Senotherapeutics

Senotherapeutics refers to therapeutic agents and strategies that specifically target cellular senescence,^[1] an altered cell state associated with ageing and age-related diseases.

Types

Senotherapeutics include:

1. Geroprotectors – agents/strategies which prevent or reverse the senescent state by preventing triggers of cellular senescence, such as DNA damage,^[2][3][4] oxidative stress,^[5] proteotoxic stress,^[6] telomere shortening ^[7] (i.e. telomerase activators).
2. SASP inhibitors – agents interfering with pro-inflammatory senescence‐associated secretory phenotype (SASP)^[8][9] production, including:
   1. Glucocorticoids as potent suppressors of selected components of the SASP^[10]
   2. Statins such as simvastatin, that can reduce the expression of pro-inflammatory cytokines (IL-6, IL-8, and MCP-1)^[11]
   3. JAK1/2 inhibitors such as ruxolitinib^[12][13]
   4. NF-κB and p38 inhibitors
   5. IL-1α blockers
   6. Mitochondrial depleters in the case of impaired mitophagy^[14]
3. Senolytics – small molecules that specifically induce cell death in senescent cells,^[15][16][17] targeting survival pathways and anti-apoptotic mechanisms, antibodies and antibody-mediated drug delivery medications.
4. Agents/strategies which can enhance immune clearance of senescent cells (an ageing immune system likely impairs senescent cell clearance leading to their accumulation^[18][19]), immune system cells (NK cells, B cells, T cells).
5. Gene therapy agents/strategies intended to edit the genes of the cells of an organism in order to increase their resistance to aging, senile diseases and to prolong the life of the organism^{[20][21][22][23][24][25][26][27][28][29][30]}

References

Further reading

• Kirkland JL, Tchkonia T (2016). "The Way Forward: Translation". Advances in Geroscience. Springer International Publishing: 593–622. ISBN 978-3-319-23245-4. doi:10.1007/978-3-319-23246-1_19. Retrieved 2016-03-13. 
• Soto-Gamez A, Demaria M (2017). "Therapeutic interventions for aging: the case of cellular senescence". Drug Discovery Today. doi:10.1016/j.drudis.2017.01.004.