How allantoin can potentially extend lifespan, mimicking calorie restriction

  • Calorie restriction has been widely established to help extend life and improve health in animals and humans alike. Some substances, such as resveratrol and pterostilbene among others, are known to mimic calorie restriction and provide valuable anti-ageing benefits.
  • In a recent study it was found that the anti-ageing chemical allantoin, used for decades in cosmetics for it's skin repairing benefits, may also be a caloric restriction mimic substance that extends lifespan.
  • Allantoin is naturally found in comfrey and is the primary reason of it's healing / repair action on skin.
  • For the moment scientists have tested allantoin in nematode worms, on which most life extension experiments initially take place, and have found that allantoin exerts significant life extension and health improvement benefits on those animals.
  • So the next stage is to try allantoin orally in higher animals and humans to examine if it can provide life extending / anti-ageing properties in higher organisms.
  • The good news is that allantoin is already widely available and used in anti-ageing / skin repair creams, and it is super safe and effective.
  • So you don't need to wait for several years for clinical trials to be finalised to use this natural plant chemical. You can use locally it straight away in the form of a cream for it's already known properties on the skin, and if proof of further anti-ageing benefits materialise, this proof can only explain how allantoin works, not if it works :)
  • However, for the moment I would NOT use this plant chemical orally, until solid safety data are available on it's oral use.
  • Source: A network pharmacology approach reveals new candidate caloric restriction mimetics in C. elegans, http://www.ncbi.nlm.nih.gov/pubmed/26676933
  • Abstract: "Caloric restriction (CR), a reduction in calorie intake without malnutrition, retards aging in several animal models from worms to mammals. Developing CR mimetics, compounds that reproduce the longevity benefits of CR without its side effects, is of widespread interest. Here, we employed the Connectivity Map to identify drugs with overlapping gene expression profiles with CR. Eleven statistically significant compounds were predicted as CR mimetics using this bioinformatics approach. We then tested rapamycin, allantoin, trichostatin A, LY-294002 and geldanamycin in Caenorhabditis elegans. An increase in lifespan and healthspan was observed for all drugs except geldanamycin when fed to wild-type worms, but no lifespan effects were observed in eat-2 mutant worms, a genetic model of CR, suggesting that life-extending effects may be acting via CR-related mechanisms. We also treated daf-16 worms with rapamycin, allantoin or trichostatin A, and a lifespan extension was observed, suggesting that these drugs act via DAF-16-independent mechanisms, as would be expected from CR mimetics. Supporting this idea, an analysis of predictive targets of the drugs extending lifespan indicates various genes within CR and longevity networks. We also assessed the transcriptional profile of worms treated with either rapamycin or allantoin and found that both drugs use several specific pathways that do not overlap, indicating different modes of action for each compound. The current work validates the capabilities of this bioinformatic drug repositioning method in the context of longevity and reveals new putative CR mimetics that warrant further studies. "