Link between cells associated with aging and bone loss

August 21, 2017, Mayo Clinic
Osteoblasts actively synthesizing osteoid. Credit: Robert M. Hunt; Wikipedia.

Mayo Clinic researchers have reported a causal link between senescent cells - the cells associated with aging and age-related disease - and bone loss in mice. Targeting these cells led to an increase in bone mass and strength. The findings appear online in Nature Medicine.

Low bone mass and osteoporosis are estimated to be a major public health threat for almost 44 million U.S. women and men 50 and older, according to the National Osteoporosis Foundation. Bone is a living tissue that is constantly being broken down and replaced. Osteoporosis occurs when the creation of new bone doesn't keep up with the removal of old bone.

"While we know from previous work that the accumulation of senescent cells causes tissue dysfunction, the role of cell senescence in osteoporosis up to this point has been unclear," says Sundeep Khosla, M.D., director of the Aging Bone and Muscle program at Mayo Clinic's Robert and Arlene Kogod Center on Aging. "The novelty of this work for the bone field lies in the fact that, rather than targeting a bone-specific pathway, as is the case for all current treatments for osteoporosis, we targeted a fundamental aging process that has the potential to improve not only bone mass, but also alleviate other age-related conditions as a group."

In the study, researchers used multiple approaches to target senescent cells in mice with established bone loss between 20 and 22 months of age. That's the equivalent of over age 70 in humans. Approaches included using:

  • A genetic model where senescent cells can be killed off
  • A pharmacological approach, where senolytic drugs previously developed at Mayo Clinic eliminate senescent cells
  • A Janus kinase inhibitor - a that blocks the activity of Janus kinase enzymes - to eliminate the toxic products produced by senescent cells

"The effects of all three approaches on aging bone were strikingly similar," says Dr. Khosla. "They all enhanced and strength by reducing but maintaining or increasing bone formation, which is fundamentally different from all current osteoporosis drugs."

The benefits on bone found in elderly mice were not evident in younger mice. That, coupled with the finding that the senolytic drugs were effective when given only intermittently, supports the link between senescent cells and age-related bone loss. Researchers administered a senolytic drug combination (dasatinib and quercetin) once per month to eliminate cells.

"Even though this senolytic drug combination was only present in the mice for a couple of hours, it eliminated and had a long-lasting effect," says James Kirkland, M.D., Ph.D., director of the Kogod Center on Aging and co-corresponding author of the study. "This is another piece of the mounting evidence that senolytic drugs are targeting basic aging processes and could have widespread application in treating multiple chronic diseases."

Drs. Kirkland and Khosla say that being able to administer the drugs intermittently poses less risk for side effects than with drugs that must be taken daily. Also, current therapeutics in the bone field that treat "work against themselves," meaning that, if they decrease resorption, they also decrease formation. In this study, the senolytic drugs decreased bone resorption, while maintaining or increasing .

"With the aging of the population in the U.S. and around the world, age-related loss is going to continue to be an enormous public health problem, and patients with osteoporosis have a higher risk for other age-related comorbidities," says Dr. Khosla. "By combining the knowledge of three separate labs and enlisting the expertise of several others in a true team science approach, we were able to collaborate and make these findings possible. We need to continue to pursue these potential interventions that target fundamental aging mechanisms as, hopefully, an eventual way to reduce the burden of fractures and other conditions, such as cardiovascular dysfunction, diabetes and frailty."

Explore further: Researchers uncover new agents

More information: Targeting cellular senescence prevents age-related bone loss in mice, Nature Medicine (2017). DOI: 10.1038/nm.4385

Related Stories

Researchers uncover new agents

March 9, 2017
Mayo Clinic researchers have uncovered three new agents to add to the emerging repertoire of drugs that aim to delay the onset of aging by targeting senescent cells - cells that contribute to frailty and other age-related ...

Weight loss surgery's effects on bone marrow fat and bone mass

August 9, 2017
Bone marrow fat is thought to regulate bone metabolism, and high levels of marrow fat are seen in states of low bone mass, severe underweight, and diabetes. In a study of obese women undergoing gastric bypass surgery, increases ...

A closer look at osteoporosis medication's mechanisms may improve outcomes

July 31, 2017
Osteoporosis is the primary cause of bone fractures in the elderly. Bone loss in this disease reflects an imbalance between the activity of bone-degrading cells called osteoclasts and bone-building cells called osteoblasts. ...

Long-term benefits of 'senolytic' drugs on vascular health in mice

February 11, 2016
Building on previous studies, Mayo Clinic researchers have demonstrated significant health improvements in the vascular system of mice following repeated treatments to remove senescent cells. They say this is the first study ...

Researchers discover gene that slows bone loss and promotes bone formation

August 12, 2014
(Medical Xpress)—Osteoporosis and aging-related bone loss is debilitating and painful. With a greater understanding of Wnt4 signaling, researchers are now closer to developing therapeutic agents that could slow down bone ...

Researchers reduce stem cell dysfunction and metabolic disease in aged mice

January 4, 2016
Mayo Clinic researchers have taken what they hope will be the first step toward preventing and reversing age-related stem cell dysfunction and metabolic disease. That includes diabetes, which affects 12.2 million Americans ...

Recommended for you

Deep space radiation treatment reboots brain's immune system

May 21, 2018
Planning a trip to Mars? You'll want to remember your anti-radiation pills.

Receptor proteins that respond to nicotine may help fat cells burn energy

May 21, 2018
The same proteins that moderate nicotine dependence in the brain may be involved in regulating metabolism by acting directly on certain types of fat cells, new research from the University of Michigan Life Sciences Institute ...

Atomic-level study reveals why rare disorder causes sudden paralysis

May 21, 2018
A rare genetic disorder in which people are suddenly overcome with profound muscle weakness is caused by a hole in a membrane protein that allows sodium ions to leak across cell membranes, researchers at the University of ...

New era for blood transfusions through genome sequencing

May 18, 2018
Most people are familiar with A, B, AB and O blood types, but there are hundreds of additional blood group "antigens" on red blood cells—substances that can trigger the body's immune response—that differ from person to ...

Robots grow mini-organs from human stem cells

May 17, 2018
An automated system that uses robots has been designed to rapidly produce human mini-organs derived from stem cells. Researchers at the University of Washington School of Medicine in Seattle developed the new system.

Scientists uncover a new face of a famous protein, SWI2/SNF2 ATPase

May 17, 2018
A team of Texas A&M and Texas A&M AgriLife Research scientists now have a deeper understanding of a large switch/sucrose non-fermentable (SWI/SNF) protein complex that plays a pivotal role in plant and human gene expression ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.