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Senolytic Drugs May Reverse Damage Caused By Senescent Cells

5 years, 10 months ago

12602  0
Posted on Aug 30, 2018, 7 p.m.

Injecting senescent cells into young mice resulted in loss of health and function, treating mice with combination of 2 existing drugs cleared senescent cells from tissues, restored physical function, extended lifespan and healthspan in naturally again mice, as published in Nature Medicine.

Injecting even small numbers of senescent cells into you healthy mice has been found to cause damage resulting in physical damage, treatment with combination of dasatinib and quercetin prevented damage, delayed physical dysfunction, and when used in naturally again mice extended lifespan, according to the researchers.

Researchers suggest compelling evidence has been been provided showing that targeting a fundamental ageing process such as cell senescence can delay age related conditions resulting in better health and longer life; and value of investigating biological mechanisms that may lead to better understandings of the ageing process.

Most normal cells grow, die, and replicate continuously; cell senescence is the process in which cells lose function including ability to divide and replicate but are resistant to death which have been shown to affect neighboring cells as they secrete pro-inflammatory and tissue remodeling molecules. With ageing senescent cell numbers increase in many tissues, and they also occur in organs associated with most chronic diseases and chemotherapy/radiation.

Senescent cells can be selectively eliminated with senolytic classes of drugs. In this study dasatinib and quercetin combination was used to test whether they could slow physical dysfunction caused by senescent cells. To determine whether such cells caused physical dysfunction young mice were injected with SEN cells on Con cells. 2 weeks after transplant SEN mice showed impaired physical function as determined by food intake, daily activity, muscle strength, walking speed, body weight, and physical endurance; increased numbers of senescent cells were observed beyond what was injected suggesting propagation of senescence effect into neighboring cells.

To analyze whether senolytic compounds could stop or delay physical dysfunction both mice groups were treated with the dasatinib and quercetin combination; it was found that the mixture selectively killed senescent cells and slowed deterioration in endurance, grip strength, and walking speed in SEN mice.

Older non transplanted mice were treated with the mixture intermittently for 4 months which was found to alleviate normal age related physical dysfunction resulting in higher walking speeds, treadmill endurance, grip strength, and daily activity. Very old mice treated with the compound biweekly led to 36% higher average post treatment lifespan and lower mortality hazard, indicating that senolytics can decrease risk of death in old mice.

It was noted that additional research is required to determine if the compounds are safe and effective in clinical trials involving humans; and current and future preclinical studies may show that senolytics may be used to enhance lifespan in the elderly as well as in cancer survivors and others with a range of senescence associated chronic diseases.

Majority of clinical advances wouldn’t be possible without knowledge of fundamental basic research; science is an unpredictable and incremental process with each research advance building on previous discoveries which can happen in unexpected ways. Research provides better understandings of human biology and behavior that is foundation to advancing new and better ways to prevent, diagnose, and treat disease.

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