In May 2024, Matt delivered a talk at the 2024 Glenn AFAR Grantee Conference in Santa Barbara, California and met with several people doing interesting work in the longevity field.

One of these was Aditi Gurkar, an assistant professor in the University of Pittsburgh's Aging Institute, Division of Geriatric Medicine whose lab focuses on the downstream effects of DNA damage on aging. Prior to setting up her lab at the University of Pittsburgh, Aditi conducted research on the impact of DNA damage on aging at Scripps Research. She also completed postdoctoral training at Massachusetts General Hospital/Harvard Medical School and the Broad Institute of MIT and Harvard, where she focused on the tumor suppressor p53 as well as on autophagy regulation. Aditi received a PhD and a B.S. from the Boston University School of Medicine and Florida International University in Miami respectively.

Matt and Aditi spend much of this episode chatting about senescent cells: how Aditi developed a focus on cellular senescence and found its relevance to aging, potential therapeutic benefits of senescent cell clearance, and the much-debated question of how to define a senescent cell. They also discuss the importance of "zooming out" from narrow areas of focus in the geroscience field to find new solutions and of breaking your own models on your way to productive new directions in science.

Check out the links below for further information and/or reading about some of the things we discussed in this podcast episode. Note that we do not necessarily endorse or agree with the content of these readings, but present them as supplementary material that may deepen your understanding of the topic after you listen to our podcast. This list is in no way exhaustive, but it’s a good start!

Gurkar lab

Aditi's lab at the University of Pittsburgh is broadly interested in molecular drivers of aging, and specifically tackles DNA damage and heart disease, DNA damage in post-mitotic tissue, and DNA damage-dependent metabolic reprogramming. If you might want to work with Aditi as a research specialist, technician, postdoctoral fellow, or simply want to learn more about what she works on, check out this page to find papers that have come out of the Gurkar lab, the lab's funding sources and affiliations, and more.

Cellular Senescence: The Trojan Horse in Chronic Lung Diseases

This paper, which Aditi coauthored, likens senescent cells to Trojan horses: harmless at first appearance, but potentially dangerous contributors to disease. This review discusses various known markers of senescent cells, including senescence-associated beta-galactosidase and the senescence-associated secretory phenotype, as well as potential drivers of cellular senescence. It also reviews the potential role of cellular senescence in lung disease pathogenesis and why lungs might be particularly susceptible to cellular senescence.

Cellular Senescence: Defining a Path Forward

What even is a senescent cell? As Matt notes, there doesn't seem to exist a single clear definition of a "senescent cell" even within the cellular senescence research community. This paper attempts to offer some clarity about how we might define and characterize cellular senescence, with its broadest description of the phenomenon matching Aditi's: "a prolonged and generally irreversible cell-cycle arrest". It also goes over the challenges of studying cellular senescence in humans.

Cellular senescence in aging and age-related disease: from mechanisms to therapy

This is one of the literature’s key reviews linking cellular senescence to diseases of aging. It discusses the context-dependent and heterogeneous nature of senescent cells and the resulting challenges of standardizing senescent cell markers in vivo, speculative mechanisms for how senescent cells might cause age-related tissue dysfunction, and diseases of aging in which senescent cells may play a causal role.

Aging, Cellular Senescence, and Cancer

This paper discusses various ways that cellular senescence may drive pathologies of aging, particularly in cancer. It also goes over various general characteristics of senescent cells, drivers of cellular senescence, and ways in which cellular senescence can actually be beneficial.