Table 1.

Workshop Conclusions

• Several drugs and other compounds kill senescent cells (senolytics) or suppress their senescence-associated secretory phenotypes (senomorphics).

• Cellular senescence is implicated in numerous age-related conditions. Planning for repurposing a drug with senolytic or senomorphic effects should consider potential impacts on more than one condition.

• Because components of senescence-associated pathways affect other processes, candidate drugs’ specificity for senescent vs nonsenescent cells should be assessed.

• Anticancer drugs with favorable profiles of senolytic effects vs broader cytotoxic effects may be promising candidate senolytic treatments.

• Because senescent cells do not proliferate and do not need to be fully eradicated, lower doses and intermittent treatment in repurposing cancer drugs as senolytics may reduce toxicity, but benefits need to be weighed against potential risks.

• Senomorphic drugs that do not kill senescent cells would need to be administered continuously, and hence require better safety profiles.

• Analyses of data or specimens from previous trials of compounds considered for repurposing as senolytics or senomorphics could inform trial designs by identifying affected pathways or phenotypes.

• Markers to distinguish senescent cell types in different human tissues are needed to clarify their relationships to differing conditions that could be targeted in clinical trials.

• Markers of specific senescent cell types that can be assessed repeatedly are needed in clinical trials to screen for individuals with high senescent cell burden, assess target engagement, measure elimination of senescent cells or modulation of their phenotypes, and determine schedules of intermittent treatment by measuring rate of disappearance and re-accumulation of senescent cells.

• Validated circulating indicators of senescent cell type and burden are needed for tissues that cannot be feasibly sampled in trial screenees or participants.

• Given the prevalence of multimorbidity and polypharmacy among older persons, consideration is needed regarding senolytic and senomorphic drug–drug and drug–disease interactions, potential contraindications, and implications for drug scheduling.

• It is important to assess off-target effects, the extent to which treatment effects are mediated by effects on cell senescence, and effects on a variety of aging-related changes, risk factors, and other aging mechanisms influenced by cell senescence.

• Standardized measures across studies would enhance comparability of results of interventions and pooled data analyses to provide greater power for assessing intervention effects.

• Additional characterization of human senescent cell types and senescence-associated secretory phenotype components, and their physiologic and clinical effects, is needed for developing senolytic or senomorphic drugs with improved efficacy and safety and testing them in clinical trials.