Researchers believe the key to anti-aging may be the removal of senescent cells
Rideeta Raquib ‘19
As individuals age, the ability of tissues to carry out adequate function deteriorates and age-related diseases become more prominent. Senescent cells are found in huge quantities of these diseases, but there is not much research done regarding whether these cells caused such degeneration. Senescence occurs when cell division is halted in healthy cells due to exposure to prolonged stress and through the action of p16lnk4a and p21Cip1, molecular alterations that cause cell arrest. Although the idea of eliminating age is still a fantasy, researchers at Erasmus University Medical Center in the Netherlands proposed a means of removing senescent cells in order to retain youth.
The research team analyzed senescence in mice models, whereby it was found that clearing senescence indeed delayed a decline in health. Next, the prospects for developing therapeutics were undertaken. The two approaches for senescence clearance were treatment with quercetin or dasatinib and pan-B-cell-lymphoma (pan-BCL) inhibitors ABT-263 or ABT-737. Quercetin, a compound found in fruits and vegetables, has been previously associated with anti-aging properties. Dasatinib is an inhibitor of the Src kinase family and can be used against acute myeloid and lymphoid leukemia because Src kinase proteins are present in certain cancers. Both of these compounds are not specific to senescence and thus were not the best solution. The pan-BCL inhibitors, however, were discovered to be selective against senescent cells and cancers. Negatively, BCL-2 inhibits apoptosis, which could be harmful to other cell types. The ideal compound that could be employed for anti-aging therapy is one that both targets senescence with specificity and stimulate rejuvenation. FOXOs are cell cycle inhibitors present in flies, nematodes, and mammals. These inhibitors can target insulin or insulin-like growth factor pathways, as well as mediate antioxidant response and repair DNA damage. Targeting FOXOs can be a plausible way to eliminate senescence.
Overall, targeting senescent cells is a possible way to tackle aging, but there is much more research to be done to narrow down compounds that contain therapeutic properties. Discovering a therapy will not only lead to anti-aging, but reduce many of the health risks associated with age.
- Peter L.J. de Keizer, The fountain of youth by targeting senescent cells?. Trends in Molecular Medicine doi: 10.1016/j.molmed.2016.11.006.
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