What are senolytics?
The term senolytics refers to molecules, natural or synthetic, that interact specifically with the body’s senescent cells, leading to their elimination.
Senescent cells are old, no longer functional cells that have also lost the ability to “commit suicide” (in technical jargon, they do not undergo apoptosis); they can, however, release inflammatory molecules and contribute to the aging of tissues and to the onset of clinical conditions associated with aging.
Senolytics are a subgroup of geroprotectors, that is, all those interventions aimed at slowing down aging and extending the life of the organism. Also geroprotectors are the compounds called senomorphics (or senostatics), which are able to block cellular senescence or alter the secreted molecules but which, unlike senolytics, do not induce cell death.
How do senolytic drugs work?
Senolytic compounds act by interfering with the biochemical mechanisms of senescent cells and cause their death.
Since several preclinical studies (in vitro and in animal models) have highlighted the direct link between senescent cells, aging and related clinical conditions, the hypothesis is that intervening with substances with senolytic action could be a strategy to keep the body healthy for longer, also extending its life.
Studies in humans are currently limited and the results are preliminary. Some senolytic compounds may in fact have undesirable side effects, which therefore require careful planning of trials in terms of dosages and timing of administration. At present it is believed, for example, that any senolytic therapy should involve intermittent rather than chronic administration.
What are the senolytic substances?
So far, seven classes of senolytics have been recognized, according to the molecular mechanism on which they act to bring about the death of senescent cells. Among the first senolytics identified are dasatinib (a drug used to treat some forms of leukemia) and quercetin (a natural flavonoid found in fruit and vegetables): their combined administration in preclinical studies has shown benefits for clinical conditions associated with aging such as atherosclerosis, osteoporosis, pulmonary fibrosis and neurodegeneration; more recently, an improvement in health and an extension of average lifespan have been observed in old mice. On this basis, clinical trials in humans have also been launched to verify the effects of the intermittent combination of dasatinib and quercetin on the progression of Alzheimer’s disease and of pulmonary fibrosis.
In addition to quercetin, other natural senolytics are piperlongumine (found in the plant Piper longum), curcumin (which can be extracted from turmeric) and fisetin (which can be found in fruit and vegetables such as strawberries, apples, onions and cucumbers).
Rapamycin, a well-known anti-rejection drug, is showing properties useful for counteracting aging, but it does not kill senescent cells, and therefore must be considered a senomorphic molecule.
