Buck Institute for Research on Aging

Unity Biotechnology, Inc.

Mayo Foundation for Medical Education and Research

University of California

Johns Hopkins University

Erasmus University Medical Center Rotterdam

California Pacific Medical Center Research Institute

Geron Corporation

Kythera Biopharmaceuticals, Inc.

California Pacific Medical Center

Universitat Fur Bodenkultur Wien

Buck Institute for Research Aging

Judith Campisi

Remi-Martin Laberge

Marco Demaria

Nathaniel E David

James L Kirkland

Tamar Tchkonia

Yi Zhu

Jan M A Van Deursen

Alain Philippe Vasserot

Darren J Baker

Bennett G Childs

Albert Davalos

Jennifer H Elisseeff

Pierre-Yves Desprez

Okhee Jeon

Francis Rodier

Chaekyu Kim

James Mitchell

Jan H J Hoeijmakers

Wendy Toussaint

Monica Peacocke

Serge P Lichtsteiner

Johannes Grillari

Matthias Hackl

Sahn-Ho Kim

Goberdhan P Dirmi

Goberdhan P Dimri

Alessandro Testori

Abhijit Kale

Jan Ma Van Deursen

Nathaniel David

Jennifer Elisseeff

Jan MA Van Deursen

Jan M Van Deursen

This invention establishes a new paradigm for treatment of Parkinson's disease (PD) by eliminating senescent cells that reside in or around the site of the disease pathophysiology. Exposure of test subjects to the herbicide paraquat (PQ) increases the risk for developing Parkinson's disease. The data in this disclosure show that PQ induces a senescence arrest and SASP in astrocytes, in culture and in vivo in mice, and senescent cell markers were present in astrocytes in midbrain tissue from PD patients. In a transgenic mouse model, senescent cell ablation protected against PQ-induced PD-like neuropathology. Removal of senescent cells from affected sites using small molecule agents that specifically target senescent cells can help prevent or ameliorate signs and symptoms of the disease.

Treatment of a senescence-associated ocular disease or disorder using a Bcl-xL selective inhibitor

Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.

Treating liver disease by selectively eliminating senescent cells

Treating cardiovascular disease by selectively eliminating senescent cells

The present invention provides a method of detecting senescent cells or diagnosing cellular senescence in a subject wherein the level of one or more selected miRNAs is quantified in a sample from said subject.

Biomarkers for detecting senescent cells

Treating cognitive decline and other neurodegenerative conditions by selectively removing senescent cells from neurological tissue

This disclosure provides non-human animal models for age-related disorders and age-sensitive traits, particularly those caused by senescence-inducing stimuli, wherein the models comprise transgenes selectively expressed by senescent cells. The disclosure further provides methods for identifying therapeutic agents effective for treating or preventing age-related disorders and age-sensitive traits using the animal models, therapeutic agents identified using such methods, pharmaceutical compositions comprising the identified therapeutic agents, and methods of treating or preventing age-related disorders and age-sensitive traits.

Nucleic acid construct with a p16 promoter that causes a prodrug converting enzyme to be expressed specifically in senescent cells

Compositions of matter for treatment of ophthalmic conditions by selectively removing senescent cells from the eye

Unit dose of an aryl sulfonamide that is effective for treating eye disease and averting potential vision loss

Foamy macrophages with senescence markers accumulate in the subendothelial space at the onset of atherosclerosis where they drive pathology by increasing expression of key atherogenic and inflammatory cytokines and chemokines. In advanced lesions, senescent cells promote features of plaque instability, including elastic fiber degradation and fibrous cap thinning, by heightening metalloprotease production. This invention provides methods and materials for treating arthritis by removing senescent cells in or around atherosclerotic plaques, thereby stabilizing the plaques, inhibiting rupture of the plaques and pathological sequelae that manifest as coronary artery disease.

Treating atherosclerosis by removing senescent foam cell macrophages from atherosclerotic plaques

Use of sulfonamide inhibitors of BCL-2 and BCL-xL to treat ophthalmic disease by selectively removing senescent cells

Provided herein are immunogenic compositions (vaccines) and methods for immunizing a subject with the immunogenic compositions for inducing an adaptive immune response directed specifically against senescent cells for treatment and prophylaxis of age-related diseases and disorders, and other diseases and disorders associated with or exacerbated by the presence of senescent cells. The immunogenic compositions provided herein comprise at least one or more senescent cell-associated antigens, polynucleotides encoding senescent cell-associated antigens, and recombinant expression vectors comprising the polynucleotides for use in administering to a subject in need thereof.

Immunogenic compositions for inducing an immune response for elimination of senescent cells

Treating pulmonary conditions by selectively removing senescent cells from the lung using an intermittent dosing regimen

Method of optimizing conditions for selectively removing a plurality of senescent cells from a tissue or a mixed cell population

This disclosure provides a technology for managing the sensation of pain in a subject in need thereof. Treatment methods according to this invention include administering to the subject a formulation that contains an effective amount of (4-[(4S,5R)-4,5-bis(4-chlorophenyl)-4,5-dihydro-2-[4-methoxy-2-(1-methylethoxy)phenyl]-1H-imidazol-1-yl]carbonyl]-2-piperazinone).

Treatment of joint pain

Treatment of ophthalmic conditions by selectively removing senescent cells from the eye

Growing community of inventors

Berkeley, CA, United States of America

Judith Campisi