NIH-funded researchers see extended health span and life span in treated mice
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.
The Latest on: Senolytics
via Google News
The Latest on: Senolytics
- Anti-aging senolytics drugs found to improve mice health and lifespanon July 11, 2019 at 5:00 pm
Researchers have found more evidence that a new class of drugs called senolytics can help fight the physical signs of aging(Credit: ia__64/Depositphotos) Short of stumbling onto a genie or the ...
- Senolytics Show Promise Against Alzheimer’s in Miceon April 15, 2019 at 7:09 am
For the past quarter century, scientists battled Alzheimer’s disease under a single guiding principle: that protein clumps—beta-amyloid—deposited outside sensitive brain cells gradually damage ...
- Plaques Age Glial Precursors, Stoking Inflammationon April 11, 2019 at 8:26 am
Drugs that clear senescent cells—known as senolytics—eliminated senescent OPCs and reduced neuroinflammation, microgliosis, and Aβ load in transgenic mouse models of AD, all the while improving their ...
- Health New drug could mean a longer, healthier lifeon April 7, 2019 at 8:03 pm
Scientists at the Robert and Arlene Kogod Center on Aging at the Mayo Clinic in Minnesota have started trialling “senolytics”, drugs that seem to be slowing down or maybe even reversing the ageing ...
- Senolytics: A new class of drugs with the potential to slow the aging processon March 9, 2019 at 4:00 pm
It is hope a new class of drugs found to slow the aging process in mice could have the same effects in humans (Photo: Shutterstock) It's a cruel irony that when we're young we want to be older, but ...
- A cell-killing strategy to slow aging passed its first test this yearon February 13, 2019 at 3:00 am
The small study in people with lung disease, reported in January, is being billed as the first attempt at “senolytics,” or employing drugs to clear people’s bodies of aged, toxic cells. Some ...
- How Genome Sequencing and Senolytics Can Help Us Live Healthier, Longeron February 1, 2019 at 7:08 am
The causes of aging are extremely complex and unclear. With the dramatic demonetization of genome reading and editing over the past decade, and Big Pharma, startups, and the FDA starting to face aging ...
- First-in-human trial of senolytic drugs encouragingon January 7, 2019 at 8:49 am
Researchers publish the first data on the treatment of an age-related disease with drugs called senolytics. The results in patients with deadly idiopathic pulmonary fibrosis are encouraging and ...
- When Is The Quest For Anti-Aging Going Too Far?on December 27, 2018 at 10:46 pm
With all the breakthroughs, new drugs being developed, stem cells, senolytics, and the elixir of youth seeming to be appearing on the horizon, is there a need to draw the line, and if so when?
via Bing News