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Top Sanford Burnham Prebys research stories of 2021

AuthorSusan Gammon
Date

December 14, 2021

top 10 sign

This year’s most popular research stories include scientific breakthroughs in COVID-19, cancer, schizophrenia and more.

As we bid farewell to 2021, let’s celebrate our most newsworthy research breakthroughs. Despite the continuing challenges brought on by COVID-19, Sanford Burnham Prebys achieved important milestones on the frontiers of biomedical science.

The following 10 research-related stories received top views on Newswise—the press release distribution service for journalists seeking health and science news.
 

  1. COVID-19: Scientists identify human genes that fight infection
    A research team was able to pinpoint specific human genes that control viral infection. The information sheds new light on factors that lead to severe disease and guides therapeutic options.
     
  2. Tumor marker may help overcome endocrine treatment-resistant breast cancer
    The study discovered a new approach to select breast cancer patients for HER2 therapy and could help individuals avoid disease relapse or progression of endocrine-sensitive disease.
     
  3. Scientists identify potential drug candidates for deadly pediatric leukemia
    Two existing drugs—JAK inhibitors and Mepron—show promise for a subtype of acute myeloid leukemia (AML) that is more common in children. The drugs are proven safe in humans, which could accelerate clinical studies.
     
  4. Leprosy drug holds promise as at-home treatment for COVID-19
    Scientists found that the leprosy drug clofazimine, which is FDA approved and on the World Health Organization’s List of Essential Medicines, exhibits potent antiviral activities against SARS-CoV-2, and could become an important weapon against future pandemics.
     
  5. Researchers dig deeper into how cells transport their waste for recycling
    Research describing how the “trash bags” in a cell—called autophagosomes—are tagged for recycling opened new paths to understand age-related diseases such as cancer and neurological disorders.
     
  6. New drug combination shows promise as powerful treatment for AML
    Researchers identified two drugs that are potent against acute myeloid leukemia (AML) when combined, but only weakly effective when used alone. The study provides a scientific rationale for advancing clinical studies of the drug combination.
     
  7. Biomarker could help diagnose schizophrenia at an early age
    A study described how elevated levels of a protein called CRMP2—found in the brain and blood—could become a format for a rapid, minimally invasive blood test to support the diagnosis of schizophrenia.
     
  8. Scientists identify “immune cop” that detects SARS-CoV-2
    Researchers discovered the sensor in human lungs that detects SARS-CoV-2 and signals that it’s time to mount an antiviral attack. The sensor activates interferon, the body’s own frontline defender against viral invasion.
     
  9. Study finds promising therapeutic target for colitis
    Scientists identified an enzyme in the gut that triggers an inflammatory cascade leading to colitis. Therapeutically targeting the enzyme may be a viable approach to help the millions of people worldwide affected by the disorder.
     
  10. Scientists shrink pancreatic tumors by starving their cellular “neighbors”
    For the first time, blocking “cell drinking,” or micropinocytosis in the thick tissue surrounding a pancreatic tumor, was shown to slow tumor growth—providing more evidence that micropinocytosis is an important therapeutic target.
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This enzyme is one of the hardest working proteins in the body

AuthorMiles Martin
Date

October 21, 2021

Rendering of a red-orange protein molecule on a black background

Researchers from Sanford Burnham Prebys have shown that a protein they identified plays a major role in the breakdown of hyaluronic acid, a compound found in the scaffolding between our cells. The findings, published recently in the Journal of Biological Chemistry, could have implications for epilepsy, cancer and other human diseases associated with hyaluronic acid and similar compounds.

They also shed light on one of the most active biochemical processes in the body. 

“Our body turns over hyaluronic acid at an extremely rapid rate, far faster than the other compounds surrounding our cells,” says senior author Yu Yamaguchi, MD, PhD, a professor in the Human Genetics Program at Sanford Burnham Prebys.

Hyaluronic acid, a common ingredient in cosmetic anti-aging products, is a one of several large sugar molecules known as glycosaminoglycans (GAGs). These are found naturally in the extracellular matrix, the complex network of organic compounds surrounding our cells that gives structure to our tissues. In addition to its structural role, the extracellular matrix is involved in regulating the immune system and is critical in the early development of connective tissues like cartilage, bone and skin.

“The extracellular matrix is found in every organ and tissue of the body, and malfunctions in its biochemistry can trigger or contribute to a variety of diseases, some of which we don’t even know about yet,” says Yamaguchi. His team studies how GAGs affect childhood diseases including congenital deafness, epilepsy and multiple hereditary exostoses, a rare genetic disorder that causes debilitating cartilage growths on the skeleton.

Hyaluronic acid is also known to be correlated with several health conditions, depending on its concentration in certain tissues. Reduced levels of hyaluronic acid in the skin caused by aging contribute to loss of skin elasticity and reduced capacity to heal without scarring. Levels of hyaluronic acid in the blood dramatically increase in alcoholic liver disease, fatty liver and liver fibrosis. In addition, hyaluronic acid levels have been correlated with increased tumor growth in certain cancers.

“These compounds are literally everywhere in the body, and we continue to learn about how GAG’s influence disease, but there’s also a lot we still don’t know about how these molecules are processed,” says Yamaguchi, “Research like this is about understanding what’s happening at the molecular level so we can later translate that into treatments for disease.” 

For this study, the team focused on a protein called TMEM2, which they had previously found to break down hyaluronic acid by cutting the longer molecule into manageable pieces for other enzymes to process further. Using mice as a research model, they selectively shut off the gene that codes for TMEM2 and were able to successfully measure precisely how much the absence of TMEM2 affects the overall levels of hyaluronic acid.

The answer: a lot.

“We saw up to a 40-fold increase in the amount of hyaluronic acid in the study mice compared to our controls,” says Yamaguchi. “This tells us that TMEM2 is one of the key players in the process of degrading this compound, and its dysfunction may be a key player in driving human diseases.” 

The team further confirmed this role of the TMEM2 protein by using fluorescent compounds that detect hyaluronic acid to determine where the TMEM2 protein is most active. They found the most activity on the surface of cells lining blood vessels in the liver and lymph nodes, which are known to be the main sites of hyaluronic acid degradation. 

“These findings refine our understanding of this critical biochemical process and set us up to explore it further in the interest of developing treatments for human diseases,” says Yamaguchi. “Hyaluronic acid is so much a part of our tissues that there could be any number of diseases out there waiting to benefit from discoveries like these.”

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

Authorsgammon
Date

September 22, 2020

DNA illustration

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.

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First supercentenarian-derived stem cells created

AuthorMonica May
Date

March 19, 2020

telomere DNA illustration

Advance primes scientists to unlock the secrets of healthy aging.

People who live more than 110 years, called supercentenarians, are remarkable not only because of their age, but also because of their incredible health. This elite group appears resistant to diseases such as Alzheimer’s, heart disease and cancer that still affect even centenarians. However, we don’t know why some people become supercentenarians and others do not.

Now, for the first time, scientists have reprogrammed cells from a 114-year-old woman into induced pluripotent stem cells (iPSCs). The advance, completed by scientists at Sanford Burnham Prebys and AgeX Therapeutics, a biotechnology company, enables researchers to embark on studies that uncover why supercentenarians live such long and healthy lives. The study was published in Biochemical and Biophysical Research Communications.

“We set out to answer a big question: Can you reprogram cells this old?” says Evan Snyder, MD, PhD, professor and director of the Center for Stem Cells and Regenerative Medicine at Sanford Burnham Prebys, and study author. “Now we have shown it can be done, and we have a valuable tool for finding the genes and other factors that slow down the aging process.”

In the study, the scientists reprogrammed blood cells from three different people—the aforementioned 114-year-old woman, a healthy 43-year-old individual and an 8-year-old child with progeria, a condition that causes rapid aging—into iPSCs. These cells were then transformed into mesenchymal stem cells, a cell type that helps maintain and repair the body’s structural tissues—including bone, cartilage and fat.

The researchers found that supercentenarian cells transformed as easily as the cells from the healthy and progeria samples. As expected, telomeres—protective DNA caps that shrink as we age—were also reset. Remarkably, even the telomeres of the supercentenarian iPSCs were reset to youthful levels, akin to going from age 114 to age zero. However, telomere resetting in supercentenarian iPSCs occurred less frequently compared to other samples—indicating extreme aging may have some lasting effects that need to be overcome for more efficient resetting of cellular aging.

Now that the scientists have overcome a key technological hurdle, studies can begin that determine the “secret sauce” of supercentenarians. For example, comparing muscle cells derived from the healthy iPSCs, supercentenarian iPSCs and progeria iPSCs would reveal genes or molecular processes that are unique to supercentenarians. Drugs could then be developed that either thwart these unique processes or emulate the patterns seen in the supercentenarian cells.

“Why do supercentenarians age so slowly?” says Snyder. “We are now set to answer that question in a way no one has been able to before.”

The senior author of the paper is Dana Larocca, PhD, vice president of Discovery Research at AgeX Therapeutics, a biotechnology company focused on developing therapeutics for human aging and regeneration; and the first author is Jieun Lee, PhD, a scientist at AgeX.

Additional authors include Paola A. Bignone, PhD, of AgeX; L.S. Coles of Gerontology Research Group; and Yang Liu of Sanford Burnham Prebys and LabEaze. The work began at Sanford Burnham Prebys when Larocca, Bignone and Liu were members of the Snyder lab.

The study’s DOI is 10.1016/j.bbrc.2020.02.092.

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10 questions for Alzheimer’s expert Jerold Chun of Sanford Burnham Prebys

AuthorMonica May
Date

September 21, 2019

Jerold Chun, MD PhD

Alzheimer’s is one of the most frightening diseases of our time. Of the top 10 causes of death in the U.S., it is the only disease for which no effective or preventative treatment exists. Recent clinical trial failures have only deepened the pain of patients and their families.

To learn about the state of Alzheimer’s research in the wake of these setbacks—and whether there is hope on the horizon—we caught up with Alzheimer’s expert Jerold Chun, MD, PhD, professor and senior vice president of Neuroscience Drug Discovery at Sanford Burnham Prebys. Chun and his team recently published a Nature study that suggests a potential Alzheimer’s treatment may be closer than we think. 

  1. Why has Alzheimer’s disease become so prevalent? Are we better at diagnosing the disease?
    The number of people with Alzheimer’s disease is rising because of the aging Baby Boomers generation—which makes up more than 20% of the U.S. population. As a result, the number of those living with the condition is projected to more than double by 2050 to nearly 14 million people. This will place an incredible economic and social burden on our society—unless a treatment is found.
     
  2. Are there any treatments that work for Alzheimer’s disease?
    No disease-modifying therapies exist. The medicines a patient can receive today just treat symptoms. For example, cholinesterase inhibitors and N-methyl D-aspartate antagonists treat cognitive symptoms, such as memory loss, confusion and problems with thinking and reasoning—but they aren’t able to stop the disease. 
     
  3. Is it possible to prevent Alzheimer’s?
    Multiple studies from this year’s Alzheimer’s Association International Conference centered on this topic. Evidence suggests that adopting healthy lifestyle choices such as eating a healthy diet, not smoking, exercising regularly and stimulating the mind may decrease the risk of cognitive decline and dementia.

    It is encouraging to know that preventing Alzheimer’s may be partially within our control. However, it is undeniable that even individuals who live a healthy lifestyle will still develop Alzheimer’s. We need to remain laser focused on developing effective preventions and treatments. 
     

  4. Do we know the cause of Alzheimer’s? What are the latest theories?
    In short, no. We know that clumps of amyloid-beta and tau proteins in the brain are linked to the disease. We also know that in rare cases genes are involved, because Alzheimer’s can run in families—but this accounts for less than 1% of cases. New research points to unique gene changes within the brain, called somatic gene recombination, as a new potential factor. Some data also implicate aspects of the immune system. It’s most likely that multiple factors lead to disease—and that an effective treatment will tackle Alzheimer’s from several angles. 
     
  5. How would you describe the pipeline of Alzheimer’s treatments in development?
    The pipeline of Alzheimer’s treatments is in dire need of expansion. As of February 2019, only 132 drugs were under evaluation in clinical trials. Nearly half of these compounds target beta-amyloid. 

    For comparison, there are nearly 4,000 compounds under development for cancer—which affects almost three times as many Americans each year. We certainly need to continue to invest in cancer treatments—but clearly there is an urgent need to fill the Alzheimer’s pipeline, and an even greater need to find an approach that actually works.
     

  6. Tell us more about your research. What did you find? What are the next steps? 
    In school we learned that all cells have the same DNA. However, in our recent research we found that in the brains of patients, the DNA in the Alzheimer’s-linked APP gene can be “mixed and matched” into many different, new forms, some of which aren’t found in healthy individuals. To create these new gene variants, reverse transcriptase—best known as an enzyme infamously used by HIV—is required. This suggests that existing HIV medications—called reverse transcriptase inhibitors—which halt reverse transcriptase, might be useful as a near-term treatment for Alzheimer’s disease. A doctor can prescribe these medicines now as an “off-label” use for the treatment of Alzheimer’s disease. However, prospective clinical trials are needed to test the efficacy and side-effect profiles of these medicines in actual Alzheimer’s disease patients.
     
  7. Are humans the only species that get Alzheimer’s disease? 
    To our knowledge, yes. No other animal has the intellectual and cognitive capacity exhibited by humans. For this reason, scientists have developed animal models that exhibit symptoms and pathologies that approximate the disease.
     
  8. How far away are we from an effective Alzheimer’s treatment? Years or decades? 
    What excites me about my team’s findings is that, if true, a partially effective treatment may be available now. Reverse transcriptase inhibitors are medicines currently used to treat HIV and hepatitis B, and have been safely used for 30 years with millions of patient-years of experience. New medicines based on this approach could lead to next-generation drugs with better efficacy and safety.

    Other agents in the Alzheimer’s pipeline currently in development are many years away from an effective treatment. And, it could take an additional 30 years for such agents to have the same level of proven safety as reverse transcriptase inhibitors. Nevertheless, new therapeutics must be pursued. Hopefully, our adult children will have great medical options in their future.
     

  9. What is the biggest hurdle to developing an Alzheimer’s treatment? 
    A major hurdle is securing funding for early, innovative research. The National Institutes of Health (NIH) is granting more funding than ever before to tackle this disease. However, many people aren’t aware that the NIH overwhelmingly finances projects that are scientifically conservative, which in the case of Alzheimer’s disease has failed to produce effective medicines. Funding that enables scientists to explore new, bold frontiers can be transformational in leading to important advances. This is an area where philanthropic donations can have a major impact—especially now, as the field strives to “think outside of the amyloid box” and explore new approaches.
     
  10.  Are you hopeful for the future? Why or why not?
    I am absolutely hopeful for the future. Advances in fundamental brain science will lead to new treatments for Alzheimer’s disease. Our work will hopefully be a start to a world where our children don’t have to live in fear of this disease.

 

About Jerold Chun 
Jerold Chun, MD, PhD, is a world-renowned neuroscientist who seeks to understand the brain and its diseases. His research has discovered genomic mosaicism and somatic gene recombination, surprising phenomena whereby cells in the brain actually have different genomic DNA sequences that can change with disease states. Chun’s research continues to shed light on Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and other neurodegenerative diseases as well as neuropsychiatric disorders and substance abuse.

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Sanford Burnham Prebys and Salk co-organize third annual La Jolla Aging Meeting

AuthorMonica May
Date

April 11, 2019

Malene Hansen, PhD, and Peter Adams, PhD; and Salk’s Jan Karlseder, PhD

“Excellent presentation!”

“We should connect—we have more samples coming soon.” 

“Feel free to reach out, we’re looking to partner so I’d love to hear more about your research.”

These exchanges, overheard at the 3rd annual La Jolla Aging Meeting held on March 29, 2019, at the Salk Institute, illustrate the importance of uniting scientists focused on a common goal: In this case, uncovering the root causes of aging. 

As in previous years, the 2019 meeting was co-organized by Sanford Burnham Prebys’ Malene Hansen, PhD, and Peter Adams, PhD; and Salk’s Jan Karlseder, PhD A key goal of the event is to feature research by local scientists studying the molecular mechanisms of aging, while fostering connections and building relationships that advance new discoveries. More than 200 researchers, primarily from the San Diego area, attended the meeting. 

La Jolla Aging Meeting tweet​
    For scientists new to the area, the meeting provided a key
    opportunity to build relationships.

Aging is the main risk factor for many of the serious diseases our society faces today, including cancer, heart disease and Alzheimer’s. As the U.S. population grows older due to the natural aging of the Baby-Boomer generation, the need to understand the underlying causes of aging becomes more urgent. The number of Americans who are age 65 or older is projected to double from nearly 48 million in 2015 to more than 90 million in 2060, according to the United States Census Bureau. 

The diversity of presentations given—from the role of supportive brain cells called astrocytes and cellular recycling (autophagy) to long-lived proteins in mitochondria (the cell’s power generator)—reflects the complexity of the field. A poster session was also held during the symposium, providing an opportunity for up-and-coming scientists to share their recent data. 

“It’s unlikely there will be any single factor responsible for aging,” says Matt Kaeberlein, PhD, professor at the University of Washington and the symposium’s keynote speaker. “I am encouraged to see so many people interested in diverse aspects of aging biology at this symposium. By advancing each of these distinct research areas, and working together, we will make progress in understanding the underlying aging process.”

The full list of speakers follows. Make sure to save the date for next year’s meeting, which will be held on March 27, 2020. 

  • Matt Kaeberlein, PhD, University of Washington (keynote) – New insights into mechanisms by which mTOR modulates metabolism, mitochondrial disease and aging
  • Isabel Salas, PhD, Allen lab, Salk – Astrocytes in aging and Alzheimer’s disease
  • David Sala Cano, PhD, Sacco lab, Sanford Burnham Prebys – The Stat3-Fam3a axis regulates skeletal muscle regenerative potential
  • Tina Wang, Ideker lab, University of California, San Diego – A conserved epigenetic progression aligns dog and human age
  • Rigo Cintron-Colon, Conti lab, Scripps Research – Identifying the molecules that regulate temperature during calorie restriction
  • Nan Hao, PhD, University of California, San Diego – Programmed fate bifurcation during cellular aging
  • Shefali Krishna, PhD, Hetzer lab, Salk – Long-lived proteins in the mitochondria and their role in aging
  • Sal Loguercio, PhD, Balch lab, Scripps Research – Tracking aging with spatial profiling
  • Alva Sainz, Shadel lab, Salk – Cytoplasmic mtDNA-mediated inflammatory signaling in cellular aging
  • Anthony Molina, PhD, University of California, San Diego – Mitochondrial bioenergetics and healthy aging: Advancing precision healthcare for older adults
  • Alice Chen, Cravatt lab, Scripps Research – Pharmacological convergence reveals a lipid pathway that regulates C. elegans lifespan
  • Robert Radford, PhD, Karlseder lab, Salk – TIN2: Communicating telomere status to mitochondria in aging
  • Jose Nieto-Torres, PhD, Hansen lab, Sanford Burnham Prebys – Regulating cellular recycling: role of LC3B phosphorylation in vesicle transport

Prizes for the best poster presentations were awarded to the following scientists: 

  • Hsin-Kai Liao, PhD, Juan Carlos Izpisua Belmonte’s lab, Salk  
  • Yongzhi Yang, PhD, Malene Hansen’s lab, Sanford Burnham Prebys
  • Tai Chalamarit, Sandra Encalada’s lab, Scripps Research 

Thank you to our generous sponsor, the Glenn Foundation for Medical Research, and to NanoString for donating the prizes received by the poster presenters.  

Interested in keeping up with our latest discoveries, upcoming events and more? Subscribe to our monthly newsletter, Discoveries.
 

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The slow, silent process of “inflammaging” might kill you

AuthorSusan Gammon
Date

October 5, 2017

Huaxi Xu, PhD

You may recall from biology classes that most DNA is located in the nucleus, the cell’s command center that dictates cell growth, maturation, division and even cell death.  But occasionally, in aging cells that stop growing and dividing (senescent cells), bits of DNA pinch off and accumulate in the cytoplasm.  Although this may seem like an innocent act, cytoplasmic DNA actually triggers an inflammatory path that contributes to many diseases linked with aging.

“We are studying the mechanics of “inflammaging,” says Peter Adams, PhD, professor at SBP.  “The term refers to the pervasive, chronic inflammation that occurs in aging tissue. Understanding how inflammation occurs in aging tissue opens new avenues to treat a variety of age-related diseases such as rheumatoid arthritis, liver disease, atherosclerosis, muscle wasting (sarcopenia), and even cancer.”

Adams’ most recent study, a collaboration with Shelley Berger, PhD, professor at University of Pennsylvania, studied senescent cells to figure out how cytoplasmic DNA activates inflammation.  Senescent cells can be long-lived and accumulate in aged and damaged organs, attracting inflammatory cells that promote tissue damage.

Their new research, published in Nature, is the first to describe how in senescent cells, cytoplasmic DNA fragments activate the cGAS-STING pathway, a component of the immune system that leads to the secretion of pro-inflammatory cytokines.  

“Pro-inflammatory cytokines, such as interferon and tumor necrosis factor (TNF) promote inflammation, which can be a good thing when you need it,” explains Adams.  “Acute inflammation, for example, is a natural, healthy process that attracts and activates immune cells to heal wounds and fight infections.  And in the right circumstances, when our immune system recognizes cancer cells as foreign, these cytokines can activate powerful anti-tumor immune responses.

“But chronic, uncontrolled inflammation is a potentially harmful process.  It can lead to the destruction of tissue, and a list of diseases that range from skin conditions like psoriasis to deadly liver cancer.  So the inflammatory process must be tightly regulated to avoid excessive tissue damage and spillover to normal tissue—and these risks increase with age.

“Now that we understand how cytoplasmic DNA leads to chronic inflammation in senescent cells—through the cGAS-STING pathway—we have the opportunity to think about therapeutic strategies to intervene to delay or prevent “inflammaging” related diseases.

DOI: 10.1038/nature24050

Related: Cancer biology: Genome jail-break triggers lockdown (Nature Magazine)

 

 

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Slowing down the “aging clock”

AuthorJessica Moore
Date

April 14, 2017

old man walking across clock

What if it were possible to slow down the clock on aging? There may indeed be such a clock in all your cells. New research from the laboratory of Peter Adams, PhD, professor at Sanford Burnham Prebys Medical Discovery Institute (SBP), provides further evidence that the epigenome—the pattern of chemical tags across our chromosomes that help determine which genes can be read—is the key to aging.

“We found that conditions or treatments that extend lifespan make the epigenome of an old animal look like that of a much younger one,” says Adams, senior author of one of a pair of studies in Genome Biology. “In other words, the ‘epigenetic clock’ can be slowed. That suggests that to help people stay healthy longer and lower their risk of diseases like Alzheimer’s, cancer, and atherosclerosis, we should find molecules that do the same thing.”

Adams’ studies, performed in collaboration with the lab of Trey Ideker, PhD, professor at UC San Diego, build on previous findings in humans. Ideker and subsequently other teams of scientists had identified the genomic sites at which the presence or absence of a chemical tag correlates with age, and created an algorithm to tell a person’s age within two or three years by analyzing all those sites. This epigenetic clock speeds up in people with diseases that lead to earlier onset of aging-associated problems, such as obesity or HIV infection, or who have survived severe psychological stress in childhood.

Adams’ and Ideker’s teams showed that longevity-conferring interventions have the opposite effect—they put a brake on age-associated epigenetic changes. To make that discovery, they compared the epigenomes of normal mice to those of mice in which aging was slowed by three strategies that are all well known to extend the mouse lifespan: a longevity mutation (Prop1df/df, which also causes dwarfism), caloric restriction (reducing dietary intake significantly, but not enough to harm the mice), and rapamycin, a drug with multiple effects on metabolism and the immune system.

“To show that longer life correlates with slower epigenetic aging, we first had to delineate the mouse epigenetic clock,” adds Adams. “That provides us with a very useful tool. Now we can do experiments to find out whether epigenetic changes actually drive aging. For example, we can compare animals with slow and fast epigenetic clocks to see if the ones that age slower stay healthier as they age.

“And we can investigate how the epigenetic clock “ticks”—what cellular processes cause these changes over time? The answers to that question could identify targets for anti-aging medicines.”

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An “Odd” gene affects aging of the heart

AuthorJessica Moore
Date

February 1, 2017

hands holding heart

As we get older, our hearts change in ways that make it harder for them to pump blood. They become stiffer, less efficient at generating energy, and more likely to respond to damage with inflammatory chemicals. To help find new ways to slow that decline, researchers in the laboratory of Rolf Bodmer, PhD, professor and director of the Development, Aging and Regeneration Program at Sanford Burnham Prebys Medical Discovery Institute (SBP), are looking at how the heart ages at a molecular level.

Bodmer’s team recently discovered a new potential contributor to cardiac aging, a protein called Odd, opening up a novel direction for research on therapies to prolong heart health. In their study, published in the journal Aging Cell, the gene for Odd, which controls the activity of other genes by turning them on or off, was found to be turned up in the hearts of old fruit flies. Bodmer’s lab studies flies because their hearts deteriorate with age in the same ways that human hearts do, but their genetics are much simpler.

“It’s intriguing that Odd is linked to aging because its known function is in early development—it’s crucial for the heart to form properly, and, as we found here, is also important for preventing the heart from deteriorating prematurely,” says Bodmer.

Odd’s involvement in cardiac aging was uncovered by a genome-wide comparison of the genes that are active in the hearts of young and old flies. Odd was one of over 200 genes whose activity was significantly elevated in older flies. Remarkably, further analysis showed that in aging hearts, increasing Odd activity temporarily protects the heart from decline by supporting proper electrical function and heart rate.

“Our findings suggest that increased levels of Odd in older hearts may be a way to compensate for aging-associated loss of function,” comments Bodmer. “In combination with a companion paper showing that another gene-regulating protein, FoxO, helps preserve the adult heart, they support a growing body of evidence that genes that are crucial in development are also important to keep the heart running well into old age.”

Bodmer contributed to the other paper, from the lab of Anthony Cammarato, PhD, assistant professor at Johns Hopkins University School of Medicine, and previously a staff scientist in Bodmer’s lab. The paper showed that FoxO helps protect the aging heart by turning on genes that help get rid of unneeded proteins.

“Following up on the findings of both studies could point to ways to keep our hearts working better for longer,” Bodmer adds.

The Bodmer lab paper is available online here and the Cammarato lab paper is here.

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Siobhan Malany, PhD, selected to conduct novel medical research in space

AuthorDeborah Robison
Date

June 13, 2016

ISS from space

Siobhan Malany, PhD, director of Translational Biology at Sanford Burnham Prebys Medical Discovery Institute at Lake Nona (SBP) and founder of the Institute’s first spin-off company, Micro-gRx, Inc., has been awarded $435,000 to study atrophy in muscle cells in microgravity on the International Space Station (ISS). In microgravity, conditions accelerate changes in cell growth similar to what occurs in the aging and disease process of tissues. Using real-time analysis, Malany will be able to rapidly study cells for potential new therapeutic approaches to muscle degeneration associated with aging, injury or illness. Continue reading “Siobhan Malany, PhD, selected to conduct novel medical research in space”