Researchers at Newcastle University have shown that clearing out senescent cardiac muscle cells from the hearts of aged mice restores heart health.
It seems that not a month goes by without a new study showing that senolytics, drugs that remove aged and damaged cells from the body, improve organ or tissue function by reversing some aspects of aging. A new study has shown that removing senescent cells from the hearts of old mice restores heart health and alleviates the detrimental effects of cardiac aging, including myocardial hypertrophy and fibrosis.
What are senolytics?
As we age, increasing numbers of our cells become dysfunctional, entering into a state known as senescence. Senescent cells no longer divide or support the tissues and organs of which they are part; instead, they secrete a range of harmful inflammatory chemical signals, which are collectively known as the senescence-associated secretory phenotype (SASP).
The SASP increases inflammation, harms tissue repair and function, causes the immune system to malfunction, and raises the risk of developing age-related diseases such as cancer. It can also encourage other nearby healthy cells to become senescent via the so-called bystander effect. Therefore, a small number of these cells can cause a great deal of harm.
Normally, senescent cells destroy themselves by a self-destruct process known as apoptosis before being cleared away by the immune system. Unfortunately, as we age, the immune system becomes weaker, and senescent cells start to build up in the body. The accumulation of senescent cells is considered to be one of the reasons why we age and develop age-related diseases.
It has been suggested that the clearance of senescent cells might help address a number of age-related diseases at once, as senescent cells are thought to be one of the fundamental reasons that we age.
Taking out the trash
Researchers at Newcastle University in the UK, in collaboration with Mayo Clinic in the US and Inserm in France, used both a genetic and a small-molecule approach to destroying senescent cells in the hearts of old mice, and the results were impressive. During their study, the research team discovered how heart cells become senescent and demonstrated how aging hearts can be made to work like those of younger mice again.
The researchers showed that while cells become senescent as the result of telomere shortening due to a lifetime of cell division, they also do so due to stress that damages the structure of the telomeres. This may also explain how non-dividing cells in the body age.
Some mice are specially engineered to destroy their senescent cells when given a specific chemical. The researchers were able to clear the senescent cells in the hearts of these mice, and they were also able to clear the senescent cells of normally aged mice by using the cancer drug navitoclax. The researchers found that both genetic clearance and navitoclax significantly reduced hypertrophy and fibrosis in the aged mice. Essentially, the researchers were able to reverse the damage that aging causes to the heart.
The next step for the research team will be to explore the effect of clearing out senescent cells following a heart attack. The hope being that senolytic therapies may also be useful in helping heart attack victims make a better recovery following a cardiac event.
This is yet another example of why senolytics and the removal of senescent cells may be a game changer for heart health. Obviously, this data is from a mouse study, but with human trials for senolytics currently underway, this and other studies raise some exciting possibilities for healthier and longer lives.
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 Coppé, J. P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., … & Campisi, J. (2008). Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS biology, 6(12), e301.
 Coppé, J. P., Desprez, P. Y., Krtolica, A., & Campisi, J. (2010). The senescence-associated secretory phenotype: the dark side of tumor suppression. Annual Review of Pathological Mechanical Disease, 5, 99-118.