#112 – Ned David, Ph.D.: How cellular senescence influences aging, and what we can do about it

A company co-founded by Ned David in 2011, focused on developing medicines based on the science of cellular senescence to treat diseases of aging.

Pharmaceutical company that acquired Kythera Biopharmaceuticals.

A previous company co-founded by Ned David, focused on applying oncology and inflammatory disease biology to aesthetics, leading to the development of Kybella.

Ned David's prior company, founded in 2003.

The venture fund that provided early, patient funding to Unity Biotechnology during its stealth phase.

Ned David's first company, a high-throughput structural biology company founded during graduate school, which lacked a disciplined risk assessment approach.

A complex that acts as a master decision-maker in cells, influencing whether they divide or enter a state of resource conservation, inhibited by Rapamycin and caloric restriction.

A gene discovered in Cynthia Kenyon's screen, associated with the IGF-1 receptor signaling pathway, manipulated to extend lifespan in C. elegans.

Four specific gene products that, when expressed in cells, can artificially induce a reset cellular state, similar to an embryonic state, with implications for youthful biology.

A pro-inflammatory SASP factor that is the target of successful drugs like Humira, indicating its role in bad biology.

A biochemical pathway whose attenuation has been shown to extend lifespan in various organisms, including C. elegans and, to a lesser extent, mammals.

A class of molecules designed to selectively eliminate senescent cells from living creatures, offering a potentially safer and less frequent dosing regimen.

A SASP factor that is the target of multi-billion dollar drugs like Lucentis and Eylea, used for eye diseases and cancer.

A family of proteins that regulate apoptosis, targeted by Unity Biotechnology's molecules to selectively inhibit apoptosis inhibitors, thereby causing senescent cells to die.

A millimeter-sized worm used in Cynthia Kenyon's groundbreaking research where knockdown of a single gene doubled its lifespan.

A gene discovered in Cynthia Kenyon's screen, a transcription factor associated with the IGF-1 receptor signaling pathway, manipulated to extend lifespan in C. elegans.

A ubiquitin ligase that marks proteins, including p53, for destruction. Inhibiting Mdm2-p53 interaction can selectively kill senescent cells.

A collection of over a hundred factors secreted by senescent cells that distort tissue function and contribute to features of natural aging and age-related diseases.

A tumor suppressor protein whose concentration increases in senescent cells when its interaction with Mdm2 is inhibited, leading to selective cell death.

Scientist who, in the early 1960s, challenged the dogma that mammalian cells had infinite division capacity, coining the term 'senescent cells' and prophetically linking them to aging.

Scientist whose paper on C. elegans showed that knocking down a single gene could double the animal's lifespan, opening up the field of aging research.

Scientist whose work linked calorie restriction to Rapamycin, identifying mTOR as a common control knob for longevity.

A visionary investor from ARCH Venture Partners who supported Ned David's early efforts to fund Unity Biotechnology.

Co-founder of Unity Biotechnology and collaborator from the Mayo Clinic, whose lab genetically engineered mice to eliminate senescent cells, providing proof-of-concept for their role in aging.

Guest on the podcast and co-founder/President of Unity Biotechnology. He is a serial entrepreneur in biotechnology and a prolific innovator.

Co-founder of Unity Biotechnology and a collaborator, who discovered the first biomarker for senescent cells in vivo (1995) and the Senescence-Associated Secretory Phenotype (SASP) in 2008.

Nobel laureate who famously believed that cells from mammals had infinite capacity to divide, a belief later overturned by Leonard Hayflick's work.

A young scientist who collaborated with Jan van Deursen, publishing a paper in Science demonstrating the accumulation of senescent cells in atherosclerotic plaques in rodents.

Nobel Prize-winning scientist who identified the four factors capable of reprogramming adult cells into induced pluripotent stem cells (iPSCs).

A professor of bioengineering at Johns Hopkins who collaborated with Unity Biotechnology on developing an osteoarthritis model and testing senolytic molecules.

A scientist who has been searching for over a decade for a universal external marker of senescence cells.

Ned David's long-term business partner and CEO at Unity Biotechnology, who was also involved in founding Kythera.

A class of cholesterol-lowering drugs, mentioned as a benchmark against which PCSK9 inhibitors are compared in terms of cost-effectiveness.

A multi-billion dollar drug targeting VEGF alpha, used for diseases of the eye and cancer.

A molecule discovered on Easter Island derived from soil bacterium, found to extend life by turning the same control knob as caloric restriction, inhibiting mTOR.

A multi-billion dollar drug targeting VEGF alpha, used for diseases of the eye and cancer.

A commercial product developed by Kythera Biopharmaceuticals that causes fat cells to explode, available at dermatologists.

An anti-TNF drug, mentioned as an example of a successful drug targeting a SASP factor (TNF-alpha).

A class of drugs mentioned in the context of the challenges of drug development for atherosclerosis due to moderate uptake and high cost.