOPMENT

A BET family protein degrader provokes senolysis by targeting NHEJ and autophagy in senescent cells

(2020) Masahiro Wakita et al.   Nature Communications

Role of p53 in the Regulation of Cellular Senescence

(2020) Mahmut Mijit et al.   Biomolecules

Senolytic drugs: from discovery to translation

(2020) J. L. Kirkland et al.   JOURNAL OF INTERNAL MEDICINE

The senescence-associated secretome as an indicator of age and medical risk

(2020) Marissa J. Schafer et al.   JCI Insight

Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span

(2020) Paul D. Robbins et al.   Annual Review of Pharmacology and Toxicology

Senotherapeutic drugs for human intervertebral disc degeneration and low back pain

(2020) Hosni Cherif et al.   eLife

The Target of Rapamycin Signalling Pathway in Ageing and Lifespan Regulation

(2020) Ivana Bjedov et al.   Genes

Effect of rapamycin on aging and age-related diseases—past and future

(2020) Ramasamy Selvarani et al.   GeroScience

Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study

(2019) Jamie N. Justice et al.   EBioMedicine

NAD+ metabolism governs the proinflammatory senescence-associated secretome

(2019) Timothy Nacarelli et al.   NATURE CELL BIOLOGY

The curcumin analog EF24 is a novel senolytic agent

(2019) Wen Li et al.   Aging-US

Senolytic therapy alleviates Aβ-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer’s disease model

(2019) Peisu Zhang et al.   NATURE NEUROSCIENCE

Curcumin and o-Vanillin Exhibit Evidence of Senolytic Activity in Human IVD Cells In Vitro

(2019) Hosni Cherif et al.   Journal of Clinical Medicine

Senescent cells evade immune clearance via HLA-E-mediated NK and CD8+ T cell inhibition

(2019) Branca I. Pereira et al.   Nature Communications

A novel rapamycin analog is highly selective for mTORC1 in vivo

(2019) Katherine H. Schreiber et al.   Nature Communications

Fibrates as drugs with senolytic and autophagic activity for osteoarthritis therapy

(2019) Uxía Nogueira-Recalde et al.   EBioMedicine

Cellular senescence: at the nexus between ageing and diabetes

(2019) Allyson K. Palmer et al.   DIABETOLOGIA

Inhibiting protein-protein interactions of Hsp90 as a novel approach for targeting cancer

(2019) Sayan Dutta Gupta et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Mitotic catastrophe and p53-dependent senescence induction in T-cell malignancies exposed to nonlethal dosage of GL-V9

(2019) Hui Li et al.   ARCHIVES OF TOXICOLOGY

Directed elimination of senescent cells attenuates development of osteoarthritis by inhibition of c-IAP and XIAP

(2019) Wang Peilin et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

Flavonoid GL-V9 induces apoptosis and inhibits glycolysis of breast cancer via disrupting GSK-3β-modulated mitochondrial binding of HKII

(2019) Yongjian Guo et al.   FREE RADICAL BIOLOGY AND MEDICINE

Identification and characterization of Cardiac Glycosides as senolytic compounds

(2019) Francisco Triana-Martínez et al.   Nature Communications

Aspirin and its pleiotropic application

(2019) Jolanta Hybiak et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

Metformin alleviates human cellular aging by upregulating the endoplasmic reticulum glutathione peroxidase 7

(2018) Jingqi Fang et al.   AGING CELL

Oxidation resistance 1 is a novel senolytic target

(2018) Xin Zhang et al.   AGING CELL

A review on the chemotherapeutic potential of fisetin: In vitro evidences

(2018) Kiruthika Sundarraj et al.   BIOMEDICINE & PHARMACOTHERAPY

Senolytic activity of piperlongumine analogues: Synthesis and biological evaluation

(2018) Xingui Liu et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Selective elimination of senescent cells by mitochondrial targeting is regulated by ANT2

(2018) Sona Hubackova et al.   CELL DEATH AND DIFFERENTIATION

A versatile drug delivery system targeting senescent cells

(2018) Daniel Muñoz‐Espín et al.   EMBO Molecular Medicine

Regulation of cellular senescence via the FOXO4-p53 axis

(2018) Benjamin Bourgeois et al.   FEBS LETTERS

Senolytics improve physical function and increase lifespan in old age

(2018) Ming Xu et al.   NATURE MEDICINE

Senotherapeutics for healthy ageing

(2018) Laura J. Niedernhofer et al.   NATURE REVIEWS DRUG DISCOVERY

Development of novel NEMO-binding domain mimetics for inhibiting IKK/NF-κB activation

(2018) Jing Zhao et al.   PLOS BIOLOGY

Tau protein aggregation is associated with cellular senescence in the brain

(2018) Nicolas Musi et al.   AGING CELL

Fisetin is a senotherapeutic that extends health and lifespan

(2018) Matthew J. Yousefzadeh et al.   EBioMedicine

Azithromycin and Roxithromycin define a new family of “senolytic” drugs that target senescent human fibroblasts

(2018) Bela Ozsvari et al.   Aging-US

Impaired immune surveillance accelerates accumulation of senescent cells and aging

(2018) Yossi Ovadya et al.   Nature Communications

mTOR as Regulator of Lifespan, Aging, and Cellular Senescence: A Mini-Review

(2017) Thomas Weichhart   GERONTOLOGY

Targeting senescent cholangiocytes and activated fibroblasts with B-cell lymphoma-extra large inhibitors ameliorates fibrosis in multidrug resistance 2 gene knockout (Mdr2−/− ) mice

(2017) Anja Moncsek et al.   HEPATOLOGY

Modulation of the Senescence-Associated Inflammatory Phenotype in Human Fibroblasts by Olive Phenols

(2017) Beatrice Menicacci et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Antioxidant and Anti-Senescence Effect of Metformin on Mouse Olfactory Ensheathing Cells (mOECs) May Be Associated with Increased Brain-Derived Neurotrophic Factor Levels—An Ex Vivo Study

(2017) Agnieszka Śmieszek et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Chemical screening identifies ATM as a target for alleviating senescence

(2017) Hyun Tae Kang et al.   Nature Chemical Biology

Targeting cellular senescence prevents age-related bone loss in mice

(2017) Joshua N Farr et al.   NATURE MEDICINE

Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment

(2017) Ok Hee Jeon et al.   NATURE MEDICINE

Cellular senescence mediates fibrotic pulmonary disease

(2017) Marissa J. Schafer et al.   Nature Communications

Identification of HSP90 inhibitors as a novel class of senolytics

(2017) Heike Fuhrmann-Stroissnigg et al.   Nature Communications

Cellular senescence drives age-dependent hepatic steatosis

(2017) Mikolaj Ogrodnik et al.   Nature Communications

A Novel Indication for Panobinostat as a Senolytic Drug in NSCLC and HNSCC

(2017) Leleesha Samaraweera et al.   Scientific Reports

Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice

(2016) Carolyn M. Roos et al.   AGING CELL

Metformin-mediated increase in DICER1 regulates microRNA expression and cellular senescence

(2016) Nicole Noren Hooten et al.   AGING CELL

Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors

(2016) Yi Zhu et al.   AGING CELL

Discovery of piperlongumine as a potential novel lead for the development of senolytic agents

(2016) Yingying Wang et al.   Aging-US

Multiple facets of p53 in senescence induction and maintenance

(2016) Yoshikazu Johmura et al.   CANCER SCIENCE

Metformin as a Tool to Target Aging

(2016) Nir Barzilai et al.   Cell Metabolism

Resveratrol and Lifespan in Model Organisms

(2016) Kathrin Pallauf et al.   CURRENT MEDICINAL CHEMISTRY

Targeting Senescent Cells: Possible Implications for Delaying Skin Aging: A Mini-Review

(2016) Michael C. Velarde et al.   GERONTOLOGY

Transplanted Senescent Cells Induce an Osteoarthritis-Like Condition in Mice

(2016) Ming Xu et al.   JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES

Induced protein degradation: an emerging drug discovery paradigm

(2016) Ashton C. Lai et al.   NATURE REVIEWS DRUG DISCOVERY

Exploring the molecular targets of dietary flavonoid fisetin in cancer

(2016) Deeba N. Syed et al.   SEMINARS IN CANCER BIOLOGY

Genistein-induced LKB1–AMPK activation inhibits senescence of VSMC through autophagy induction

(2016) Kyung Young Lee et al.   VASCULAR PHARMACOLOGY

Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL

(2016) Reut Yosef et al.   Nature Communications

Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse

(2016) Marco Demaria et al.   Cancer Discovery

If started early in life, metformin treatment increases life span and postpones tumors in female SHR mice

(2016) Vladimir N. Anisimov et al.   Aging-US

Impacts of metformin and aspirin on life history features and longevity of crickets: trade-offs versus cost-free life extension?

(2015) Harvir Hans et al.   AGE

The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs

(2015) Yi Zhu et al.   AGING CELL

Monitoring Lipid Peroxidation within Foam Cells by Lysosome-Targetable and Ratiometric Probe

(2015) Xinfu Zhang et al.   ANALYTICAL CHEMISTRY

Effects of flavonoids on senescence-associated secretory phenotype formation from bleomycin-induced senescence in BJ fibroblasts

(2015) Hyun Lim et al.   BIOCHEMICAL PHARMACOLOGY

Lifespan and healthspan extension by resveratrol

(2015) Khushwant S. Bhullar et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

The molecular targets of resveratrol

(2015) Sameer S. Kulkarni et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

Suppression of the senescence-associated secretory phenotype (SASP) in human fibroblasts using small molecule inhibitors of p38 MAP kinase and MK2

(2015) Dauren Alimbetov et al.   BIOGERONTOLOGY

Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4

(2015) Jing Lu et al.   CHEMISTRY & BIOLOGY

Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity

(2015) Allyson K. Palmer et al.   DIABETES

MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation

(2015) Remi-Martin Laberge et al.   NATURE CELL BIOLOGY

Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice

(2015) Jianhui Chang et al.   NATURE MEDICINE

JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age

(2015) Ming Xu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy

(2015) Joel D. Leverson et al.   Science Translational Medicine

Simvastatin suppresses breast cancer cell proliferation induced by senescent cells

(2015) Su Liu et al.   Scientific Reports

Geroscience: Linking Aging to Chronic Disease

(2014) Brian K. Kennedy et al.   CELL

Metformin: From Mechanisms of Action to Therapies

(2014) Marc Foretz et al.   Cell Metabolism

Rapamycin: One Drug, Many Effects

(2014) Jing Li et al.   Cell Metabolism

Cellular senescence and the senescent secretory phenotype in age-related chronic diseases

(2014) Yi Zhu et al.   CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE

An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA

(2014) Marco Demaria et al.   DEVELOPMENTAL CELL

Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls

(2014) C. A. Bannister et al.   DIABETES OBESITY & METABOLISM

Small molecule SIRT1 activators for the treatment of aging and age-related diseases

(2014) Basil P. Hubbard et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

The SIRT1 Activator SRT1720 Extends Lifespan and Improves Health of Mice Fed a Standard Diet

(2014) Sarah J. Mitchell et al.   Cell Reports

Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males

(2013) David E. Harrison et al.   AGING CELL

Metformin inhibits the senescence-associated secretory phenotype by interfering with IKK/NF-κB activation

(2013) Olga Moiseeva et al.   AGING CELL

The Hallmarks of Aging

(2013) Carlos López-Otín et al.   CELL

Programmed Cell Senescence during Mammalian Embryonic Development

(2013) Daniel Muñoz-Espín et al.   CELL

Metformin Retards Aging in C. elegans by Altering Microbial Folate and Methionine Metabolism

(2013) Filipe Cabreiro et al.   CELL

Rapalogs and mTOR inhibitors as anti-aging therapeutics

(2013) Dudley W. Lamming et al.   JOURNAL OF CLINICAL INVESTIGATION

Senescence and aging: the critical roles of p53

(2013) A Rufini et al.   ONCOGENE

Metformin improves healthspan and lifespan in mice

(2013) Alejandro Martin-Montalvo et al.   Nature Communications

Fisetin: A Dietary Antioxidant for Health Promotion

(2012) Naghma Khan et al.   ANTIOXIDANTS & REDOX SIGNALING

Cellular senescence and cancer chemotherapy resistance

(2012) Ryan R. Gordon et al.   DRUG RESISTANCE UPDATES

Nuclear lamina defects cause ATM-dependent NF- B activation and link accelerated aging to a systemic inflammatory response

(2012) F. G. Osorio et al.   GENES & DEVELOPMENT

NF-κB inhibition delays DNA damage–induced senescence and aging in mice

(2012) Jeremy S. Tilstra et al.   JOURNAL OF CLINICAL INVESTIGATION

Chronic Resveratrol Treatment Ameliorates Cell Adhesion and Mitigates the Inflammatory Phenotype in Senescent Human Fibroblasts

(2012) V. Pitozzi et al.   JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES

Age-Associated Proinflammatory Secretory Phenotype in Vascular Smooth Muscle Cells From the Non-human Primate Macaca mulatta: Reversal by Resveratrol Treatment

(2012) A. Csiszar et al.   JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES

Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study

(2012) Karen Barnett et al.   LANCET

Aging with multimorbidity: A systematic review of the literature

(2011) Alessandra Marengoni et al.   AGEING RESEARCH REVIEWS

Bcl-xL-inhibitory BH3 mimetics can induce a transient thrombocytopathy that undermines the hemostatic function of platelets

(2011) S. M. Schoenwaelder et al.   BLOOD

Metformin slows down aging and extends life span of female SHR mice

(2011) Vladimir N. Anisimov et al.   CELL CYCLE

Emerging role of NF-κB signaling in the induction of senescence-associated secretory phenotype (SASP)

(2011) Antero Salminen et al.   CELLULAR SIGNALLING

p38MAPK is a novel DNA damage response-independent regulator of the senescence-associated secretory phenotype

(2011) Adam Freund et al.   EMBO JOURNAL

Inhibitory effects of GL-V9 on the invasion of human breast carcinoma cells by downregulating the expression and activity of matrix metalloproteinase-2/9

(2011) Liwen Li et al.   EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

GL-V9, a newly synthetic flavonoid derivative, induces mitochondrial-mediated apoptosis and G2/M cell cycle arrest in human hepatocellular carcinoma HepG2 cells

(2011) Liwen Li et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

Inhibition of p38 MAPK Attenuates Ionizing Radiation-Induced Hematopoietic Cell Senescence and Residual Bone Marrow Injury

(2011) Yong Wang et al.   RADIATION RESEARCH

SRT1720 improves survival and healthspan of obese mice

(2011) Robin K. Minor et al.   Scientific Reports

The Senescence-Associated Secretory Phenotype: The Dark Side of Tumor Suppression

(2010) Jean-Philippe Coppé et al.   Annual Review of Pathology-Mechanisms of Disease

Induction of Endothelial Nitric Oxide Synthase, SIRT1, and Catalase by Statins Inhibits Endothelial Senescence Through the Akt Pathway

(2010) Hidetaka Ota et al.   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

Anti-ageing and rejuvenating effects of quercetin

(2010) Niki Chondrogianni et al.   EXPERIMENTAL GERONTOLOGY

HSP90 at the hub of protein homeostasis: emerging mechanistic insights

(2010) Mikko Taipale et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Metformin Induces a Dietary Restriction–Like State and the Oxidative Stress Response to Extend C. elegans Healthspan via AMPK, LKB1, and SKN-1

(2010) Brian Onken et al.   PLoS One

SIRT6 Links Histone H3 Lysine 9 Deacetylation to NF-κB-Dependent Gene Expression and Organismal Life Span

(2009) Tiara L.A. Kawahara et al.   CELL

Selective p38α Inhibitors Clinically Evaluated for the Treatment of Chronic Inflammatory Disorders

(2009) David M. Goldstein et al.   JOURNAL OF MEDICINAL CHEMISTRY

Rapamycin fed late in life extends lifespan in genetically heterogeneous mice

(2009) David E. Harrison et al.   NATURE

Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion

(2009) Francis Rodier et al.   NATURE CELL BIOLOGY

Resveratrol reduces endothelial progenitor cells senescence through augmentation of telomerase activity by Akt-dependent mechanisms

(2008) L Xia et al.   BRITISH JOURNAL OF PHARMACOLOGY

ABT-263: A Potent and Orally Bioavailable Bcl-2 Family Inhibitor

(2008) C. Tse et al.   CANCER RESEARCH

Oncogenic BRAF Induces Senescence and Apoptosis through Pathways Mediated by the Secreted Protein IGFBP7

(2008) Narendra Wajapeyee et al.   CELL

Chemokine Signaling via the CXCR2 Receptor Reinforces Senescence

(2008) Juan C. Acosta et al.   CELL

Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor

(2008) Jean-Philippe Coppé et al.   PLOS BIOLOGY