The impact of opioids on the hallmarks of ageing.

Opioids rank among the most hazardous substances of abuse, leading to opioid use disorders (which greatly diminish life quality) and contributing to the highest drug-related mortality rates. Nonetheless, both the therapeutic and recreational use of opioids is escalating globally. Interestingly, chronic opioid users often exhibit signs consistent with accelerated ageing, suggesting that they likely interfere with well-characterized ageing mechanisms (e.g., telomere shortening, epigenetic changes, mitochondrial dysfunction, cellular senescence). Here, we review the most recent advances regarding the impact of opioids on well-characterized hallmarks of ageing, to ascertain a potential association between opioid use and accelerated ageing. Our findings indicate that there is accumulating evidence supporting a close association between the use of opioids and the early onset of some ageing hallmarks, namely mitochondrial dysfunction, genomic instability, or telomere shortening. However, there is still limited data available regarding how opioids specifically impact other ageing hallmarks, like nutrient sensing, cellular senescence, or loss of proteostasis. Taking into consideration the high prevalence of opioid use, strengthening the understanding of the mechanisms underlying opioids' impact on ageing assumes utmost relevance, both in terms of improving risk assessment, as well as to help researchers and clinicians prevent or mitigate these effects in clinical settings.