Targeting aging-associated pathways: a novel therapeutic approach for cancer

Aging has been found to be associated with the onset and progression of multiple diseases. Anti-aging approaches using natural compounds have been an area of active research, since they focus on restoring the lost cellular homeostasis and regeneration. But diseases like cancer require the exact opposite effect specifically in the affected cells, i.e. the induction of cell death by apoptosis due to induced loss of homeostasis (pro-aging). The present study critically reviews aging related therapeutic approaches in cancer. Interestingly, it has been found that anti-aging approaches can bring therapeutic effects in the early stages of cancer but in the advanced stages of cancer only pro-aging approaches have been observed to deliver therapeutic effects by inducing cellular damage followed by apoptosis in cancer cells. We have extensively reviewed many such pro-aging approaches, including stimulation of mitochondrial dysfunction, oxidative stress and endoplasmic reticulum (ER) stress and impairment of ubiquitin–proteasome system (UPS) and autophagy, that have been shown to induce cell death by apoptosis in different cancer cells and thereby inhibit tumor proliferation. Natural compounds that have been found to stimulate the aforementioned pro-aging pathways may hold a key towards the use of novel therapeutics in combinatorial cancer therapeutics. Many such natural compounds have been reviewed in this study. Some natural compounds including polyphyllins and myricetin have been observed to stimulate multiple pro-aging pathways simultaneously in different cancer cells, thereby producing more robust results. Thus, the present study sheds light on the uncharted potential of natural compounds and aging-related therapeutic approaches in cancer. Graphical abstract