Institute News

Experts exchange advances in the science of healthier aging in San Diego

AuthorGreg Calhoun

Date

April 1, 2025

Sanford Burnham Prebys graduate student Tatiana Moreno presented at the 2025 La Jolla Aging Meeting. She detailed her studies regarding aging and the body’s cellular recycling system, a process called autophagy.

Two scientific meetings in late March brought together researchers studying aging and its implications for disease

Scientists from San Diego and across the United States gathered March 26-27, 2025, to discuss the latest advancements in aging research. The NIH-funded San Diego Nathan Shock Center, a collaboration among the Salk Institute for Biological Studies, Sanford Burnham Prebys and the University of California San Diego, opened the two scientific meetings with its 2025 symposium on Wednesday, March 26, at the Salk Institute in the Conrad T. Prebys Auditorium in La Jolla.

The event focused on the center’s primary research area, “The Heterogeneity of Aging.” Just as people and organisms age at different rates, scientists have demonstrated that tissues also age at their own speeds – even some cells within tissues age at a unique pace. This phenomenon, known as heterogeneity of aging, is of great interest to researchers as it may hold clues for how to develop interventions that enable people to lead healthier lives as they age.

The San Diego Nathan Shock Center Symposium convened 193 in-person attendees and another 113 virtual participants over Zoom.

Shanshan Yin, PhD, a postdoctoral associate in the lab of Peter D. Adams, PhD, director and professor in the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys, presented an update on her research regarding breast cancer and aging. She discussed results from investigating changes in gene expression and immune system activity in breast cancer tumors as mice age, leading to increased cancer incidence. Yin was awarded a San Diego Nathan Shock Center pilot grant in 2023.

The 8^th annual La Jolla Aging Meeting was held on Thursday, March 27, also in Salk’s Conrad T. Prebys Auditorium. The event brought together 257 in-person attendees and featured mostly short talks from San Diego-based postdoctoral fellows and students researching the biology of aging.

Kelly Yichen Li, PhD, a postdoctoral associate in the lab of Kevin Yip, PhD, interim director of the Center for Data Sciences and professor in the Cancer Genome and Epigenetics Program, delivered a talk regarding her work on zombie-like senescent cells that persist but no longer divide like most normal cells. Li discussed her work exploring cell types in samples of liver tissue. She discovered differences in cell composition and gene expression based on the age of the samples. Li and her collaborators continue to work on methods to identify senescent cells in tissue samples, which would accelerate research in the field.

Tatiana Moreno, a graduate student in the lab of Caroline Kumsta, PhD, associate dean of Student Affairs in the Graduate School of Biomedical Sciences and assistant professor in the Center for Cardiovascular and Muscular Diseases, detailed her studies regarding aging and the body’s cellular recycling system, a process called autophagy. Moreno discussed her findings measuring autophagy in blood samples drawn from human volunteers of various ages, including results regarding the effects of a 12-week exercise program.

Rouven Arnold, PhD, a postdoctoral associate in the Adams lab at Sanford Burnham Prebys, presented his work seeking to better understand how aging can lead to a loss of the unique cellular identity that allows cells to carry out specialized functions in different organs. Arnold focused on the HIRA protein, one of the histone chaperones responsible for helping to build spools out of histones used to hold DNA like a thread. Following studies of HIRA’s role in the aging liver, his results suggest that HIRA plays a protective role to preserve liver cell identity and promote healthy aging in the liver.

Alessandra Sacco, PhD, professor and director of the Development, Aging and Regeneration Program in the Center for Cardiovascular and Muscular Diseases at Sanford Burnham Prebys, and dean of the institute’s Graduate School of Biomedical Sciences, was a cohost for both events. Adams was a cohost for the La Jolla Aging Meeting.

About the San Diego Nathan Shock Center
The San Diego Nathan Shock Center (SD-NSC), led by Gerald Shadel, PhD, Audrey Geisel Chair in Biomedical Science and professor in the Molecular and Cell Biology Laboratory at the Salk Institute, was established in the fall of 2020 with the overall goal of understanding the heterogeneity of aging in order to allow development of personalized interventions to increase the number of years of healthy life.

To this end, the center provides three novel scientific Research Resource Cores to develop new human cell models of aging and enable the integrated analysis of molecular, cellular and tissue heterogeneity. The SD-NSC also supports and advocates basic biology of aging research in general through the development, training and mentoring activities of a Research Development Core and robust outreach efforts. All of these activities are accomplished via a consortium of three premier research institutions on the La Jolla Research Mesa: the Salk Institute for Biological Studies, Sanford Burnham Prebys and the University of California San Diego.

Alessandra Sacco serves as director of the SD-NSC Research Development Core and Peter Adams serves as co-director of the SD-NSC Heterogeneity of Aging Core.

Institute News

Registration open for San Diego aging research meetings in March

AuthorGreg Calhoun

Date

March 12, 2025

There are two exciting opportunities in March for individuals interested in learning more about aging research conducted in San Diego and across the country.

San Diego Nathan Shock Center Symposium

On Wednesday, March 26, 2025, the San Diego Nathan Shock Center will hold its annual symposium on “The Heterogeneity of Aging” at the Salk Institute in the Conrad T. Prebys Auditorium and on Zoom. Speakers and topics for the event include:

Hongkui Zeng, PhD, Allen Institute for Brain Science – “Dynamic changes of cell types in the aging brain”
Tony Wyss-Coray, PhD, Stanford University – “Young blood for old brains and the quest to slow aging”
Adam Salmon, PhD, Barshop Institute at UT Health San Antonio – “Understanding the translational potential of geroscience from cells to primates”
Lingyan Shi, PhD, University of California San Diego – “Optical Metabolic Nanoscopy for Studying Aging and Diseases”

More information is available on the symposium website.

La Jolla Aging Meeting

The La Jolla Aging Meeting follows the next day on Thursday, March 27, 2025. It also will be held at the Salk Institute in the Conrad T. Prebys Auditorium. The event will include scientific presentations and networking with a focus on postdoctoral researchers and students.

Nathan Le Brasseur, PhD, director of the Robert and Arlene Kogod Center on Aging at the Mayo Clinic, will present the keynote address.

More information is available on the meeting website.

Alessandra Sacco, PhD, professor in the Center for Cardiovascular and Muscular Diseases at Sanford Burnham Prebys, and dean of the institute’s Graduate School of Biomedical Sciences, is a cohost for both events. Peter D. Adams, PhD, director and professor in the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys, is a cohost for the La Jolla Aging Meeting.

Alessandra Sacco serves as director of the SD-NSC Research Development Core and Peter Adams serves as codirector of the SD-NSC Heterogeneity of Aging Core.

Institute News

A monster, MASH

AuthorGreg Calhoun

Date

January 28, 2025

3D illustration of liver cancer.

Scientists show how the advanced form of fatty liver disease has monstrous effects on liver cancer risk

Liver cancer has proven to be a tough beast to tame. Experts expected rates of the cancer to decrease following the development of the hepatitis B vaccine in the 1980s, which reduced one of the major risk factors for the disease.

Research in Taiwan showed that its universal infant hepatitis B vaccination program led to young adults experiencing a 35.9% reduction in cases of hepatocellular carcinoma (HCC), the most common liver cancer.

Despite innovation leading to the world’s first cancer-preventing vaccine, incidence of HCC has been on the rise due to a spike in fatty liver disease over recent decades. Lifestyle factors such as high-calorie diets, excessive alcohol consumption and minimal exercise — along with genetic predispositions — can lead to problematic changes in the liver, heart and kidneys.

Specifically in the liver, growing deposits of fat in the tissue can lead over time to an advanced form of fatty liver disease marked by chronic inflammation and the accumulation of thickened scar tissue, a condition known as metabolic-associated steatohepatitis (MASH). MASH significantly increases a patient’s risk of developing HCC.

Debanjan Dhar, PhD, is an associate professor in the Cancer Genome and Epigenetics Program.

In a paper published January 1, 2025, in Nature, scientists at Sanford Burnham Prebys, the University of California San Diego, Curtin University, the University of Pennsylvania and The Liver Cancer Collaborative, demonstrated that MASH damages the DNA of liver cells. The study also linked these changes to the development of liver cancer.

Peter Adams, PhD, is the director of the Cancer Genome and Epigenetics Program.

“DNA damage from MASH causes liver cells to stop dividing and enter a zombie-like state called senescence,” said Debanjan Dhar, PhD, associate professor in the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys and coauthor on the study. “This study’s results demonstrate that some of these cells later exit senescence and are likely to become cancerous due to their accumulation of damage and mutations.”

“In the future, we can apply what we’ve learned to study potential opportunities to prevent or repair DNA damage from MASH to reduce patients’ risk of developing liver cancer,” said Peter Adams, PhD, director of the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys and coauthor on the study.

Michael Karin, PhD, Distinguished Professor in the Department of Pharmacology at the University of California San Diego School of Medicine, is the senior and corresponding author on the study.

Li Gu, PhD, a former postdoctoral fellow in the Karin lab, shares first authorship of the study with visiting scientist Yahui Zhu.

Additional authors include:

Marcos Teneche and Souradipta Ganguly from Sanford Burnham Prebys
Shuvro Nandi, Maiya Lee, Kosuke Watari, Breanna Bareng, Masafumi Ohira, Yuxiao Liu, Sadatsugu Sakane, Mojgan Hosseini, Tatiana Kisseleva, Ludmil Alexandrov, Consuelo Sauceda and David Gonzalez from the University of California San Diego
Rodrigo Carlessi and Janina Tirnitz-Parker from Curtin Universit
The Liver Cancer Collaborative
M. Celeste Simon from the University of Pennsylvania

Institute News

Bile may be key to immunotherapy effectiveness in liver cancer

AuthorGreg Calhoun

Date

January 17, 2025

A 3D illustration of hepatocellular carcinoma, the most common liver cancer.

Understanding the crucial ingredient in bile may unlock the potential of treatments that help patients’ immune systems eliminate cancer

Hepatocellular carcinoma (HCC) is the most common liver cancer and a growing threat to public health across the globe due to the rising rate of fatty liver disease.

Liver cancer is difficult to treat as it often causes few if any symptoms early on, so it tends to be diagnosed at later, more aggressive stages. While immunotherapies that supercharge patients’ immune systems have proven effective in some cancers, this approach has had limited success in patients suffering from HCC or other forms of the disease.

Scientists are investigating the unique qualities of different tissues that may explain why the effectiveness of immunotherapy varies depending on the location of a tumor. The liver is known to have a flexible immune system capable of defending itself when necessary while not overreacting to a constant flood of foreign materials from digesting food, including metabolic byproducts from bacteria residing in the gut microbiome.

Transplant surgeons see the unique properties of the liver’s immune system firsthand when transplanted livers are typically integrated by recipients with only a low dose of immunosuppressive drugs. This ability to maintain immune tolerance, however, may reduce the ability of the liver’s immune system to find and destroy cancer cells, even when that capability is enhanced by immunotherapy.

In a paper published January 9, 2025, in Science, scientists at Sanford Burnham Prebys, the Salk Institute, the University of California San Diego, Columbia University Irving Medical Center, Memorial Sloan Kettering Cancer Center and the Geisel School of Medicine at Dartmouth, found that a critical ingredient in bile hinders the liver’s immune response against cancer.

Bile is a fluid made by the liver that assists in breaking down fats during digestion. This function is made possible by steroidal acids known as bile acids. The scientists found an increased amount of bile acids in tumor samples from patients with HCC. The team also found that genes involved in creating bile acids were being transcribed to make proteins and enzymes at an abnormally high rate in human samples and in mice genetically modified to develop liver cancer.

The authors went on to remove genes related to bile acid construction to demonstrate that mice without these blueprints developed fewer, smaller tumors. In addition, the liver’s T cells — the primary anti-tumor immune cells — were able to dig deeper into tumors and persist for longer without the immunosuppressive effects of certain bile acids.

“These findings underscore a new appreciation for the influence of bile acids on the liver’s immune system,” said Debanjan Dhar, PhD, associate professor in the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys and coauthor on the study. More research is needed to test the potential use of drugs to directly inhibit certain bile acids or bile acid receptors as a therapeutic strategy to reduce liver cancer growth.

Debanjan Dhar, PhD, is an associate professor in the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys.

Peter Adams, PhD, is the director of the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys.

It may also be possible to achieve this effect through dietary changes that alter the microbiome and result in modified bile acid production. Based on their findings, the research team suggests that this could be done by using ursodeoxycholic acid, a bile acid that currently is used to treat an autoimmune condition called primary biliary cholangitis. The acid is found at high levels in bear bile, which has served for thousands of years as a treatment in traditional Chinese medicine.

“Given the safety profile of ursodeoxycholic acid and the limited effectiveness of immunotherapy on liver cancer, this study shows significant potential for testing this bile acid as a combination treatment for patients with HCC,” said Peter Adams, PhD, director of the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys and coauthor on the study.

Susan Kaech, PhD, NOMIS Chair, professor and director of the NOMIS Center for Immunobiology and Microbial Pathogenesis at the Salk Institute is the senior and corresponding author on the study.

Siva Karthik Varanasi, PhD, assistant professor at the UMass Chan Medical School and a former postdoctoral fellow in the Kaech lab at the Salk Institute, is first author on the manuscript.

Additional authors include:

Souradipta Ganguly, Marcos G. Teneche and Aaron Havas, from Sanford Burnham Prebys
Dan Chen, Melissa A. Johnson, Kathryn Lande, Michael A. LaPorta, Filipe Araujo Hoffmann, Thomas H. Mann, Eduardo Casillas, Kailash C. Mangalhara, Varsha Mathew, Ming Sun, Yagmur Farsakoglu, Timothy Chen, Bianca Parisi, Shaunak Deota, H. Kay Chung, Satchidananda Panda, April E. Williams and Gerald S. Shadel, from the Salk Institute
Yingluo Liu, Cayla M. Miller, Jin Lee and Gen-Sheng Feng, from the University of California San Diego
Isaac J. Jensen and Donna L. Farber, from Columbia University Irving Medical Center
Andrea Schietinger from Memorial Sloan Kettering Cancer Center
Mark S. Sundrud from the Geisel School of Medicine at Dartmouth

Wolfram Goessling, MD, PhD, the Robert H. Ebert Associate Professor of Medicine and associate professor of Health Sciences and Technology at Harvard Medical School, authored a Perspective article on the new study in Science called, “Ena-bile-ing liver cancer growth.”

Institute News

A Conversation About Aging and Cancer at Sanford Burnham Prebys

AuthorGreg Calhoun

Date

October 24, 2024

Event recording now available for panel discussion with scientists held on October 9, 2024

David A. Brenner, MD, president and CEO of Sanford Burnham Prebys, welcomed attendees to the launch of a new community engagement program called “A Conversation About” in the institute’s Victor E. LaFave III Memorial Auditorium on October 9, 2024.

The initial panel discussion in the A Conversation About series focused on the connection between aging and cancer and included information about a current breast cancer research collaboration. A recording of the event is available online.

Reena Horowitz, the founder of Group of 12 and Friends at Sanford Burnham Prebys, provided introductory remarks. Brooke Emerling, PhD, director of the Cancer Metabolism and Microenvironment Program, moderated the discussion among three featured panelists:

Peter Adams, PhD, director of the Cancer Genome and Epigenetics Program, Sanford Burnham Prebys
Xiao Tian, PhD, assistant professor in the Degenerative Diseases Program, Sanford Burnham Prebys
Kay Yeung, MD, PhD, associate clinical professor in the Division of Hematology-Oncology, University of California San Diego Health

By bringing together community collaborators and clinicians with Sanford Burnham Prebys researchers, A Conversation About offers a unique perspective on how clinical research and practice can be used to inform fundamental and translational science.

Watch Event Recording

Institute News

San Diego hosts the 2024 Molecular and Cellular Aging Meeting

AuthorGreg Calhoun

Date

September 19, 2024

Alex Cagan, PhD, a scientist and illustrator at the University of Cambridge and the Wellcome Sanger Institute, created live illustrated summaries of talks at the 2024 Molecular and Cellular Aging Meeting.

Sanford Burnham Prebys scientist Peter Adams planned the symposium in partnership with colleagues at the University of California San Diego and Altos Labs.

Researchers gathered in San Diego from September 10-11 to discuss their research findings on the causes and complications of aging at the level of the trillions of cells in our bodies—and the vast array of molecules within each cell.

Peter D. Adams, Ph D, the director of the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys, was one of the planners of the meeting, which was held at the Estancia La Jolla Hotel and Spa. Adams’ co-planners were Bing Ren, PhD, professor of Cellular and Molecular Medicine at the University of California San Diego, and Morgan Levine, PhD, founding principal investigator at the Altos Labs’ San Diego Institute of Science.

Before the 2024 Molecular and Cellular Aging Meeting kicked off, attendees were welcomed to join the final proceedings of a related meeting of the Cellular Senescence Network (SenNet) Consortium, a large network of U.S. labs and research institutions supported by the National Institutes of Health’s Common Fund.

Adams introduced Ashley Webb, PhD, associate professor at the Buck Institute for Research on Aging in Novato, Calif., to give the SenNet meeting’s Judy Campisi Lecture Series keynote address. This series of lectures honors Campisi’s legacy as a leader in the field of cellular senescence, a phenomenon closely tied with aging in which certain cells stop growing and dividing yet persist in a zombie-like state.

Following Webb’s lecture, Adams formally opened the 2024 Molecular and Cellular Aging Meeting. The event featured more than a dozen presentations and several poster sessions.

illustration of Nancy Zhang's talk by Alex Cagan — Artistic interpretation of the presentation delivered by Nancy R. Zhang, PhD, Ge Li and Ning Zhao Professor, a professor of Statistics and Data Science and the vice dean of Wharton Doctoral Programs at the University of Pennsylvania. Image courtesy of Alex Cagan.

“I was excited to see the room so full in anticipation of the great talks and all the fantastic questions and discussion that followed,” said Adams.

“I am happy that we achieved our goal of bringing together SenNet reseachers and other leaders in the molecular and cellular biology of aging. I expect that this catalyzed many new ideas and collaborations.”

Speakers at the event included:

Vittorio Sebastiano, PhD, associate professor of Obstetrics and Gynecology (Reproductive and Stem Cell Biology), Stanford University School of Medicine, “Looking at aging and rejuvenation through the lens of development and reproductive biology”
Zhijian “James” Chen, PhD, Howard Hughes Medical Institute investigator, George L. MacGregor Distinguished Chair in Biomedical Science and professor of Molecular Biology, University of Texas Southwestern Medical Center, “Igniting the flame—the role of cGAS in senescence and inflammaging”
Vera Gorbunova, PhD, Doris Johns Cherry Professor and professor of Biology, University of Rochester, “Epigenome maintenance and longevity”
Jan Karlseder, PhD, senior vice president, chief science officer, professor in the Molecular and Cell Biology Laboratory and Donald and Darlene Shiley Chair, Salk Institute, “How telomeres synergize with mitochondria to prevent age associated cancer initiation”
Shelley L. Berger, PhD, Daniel S. Och University Professor, University of Pennsylvania, “Epigenetic-metabolic crosstalk in senescence and aging” 
Levine, “Origins of Life and Death: Aging as an Out-of-Distribution Problem”
Adams, “The role of aging in cancer”
Kun Zhang, PhD, principal investigator, Altos Labs’ San Diego Institute of Science, “An aging and injury cell atlas of human kidneys”
Nancy R. Zhang, PhD, Ge Li and Ning Zhao Professor, professor of Statistics and Data Science and vice dean of Wharton Doctoral Programs, University of Pennsylvania, “Transcriptomic signatures of senescence and aging” 
Alex Cagan, PhD, assistant professor of Genetics, Pathology and Veterinary Medicine, University of Cambridge, “Somatic evolution and ageing across the tree of life”
Congcong He, PhD, associate professor of Cell and Developmental Biology, Northwestern University Feinberg School of Medicine, “Exercise-induced autophagic protection against age-related metabolic diseases”
Gerald Shadel, PhD, professor in the Molecular and Cell Biology Laboratory, Audrey Geisel Chair in Biomedical Science and director of the San Diego-Nathan Shock Center of Excellence in the Basic Biology of Aging, Salk Institute, “Mitochondrial stress signaling in aging, disease and immunity”

Peter Adams, PhD

Bing Ren, PhD

Morgan Levine, PhD

Institute News

Peter Adams named Mentor of the Year at 21st Annual Research Trainee Symposium

AuthorMiles Martin

Date

September 23, 2022

Peter Adams, PhD, has been named Mentor of the Year, a new honor from the Institute’s Office of Education, Training and International Services (OETIS) and the Postdoctoral Training Advisory Group (PTAG).

The award was based on nomination letters submitted by postdocs and graduate students on the Sanford Burnham Prebys campus, and the winner was selected by a committee of PTAG members. The award was announced on September 22 at the 21st Annual Trainee Research Symposium.

“Professor Adams creates an environment that supports his postdocs in pursuing their research projects by motivating his trainees to experience new techniques, take on challenging projects and help them to decide the direction in which they want to move forward,” said postdoctoral associate Marie Berenguer, who presented the award to Adams. “He helps his trainees expand their professional networks and further develop their technical and transferable skills. Every trainee from the Adams lab submitted an abstract for this year’s Annual Trainee Research Symposium, a sign of Peter’s commitment to their training.”

trainees and posters — Trainees present their research to peers and faculty at the poster session

In his comments when accepting the award, Adams spoke to his mentoring philosophy: “Some of you have asked me, ‘What’s the most important thing in a student or a postdoc?’ What I’ll say is that the most important thing is to take ownership of your project, so my mentoring strategy is, in a way, to put the burden on you. But I can only put that burden on you if you can rise to it and take that on, and clearly you do. You do a great job, so that makes my life very easy.”

Reading from nomination letters submitted by postdocs, Berenguer added, “Your positive vision and passion for science, your willingness to collaborate and help, and your kind personality were highly praised and stated as the major reason that you are a one-of-a-kind mentor who has positively impacted your lab members and also many other researchers across Sanford Burnham Prebys.”

In addition to the award presentation, the day consisted of opening remarks from Hudson Freeze, PhD, and Alessandra Sacco, PhD; presentations by graduate students and postdocs from labs across the Institute; and a keynote presentation from Principal Investigator Karissa Sanbonmatsu, PhD, from Los Alamos National Laboratories, about her work in epigenetics. President and CEO David Brenner, MD, delivered closing remarks, which were followed by a poster session.

“Mentoring is one of the most important things senior faculty can do to advance the careers of their students and postdocs,” said Brenner during his comments. “It’s such a pleasure to join you all for this symposium today.”

trainees and faculty enjoying refreshments — Trainees and faculty enjoy refreshments during a break

Institute News

How misplaced DNA contributes to chronic illness

AuthorMiles Martin

Date

October 28, 2021

Though DNA is essential for life, it can also wreak havoc on our bodies as we age

DNA is one of the essential building blocks of life, giving our cells instructions for virtually everything they do, but researchers at Sanford Burnham Prebys are investigating what happens to our cells when DNA ends up in places where it shouldn’t normally be, particularly as we age.

The answer – as described in their recent review in the journal Cell—is disease-causing inflammation. And the researchers hope that targeting this rogue DNA will lead to new therapeutic strategies for a range of age-related illnesses, including cancer, diabetes, rheumatoid arthritis, cardiovascular disease and neurodegenerative disorders.

“Age is the primary risk factor for all of these diseases, but they share another risk factor – chronic inflammation,” says first author Karl Miller, PhD, a postdoctoral researcher in the lab of Peter Adams, PhD, Sanford Burnham Prebys. “We’re trying to understand the underlying processes behind this inflammation so we can potentially treat all these age-related diseases together”

Typically, cells have DNA safely sequestered in their nucleus and in the mitochondria, where the DNA can do its job without interfering with the rest of the cells’ activities. When cells detect DNA in other areas, they unleash a series of biochemical responses designed to protect the cell from invaders. This response is a component of the innate immune system, our body’s first line of defense against infection.

Scientists have known about this system for decades, but until recently it was mostly thought to respond to foreign DNA, such as during a bacterial or viral infection. However, over the last decade, researchers have discovered that pieces of our own DNA, called endogenous cytoplasmic DNA, can escape from the nucleus or mitochondria and trigger this inflammatory response in our own cells, even in the absence of infection. The resulting ‘sterile’ inflammation can accumulate over time, contributing to a range of age-related diseases in all systems of the body.

But this inflammation is not without its upsides. Cytoplasmic DNA is actually an important short-term protective strategy against cancer formation. The inflammation can alert the immune system at the first sign of cancer, preventing its formation. But over the long term, the sterile inflammation caused by cytoplasmic DNA is also thought to contribute to cancer risk. In fact, we’ve only been able to observe the damage associated with sterile inflammation because people are now living long enough to experience it.

“Systems like this exist because they’re beneficial in youth, but as we age, they break down,” says Miller. “100 years ago, a lot more people died from infectious diseases early in life. Over time, we’ve become better and better at treating these acute infections, and we’re living much longer. It’s in this later period in life that we see chronic diseases emerging that used to be much less common.”

Miller’s review describes four different types of cytoplasmic DNA fragments, classified according to when and how they appear. Some arise from the nucleus during mistakes in cell division. Others emerge because of errors in DNA repair or replication. Some even escape from mitochondria—energy-producing parts of the cell that have their own separate DNA. Others still are of unknown origin.

“They all look similar under a microscope, and they all can cause similar effects. That’s one of the major problems in this field. The benefit of studying how the different types emerge is that it gives us more points to target for therapeutics,” says Miller.

In the Adams Lab, Miller and his colleagues look specifically at cytoplasmic chromatin fragments, one of the four types of cytoplasmic DNA. These fragments appear in the cell when the membrane surrounding the nucleus is weakened by senescence, a cellular stress response. Senescence is also associated with aging.

“We’ve shown how this pathway works in mice, and now we’re actually moving forward with therapeutic applications for humans by doing drug screening to find compounds that can target it,” adds Miller.

And while there is still a lot of work left for the researchers, their progress is encouraging. Adams, senior author on the Cell review, was recently awarded a $13 million grant by the NIH to study the effects of aging, including the role of cytoplasmic DNA, on the progression of liver cancer.

“We like to call what we’re doing here ‘increasing the healthspan’, as opposed to the lifespan,” says Miller. “We’re hoping to maximize the healthy period of people’s lives.”

Institute News

Top San Diego researchers receive $5 million to study cellular aging

Authorsgammon

Date

September 22, 2020

Professors Peter Adams, PhD, and Malene Hansen, PhD, of Sanford Burnham Prebys will lead key research and development cores

Sanford Burnham Prebys researchers are joining forces with University of California San Diego (UC San Diego) and the Salk Institute to form a world-class San Diego Nathan Shock Center (SD-NSC), a consortium established to study cellular and tissue aging in humans. The center will be funded by the National Institute on Aging (NIA), part of the National Institutes of Health, and is expected to receive $5 million over the next two years.

Professors Peter Adams, Ph.D., and Malene Hansen, PhD, of Sanford Burnham Prebys will lead key research and development cores, along with Professors Rusty Gage, PhD, Martin Hetzer, PhD, and Tatyana Sharpee, PhD, of Salk; and Anthony Molina, PhD, of UC San Diego. Salk Professor Gerald Shadel, PhD, will be the director of the SD-NSC.

“This is a special opportunity for San Diego’s aging research community to share our ideas, skills and technologies to drive innovative research in the basic biology of aging,” says Adams. “We are grateful for this support and will work to create the strongest environment possible to achieve meaningful breakthroughs that will benefit human health.”

Aging is the most significant risk factor for human disease. Human cells and tissues age at different rates depending on their intrinsic properties, where they are in the body and environment exposures. Yet, scientists do not fully understand this variability (“heterogeneity”) and how it contributes to overall human aging, risk for disease or therapeutic responses.

To explore the complex heterogeneity of human aging, the SD-NSC will deploy three cutting-edge Research Resource Cores, including the Human Cell Models of Aging Core, to be led by Gage and Molina; the Heterogeneity of Aging Core, to be led by Hetzer and Adams; and the Integrative Models of Aging Core, to be led by Sharpee.

The cores will allow detailed analysis of human cells and organoids (artificially grown clusters of cells that model tissues), derived from a unique aging cohort at UC San Diego that is annotated for multiple measures of the actual biological age of individuals. In addition, the cores will provide scientific services to the Nathan Shock Centers network and the aging research community at large, including the dissemination of samples, protocols and computational tools to facilitate the study of heterogeneity in aging.

A Research Development Core headed by Hansen will also be established to encourage and support new investigators to enter the field of aging research. Through this core, the SD-NSC will provide pilot research grants, workshops and customized mentoring programs to promote the research and development of young investigators, as well as in-person and virtual trainings to spur collaboration and the sharing of knowledge related to the basic biology of aging.

“For years, my colleagues and I have been organizing successful symposia such as the annual La Jolla Aging Meeting (LJAM), where we share new aging research and discuss opportunities for collaboration,” says Hansen, who also hold the positions of associate dean for Student Affairs and faculty adviser for Postdoctoral Training at Sanford Burnham Prebys. “The San Diego Nathan Shock Center will enable us to broaden the reach and impact of LJAM, as well as take training and mentoring of the next generation of researchers to a new level.”

The SD-NSC builds on Sanford Burnham Prebys’ strengths in fundamental aging research, renowned for its use of model organisms to unravel cell changes associated with normal development and aging. By building, analyzing and probing models of disease, scientists in the Institute’s Aging, Development and Regeneration Program are providing new tools to uncover novel therapeutic targets for heart disease, neurodegeneration, muscle disorders, diabetes, cancer and other debilitating diseases.

The SD-NSC will be one of a network of eight Nathan Shock Centers nationwide, and is funded by NIA grant number P30AG068635.

Institute News

“We are desperate for new therapies”

AuthorMonica May

Date

September 23, 2019

Experts discuss AML during the Sanford Burnham Prebys community lecture series

Bill Veljovich had never been sick in his life. “Not even joint pain,” shared the 80-year-old retired engineer at our recent Fleet Science Center discussion about acute myeloid leukemia (AML), a life-threatening type of blood cancer. He was joined by experts from Sanford Burnham Prebys and UC San Diego Health.

However, his doctor noticed that his white blood cells counts were off during a routine blood test. He was diagnosed with a blood cancer called myelodysplastic syndrome (MDS), which progressed to AML (this occurs in one out of three people with MDS). Fortunately, Veljovich responded well to a then off-label treatment that only recently was approved for older patients with AML.

“The truth is, we are desperate for new therapies,” said speaker Rafael Bejar, MD, PhD, a clinician at UC San Diego who specializes in blood cancers. “AML typically occurs in people over the age of 60, who often aren’t able to tolerate intensive chemotherapies.”

Until two years ago, the treatments for AML remained the same as those used in the 1970s: a chemotherapy combination and perhaps a bone marrow transplant. Only 24% of adults with AML remained alive five years after treatment.

Now, thanks to foundational research that revealed the underlying genetic drivers of AML, eight new drugs have been approved in the past two years. Several more targeted therapies are nearing potential FDA approval.

However, AML, which usually arises in cells that turn into white blood cells, is an incredibly complex and fragmented disease. Genome sequencing has revealed that more than 30 genes drive the cancer. Many different treatment types will be needed to truly conquer AML.

Peter Adams, PhD, a professor in Sanford Burnham Prebys’ National Cancer Institute (NCI)-designated Cancer Center, hopes to find a treatment that works for a broader AML population. He focuses on a protein called p53, often called the “guardian of our genome.” This protein senses DNA damage and kills the faulty cell—protecting us from developing cancer. However, to scientists’ surprise, 90% of people with AML have a normal p53 gene.

“Emerging research suggests that AML inactivates p53 through other means,” said Adams. “My team is working to develop a drug combination that could reactivate the protective powers of p53—and thus fight AML.”

New research advances can’t come soon enough for people living with the cancer.

“I’ve always taken the approach of learning as much as possible—and then fixing the problem,” said Veljovich, who designed and tested rocket engines before he retired. “I have learned that blood cancers are extremely complex. I wish there was a simple solution, but there isn’t. I’m grateful that we have smart folks like Dr. Bejar and Professor Adams who are working on these tough problems to find better medicines for AML.”

This event was the second of our five-part “Cornering Cancer” series. Join us for discussions on breast cancer (October 20), pancreatic cancer (November 17) and pediatric brain cancer (December 8). Register today.

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