Mayo Foundation for Medical Education and Research

Unity Biotechnology, Inc.

Buck Institute for Research on Aging

The Johns Hopkins University

Buck Institute for Research Aging

Jan M A Van Deursen

Nathaniel E David

Remi-Martin Laberge

James L Kirkland

Tamar Tchkonia

Darren J Baker

Judith Campisi

Yi Zhu

Marco Demaria

Bennett G Childs

Alain Philippe Vasserot

Albert Davalos

Jennifer H Elisseeff

Chaekyu Kim

Okhee Jeon

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 cardiovascular disease by selectively eliminating senescent cells

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

Removing senescent cells from a mixed cell population or tissue using a phosphoinositide 3-kinase (PI3K) inhibitor

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

Methods and compositions for killing senescent cells and for treating senescence-associated diseases and disorders using an inhibitor of Akt kinase

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

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

This document relates to methods and materials involved in the removal of senescent cells within a mammal. For example, transgenic non-human animals that can be induced to delete senescent cells are provided.

Increasing healthy lifespan and delaying progression of age-related phenotypes by selectively removing senescent cells

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

Treatment for osteoarthritis in a joint by administering a means for inhibiting MDM2

Use of sulfonamide inhibitors of Bcl-2 to treat senescence-associated lung conditions such as pulmonary fibrosis and chronic obstructive pulmonary disease

This document provides a transgenic mouse for studying the role of senescent cells in an age-related phenotype. A recombinant polypeptide is expressed in senescent cells under control of a p16INK4a promoter. The polypeptide can be triggered to directly induce cell death in senescent cells. As a result, progression of one or more age-related phenotypes is delayed in the mouse. An example is the INK-ATTAC mouse which also expresses a marker polypeptide in senescent cells.

Transgenic animals capable of being induced to delete senescent cells

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Rochester, MN, United States of America

Jan M A Van Deursen