Senotherapy

Senotherapy is an early-stage basic research field for development of possible therapeutic agents and strategies to specifically target cellular senescence,^[1] an altered cell state associated with ageing and age-related diseases. The name derives from intent of the proposed anti-aging drug to halt "senescence".^[1] As of 2019, much of the research remains preliminary and there are no drugs approved for this purpose.

Types

Senotherapeutics include:

• 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).

• 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]

• Senolytics – small molecules that specifically induce cell death in senescent cells,^[15][16] targeting survival pathways and anti-apoptotic mechanisms,^[17] antibodies and antibody-mediated drug delivery medications. Unlike SASP inhibitors, senolytics can be effective by intermittent rather than continuous application.^[18]

• Senomorphics – small molecules that suppress senescent phenotypes without cell killing^[19]

• Gene therapy strategies – 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^[3][20]

See also

• Geroprotector
• Senolytic

References

Further reading