Buck Institute for Research on Aging

Mayo Foundation for Medical Education and Research

Unity Biotechnology, Inc.

The Johns Hopkins University

Erasmus University Medical Center Rotterdam

Buck Institute for Research Aging

Marco Demaria

Judith Campisi

Remi-Martin Laberge

Nathaniel E David

James L Kirkland

Tamar Tchkonia

Yi Zhu

Jan M A Van Deursen

Darren J Baker

Alain Philippe Vasserot

Albert Davalos

Bennett G Childs

Jennifer H Elisseeff

Chaekyu Kim

Okhee Jeon

Francis Rodier

James Mitchell

Jan H J Hoeijmakers

Wendy Toussaint

Jan MA Van Deursen

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

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

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

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 invention provides a transgenic mouse with a p16promoter sequence that controls expression of a protein such that it is expressed preferentially in senescent cells. The protein either directly induces apoptosis, or converts a prodrug to a cytotoxic compound. In addition, the mouse is injected with syngeneic tumor cells, or has second transgene that causes tumors to form. Removing senescent cells from the mouse may result in the formation of fewer tumors.

Transgenic mouse for determining the role of senescent cells in cancer

Growing community of inventors

Groningen, Netherlands

Marco Demaria