Nav: Home

A deep dive into cellular aging

February 20, 2020

LA JOLLA, CALIF. - Feb. 20, 2020 - Scientists at Sanford Burnham Prebys Medical Discovery Institute and Harvard University have discovered that mitochondria trigger senescence, the sleep-like state of aged cells, through communication with the cell's nucleus--and identified an FDA-approved drug that helped suppress the damaging effects of the condition in cells and mice. The discovery, published in Genes & Development, could lead to treatments that promote healthy aging or prevent age-associated diseases such as cancer, Alzheimer's disease, heart disease and more.

"Our findings provide a foundation upon which we can start to develop drugs that extend our health span--the number of years we live a healthy life," says Peter Adams, Ph.D., a professor in Sanford Burnham Prebys' National Cancer Institute (NCI)-designated Cancer Center and senior author of the study. "Given the major social and economic hurdles we will soon face as millions of Americans grow older, interventions can't come soon enough."

The number of Americans who are age 65 or older is projected to double to more than 90 million in 2060, translating to nearly 25% of the population, due to the natural aging of the Baby Boomer generation. Today, approximately 80% of older adults have at least two chronic diseases, such as heart disease, cancer, stroke or diabetes. This trend creates a need to solve the projected onslaught of health problems we face and is fueling scientists to dive into the molecular causes of aging and find medicines that help people live long, healthy lives.

"To cope with the rise of chronic diseases from an aging population, we must understand the fundamental biological effects of aging," says Mark R. Collins, president and director of the Glenn Foundation, which partially funded the research. "These findings provide insights that bring us closer to treatment(s) that could prevent or delay the onset of many age-related diseases."

Connecting the dots

For more than a decade, Adams has studied how clusters of chromatin--the mix of DNA and protein normally found in the cell nucleus--leak out to the cytoplasm in senescent cells, triggering inflammatory signals that can promote a number of undesirable health conditions. In this study, his team set out to find what prompts the formation of chromatin clusters in the first place.

To answer this question, the scientists embarked on a series of experiments using a human lung cell model of senescence. They found that mitochondria were the culprits driving the formation of pro-inflammatory cytoplastic chromatin and did so through a retrograde communication path to the nucleus.

"In school we learned that the role of mitochondria is to generate energy--and that DNA controls everything the cell does," says Adams. "Research is now showing that mitochondria are important sensors for the cell and have a lot of cross-talk with the nucleus, which makes sense given their duty to respond to the cell's metabolic needs."

The scientists also found that an HDAC inhibitor, an FDA-approved drug currently used to treat certain cancers, transformed senescent cells from a large and flat form to a healthier and more visually youthful condition. The HDAC inhibitor-treated cells also had better mitochondrial function, less cytoplasmic chromatin and produced less inflammatory signals. The scientists observed similar beneficial effects when examining the livers of mice in which senescence was induced through radiation or high doses of acetaminophen. However, the side effects of HDAC inhibitors--which include fatigue, nausea and more--make the drugs too toxic for use in preventing disease in healthy individuals.

As a next step, the scientists hope to screen for less toxic senescence-inhibiting drugs at the Institute's Conrad Prebys Center for Chemical Genomics. For example, a compound that interrupts the communication between the mitochondria and the nucleus would hold promise as a treatment that promotes healthy aging.

"This study provides the first concrete link between several known hallmarks of aging--dysfunctional mitochondria, inflammation and senescent cells--which historically were studied as separate events," says Adams. "We are hopeful that targeting the molecular drivers of senescence will lead us to safe and effective medicines that help more people stay as healthy as possible, for as long as possible."
-end-
The first author of the study is Maria Grazia Vizioli of Cancer Research UK, University of Glasgow and Harvard University. Additional study authors include Tianhui Liu and Karl N. Miller, who contributed equally to the study; Nirmalya Dasgupta and Xue Lei of Sanford Burnham Prebys; Neil Robertson, Kathryn Gilroy, Arantxa Perez-Garcia and Christos Kiourtis of Cancer Research UK and University of Glasgow; Patrick J. Kruger and Anthony Lagnado of the Mayo Clinic; Colin Nixon and William Clark of Cancer Research UK; Diana Jurk and João F. Passo of Mayo Clinic and Newcastle University; Shelley L. Berger of University of Pennsylvania; Thomas G. Bird of Cancer Research UK and University of Edinburgh; and Zhixun Dou of Harvard University and co-corresponding author.

The study's DOI is 10.1101/gad.331272.119.

Research reported in this press release was supported by the National Institutes of Health (NIH) (P01AG03186211, F32AG066459, K99AG053406 and P01AG03186211); the Glenn Foundation for Medical Research (PD18082 and PD19131); the Ted Nash Foundation; CRUK Beatson Institute (A171196) and the Wellcome Trust (WT107492Z).

About Sanford Burnham Prebys Medical Research Institute

Sanford Burnham Prebys is a preeminent, independent biomedical research institute dedicated to understanding human biology and disease and advancing scientific discoveries to profoundly impact human health. For more than 40 years, our research has produced breakthroughs in cancer, neuroscience, immunology and children's diseases, and is anchored by our NCI-designated Cancer Center and advanced drug discovery capabilities. For more information, visit us at SBPdiscovery.org or on Facebook at facebook.com/SBPdiscovery and on Twitter @SBPdiscovery.

Sanford Burnham Prebys Medical Discovery Institute

Related Cancer Articles:

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
More Cancer News and Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Clint Smith
The killing of George Floyd by a police officer has sparked massive protests nationwide. This hour, writer and scholar Clint Smith reflects on this moment, through conversation, letters, and poetry.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.