Nav: Home

Senolytic drugs reverse damage caused by senescent cells in mice

July 09, 2018

Injecting senescent cells into young mice results in a loss of health and function but treating the mice with a combination of two existing drugs cleared the senescent cells from tissues and restored physical function. The drugs also extended both life span and health span in naturally aging mice, according to a new study in Nature Medicine, published on July 9, 2018. The research was supported primarily by the National Institute on Aging (NIA), part of the National Institutes of Health (NIH).

A research team led by James L. Kirkland, M.D., Ph.D., of the Mayo Clinic in Rochester, Minnesota, found that injecting even a small number of senescent cells into young, healthy mice causes damage that can result in physical dysfunction. The researchers also found that treatment with a combination of dasatinib and quercetin could prevent cell damage, delay physical dysfunction, and, when used in naturally aging mice, extend their life span.

"This study provides compelling evidence that targeting a fundamental aging process--in this case, cell senescence in mice--can delay age-related conditions, resulting in better health and longer life," said NIA Director Richard J. Hodes, M.D. "This study also shows the value of investigating biological mechanisms which may lead to better understanding of the aging process."

Many normal cells continuously grow, die, and replicate. Cell senescence is a process in which cells lose function, including the ability to divide and replicate, but are resistant to cell death. Such cells have been shown to affect neighboring ones because they secrete several pro-inflammatory and tissue remodeling molecules. Senescent cells increase in many tissues with aging; they also occur in organs associated with many chronic diseases and after radiation or chemotherapy.

Senolytics are a class of drugs that selectively eliminate senescent cells. In this study, Kirkland's team used a combination of dasatinib and quercetin (D+Q) to test whether this senolytic combination could slow physical dysfunction caused by senescent cells. Dasatinib is used to treat some forms of leukemia; quercetin is a plant flavanol found in some fruits and vegetables.

To determine whether senescent cells caused physical dysfunction, the researchers first injected young (four-month-old) mice with either senescent (SEN) cells or non-senescent control (CON) cells. As early as two weeks after transplantation, the SEN mice showed impaired physical function as determined by maximum walking speed, muscle strength, physical endurance, daily activity, food intake, and body weight. In addition, the researchers saw increased numbers of senescent cells, beyond what was injected, suggesting a propagation of the senescence effect into neighboring cells.

To then analyze whether a senolytic compound could stop or delay physical dysfunction, researchers treated both SEN and CON mice for three days with the D+Q compound mix. They found that D+Q selectively killed senescent cells and slowed the deterioration in walking speed, endurance, and grip strength in the SEN mice.

In addition to young mice injected with senescent cells, the researchers also tested older (20-month-old), non-transplanted mice with D+Q intermittently for 4 months. D+Q alleviated normal age-related physical dysfunction, resulting in higher walking speed, treadmill endurance, grip strength, and daily activity.

Finally, the researchers found that treating very old (24- to 27-month-old) mice with D+Q biweekly led to a 36 percent higher average post-treatment life span and lower mortality hazard than control mice. This indicates that senolytics can reduce risk of death in old mice.

"This is exciting research," said Felipe Sierra, Ph.D., director of NIA's Division of Aging Biology. "This study clearly demonstrates that senolytics can relieve physical dysfunction in mice. Additional research will be necessary to determine if compounds, like the one used in this study, are safe and effective in clinical trials with people."

The researchers noted that current and future preclinical studies may show that senolytics could be used to enhance life span not only in older people, but also in cancer survivors treated with senescence-inducing radiation or chemotherapy and people with a range of senescence-associated chronic diseases.
-end-
This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process--each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.

About the National Institute on Aging: The NIA leads the federal government effort conducting and supporting research on aging and the health and well-being of older people. The Institute's broad scientific program seeks to understand the nature of aging and to extend the healthy, active years of life. For more information on research, aging, and health, go to http://www.nia.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIH...Turning Discovery into Health

NIH/National Institute on Aging

Related Aging Articles:

Brain development and aging
The brain is a complex organ -- a network of nerve cells, or neurons, producing thought, memory, action, and feeling.
Aging gracefully in the rainforest
In an article that appears in the current issue of Evolutionary Anthropology, researchers synthesize over 15 years of theoretical and empirical findings from long-term study of the Tsimane forager-farmers.
Reversing aging now possible!
DGIST's research team identified the mechanism of reversible recovery of aging cells by inducing lysosomal activation.
Brain-aging gene discovered
Researchers at Columbia University Medical Center have discovered a common genetic variant that greatly affects normal brain aging in older adults.
Aging can be good for you (if you're a yeast)
It's a cheering thought for anyone heading towards their golden years.
How eating less can slow the aging process
New research shows why calorie restriction made mice live longer and healthier lives.
Turning back the aging clock
By boosting genes that destroy defective mitochondrial DNA, researchers can slow down and potentially reverse an important part of the aging process.
Insilico Medicine launches a deep learned biomarker of aging, Aging.AI 2.0 for testing
Insilico Medicine, Inc., a company applying latest advances in deep learning to biomarker development, drug discovery and aging research, launched Aging.AI 2.0.
Substance with the potential to postpone aging
The coenzyme NAD+ plays a main role in aging processes.
What does a healthy aging cat look like?
Just as improved diet and medical care have resulted in increased life expectancy in humans, advances in nutrition and veterinary care have increased the life span of pet cats.

Related Aging Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...