Senescents are a new class of drugs developed to combat one of the key mechanisms of ageing - the accumulation of ageing cells (senescent cells). These cells, although they do not divide, remain metabolically active and secrete a number of pro-inflammatory factors that disrupt tissue function and contribute to age-related diseases such as atherosclerosis, osteoporosis and neurodegenerative diseases. Understanding how to eliminate these cells or modify their activity can significantly improve tissue health and delay the ageing process.
Mechanism of action of ageing cells
Ageing cells arise as a result of various stress factors, such as DNA damage, telomere shortening and oxidative stress. At the molecular level, activation of signalling pathways, such as p16^INK4a^ and p21, causes cell cycle arrest. During this phase, these cells enter a senescent state, but are not eliminated by natural mechanisms, resulting in their accumulation in tissues. Ageing cells are characterised by the so-called SASP (Senescence-Associated Secretory Phenotype), which includes the secretion of pro-inflammatory cytokines, chemokines and enzymes that degrade the extracellular matrix.

The role of ageing cells in age-related diseases
- Atherosclerosis: Accumulation of ageing cells in blood vessel walls leads to endothelial dysfunction and chronic inflammation, which accelerates the development of atherosclerosis.
- Osteoporosis: Ageing osteocytes reduce osteoblast activity, which weakens bone structure, increasing the risk of fractures.
- Neurodegenerative diseases: In the brain, ageing glial cells, such as microglia and astrocytes, contribute to increased inflammation, which is associated with the progression of Alzheimer's disease.
- Tissue fibrosis: Ageing fibroblasts may contribute to pathological collagen deposition, leading to lung, liver and kidney fibrosis.
Senotherapeutics: a new approach to anti-ageing therapies
Senotherapeutics are divided into two main groups:
- Senolytics: Drugs that selectively eliminate ageing cells by inducing apoptosis. Examples include dasatinib, quercetin, fisetin and navitoclax. The action of senolytics is based on inducing cellular stress in ageing cells, which leads to cell death.
- Senostatics: Substances that reduce SASP secretion without eliminating the ageing cells. Examples include metformin and rapamycin, which inhibit the activity of the mTOR pathway, reducing inflammation in tissues.
Overview of key senotherapeutics and their potential
- Dasatinib and Quercetin: The combination of these two senolytics was effective in eliminating ageing cells in models of pulmonary fibrosis and osteoporosis, improving tissue health.
- Fisetin: A natural flavonoid present in the fruit that exhibits potent senolytic activity, reduces inflammation and improves metabolic health.
- Navitoclax: Inhibitor of BCL-2 family proteins that eliminates ageing cells in models of neurodegenerative diseases.
- Gingerenone A: An active ingredient isolated from ginger that reduces the lifespan of ageing cells by activating caspase-3 and reducing the expression of pro-survival proteins.
Results of clinical trials on senotherapeutics
Clinical trials with dasatinib and quercetin for the treatment of idiopathic pulmonary fibrosis have shown improved respiratory function and reduced tissue inflammation. Studies in animal models have shown that elimination of ageing cells improves tissue health, delays the ageing process and prolongs life.
Senotherapies in clinical practice: challenges and future applications
The biggest challenge in the use of senotherapeutics is to ensure their selectivity and safety. Senolytics can lead to the elimination of healthy progenitor cells, which affects the ability of tissues to regenerate. Personalisation of therapy, taking into account specific pathologies and tissue types affected by ageing, may prove to be the future of senotherapy.
Future directions for senotherapeutics research
Future research will focus on:
- Identification of new senolytics: The search for compounds with greater selectivity and less toxicity.
- Combination therapies: Investigating the synergistic effects of senotherapeutics with other anti-ageing interventions such as diet, intermittent fasting or epigenetic modulators.
- In vitro and in vivo modelling: Use of advanced animal models and organoids to test the efficacy and safety of new senotherapeutics.
Senotherapeutics represent a promising strategy in the fight against age-related diseases. Their ability to selectively eliminate ageing cells or modulate their activity may be crucial for future anti-ageing therapies. However, further research is still needed to better understand their effects on the body and determine the optimal way to use them.
Sources:
- Identification of gingerenone A as a novel senolytic compound
- A proteomic atlas of senescence-associated secretomes for aging biomarker development
- A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study