Breaking News
July 17, 2018 - White adolescent boys experiencing early puberty have high risk for substance use
July 17, 2018 - Celgene and Acceleron Announce Luspatercept Achieved Primary and All Key Secondary Endpoints in Phase III ‘BELIEVE’ Study in Adults with Transfusion-Dependent Beta-Thalassemia
July 17, 2018 - Roots of leukemia reveal possibility of predicting people at risk
July 17, 2018 - Summer med program embraces low-income students’ potential
July 17, 2018 - New research lays foundation to create standards for RNA sequencing
July 17, 2018 - CRISPR/Cas9 gene editing can cause greater genetic damage than previously thought
July 17, 2018 - Democrats rally against threats to the ACA to block Trump’s Supreme Court nominee
July 17, 2018 - Staggering prices slow insurers’ coverage of CAR-T cancer therapy
July 17, 2018 - How proteins involved in neurodegeneration enter cells
July 17, 2018 - New super-resolution ‘nanoscope’ provides insight into progression of Alzheimer’s disease
July 17, 2018 - FDA Advisory Committee Endorses the Effectiveness and Safety of Single-Dose Tafenoquine for the Radical Cure of P. vivax Malaria
July 17, 2018 - Uncovering the evolutionary history of IBD-associated colorectal cancer
July 17, 2018 - Is nutrition research dependable? Stanford’s John Ioannidis weighs in
July 17, 2018 - New machine learning framework predicts effects of genetic mutations in ‘dark matter’ regions
July 17, 2018 - Plant-based products fail to have positive impact on blood pressure during clinical studies
July 17, 2018 - Electronic system to speed up facial pain diagnosis may improve quality of life and save money
July 17, 2018 - Study delves into the role played by Protein Kinase C in synaptic plasticity
July 17, 2018 - Women Often Unaware of Their Hospital’s Religious Affiliation
July 17, 2018 - New AASM guideline recommends use of actigraphy for sleep disorders
July 17, 2018 - CRISPR editing reduces repetitive behavior in mice with a form of autism
July 17, 2018 - Scientists use magnets to detect cancer
July 17, 2018 - Microfluidic chip to detect sepsis proves successful in clinical study
July 17, 2018 - Research provides better understanding of mechanisms underlying memory storage
July 17, 2018 - A Multi-Modal Approach for the Early Detection of Breast Cancer
July 17, 2018 - Mailing colorectal cancer tests to patients increases screening rates, report researchers
July 17, 2018 - Scientists find possible sources of medicinal and antimicrobial drugs
July 17, 2018 - Molecules formed when the body metabolizes omega-3 fatty acids may inhibit cancer
July 17, 2018 - Efficient communication between hospitals improves patient safety and reduces mortality
July 17, 2018 - Study highlights potential of fetal gene therapy to prevent lethal neurodegenerative disease
July 17, 2018 - For Americans, in Science They Trust
July 17, 2018 - Combating HIV/AIDS | NIH MedlinePlus the Magazine
July 17, 2018 - Study shows minorities widely underrepresented in autism diagnoses
July 17, 2018 - Multigene testing replacing BRCA tests for breast cancer risk | News Center
July 17, 2018 - Pre-clinical pilot study shows promising results of ‘concussion pill’
July 17, 2018 - Researchers reduce size of tumors in mice by artificially activating the brain’s reward system
July 17, 2018 - New study documents symptoms of people before they acquire multiple sclerosis
July 17, 2018 - Researchers discover why CRISPR gene editing sometimes fails
July 17, 2018 - New finding may hold key to better understand the complexities of neurological disorders
July 17, 2018 - The Current issue of “The view from here” is concerned with Novel Targets.
July 17, 2018 - Fighting the Flu with a Universal Vaccine
July 17, 2018 - Key social reward circuit in the brain impaired in kids with autism | News Center
July 17, 2018 - Insight into causes, types and treatment of aphasia
July 16, 2018 - Quark Pharmaceuticals, Inc Announces First Patient Dosed in Phase 3 Clinical Trial of QPI-1002 for Prevention of Acute Kidney Injury Following Cardiac Surgery
July 16, 2018 - NSAIDs shown to have causal role in cardiovascular risk of patients with osteoarthritis
July 16, 2018 - PET scan tracer predicts success of cancer ‘vaccine’ | News Center
July 16, 2018 - Parents struggle with what to do when their child has headache, shows study
July 16, 2018 - Outrageous or overblown? HHS announces another round of ACA navigator funding cuts
July 16, 2018 - Weight loss surgery may impact individual’s risk of developing cancer, shows study
July 16, 2018 - Alexion Submits Application for Priority Review and Approval of ALXN1210 as a Treatment for Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) in the U.S.
July 16, 2018 - Restoring epigenetic balance reinstates memory in flies with Alzheimer’s disease symptoms
July 16, 2018 - Magnetized wire could be used to detect cancer in people | News Center
July 16, 2018 - Non-surgical management found to be feasible option for penetrating kidney trauma
July 16, 2018 - California clinic screens asylum seekers for honesty
July 16, 2018 - FDA Approves Xtandi (enzalutamide) for the Treatment of Men with Non-Metastatic Castration-Resistant Prostate Cancer (CRPC)
July 16, 2018 - Can nanotechnology help treat Alzheimer’s?
July 16, 2018 - Researchers identify protein essential for making stem cells | News Center
July 16, 2018 - Severe childhood infections linked with lower school achievement in adolescence
July 16, 2018 - Radiologist discusses causes, treatments of varicose veins
July 16, 2018 - Researchers develop nanostructured surface to accelerate wound healing after dental implants
July 16, 2018 - New non-invasive procedure to reposition kidney stones could benefit astronauts
July 16, 2018 - Attending Surgeon Influences Genetic Testing in Breast Cancer
July 16, 2018 - Medical doctors with addictions fear professional repercussions if they seek treatment
July 16, 2018 - 5 Questions: John Ioannidis calls for more rigorous nutrition research | News Center
July 16, 2018 - University of Illinois buys 3D-Bioplotter for regenerative biology, tissue engineering research
July 16, 2018 - Charité’s researchers integrate open-source platform into the ‘Human Brain Project’
July 16, 2018 - SUSU scientists develop rehabilitation device for people with lower limbs injuries
July 16, 2018 - Researchers find definite increase in scooter-related injuries
July 16, 2018 - Researchers solve mystery of final blood group system
July 16, 2018 - Researchers develop near-infrared fluorophores-based PDT to cure cancer with less side effects
July 16, 2018 - Traumatic brain injury biomarker could help predict patient prognosis
July 16, 2018 - Researchers to investigate role of hormones in mosquito’s ability to use human blood for egg production
July 16, 2018 - AHA: Doctor Makes Lifesaving House Call in His Own Home
July 16, 2018 - Nearsightedness – Genetics Home Reference
July 16, 2018 - Study shows biomarker panel boosts lung cancer risk assessment for smokers
July 16, 2018 - Researchers find link between bereavement during pregnancy, child’s mental health | News Center
July 16, 2018 - Legalizing same-sex marriage has meaningful effects on health care access for sexual-minority men
July 16, 2018 - New York to allow medical marijuana as substitute to opioids
July 16, 2018 - Reducing tapeworm infection could improve academic performance, reduce poverty | News Center
July 16, 2018 - Researchers describe key role of enzyme in regulating immune response against Chagas disease parasite
July 16, 2018 - Johnson & Johnson Announces Publication in The Lancet Highlighting Robust Immune Response to Janssen’s Mosaic-based Preventive Vaccine Regimen for HIV
Senolytic drugs reverse damage caused by senescent cells in mice

Senolytic drugs reverse damage caused by senescent cells in mice

image_pdfDownload PDFimage_print

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.


Explore further:
Researchers uncover new agents

More information:
Senolytics improve physical function and increase lifespan in old age, Nature Medicine (2018). DOI: 10.1038/s41591-018-0092-9 , https://www.nature.com/articles/s41591-018-0092-9

Journal reference:
Nature Medicine

Provided by:
National Institutes of Health

Tagged with:

About author

Related Articles