Caffeine extends life span, improves healthspan, and delays age-associated pathology in Caenorhabditis elegans

Abstract

BackgroundThe longevity of an organism is influenced by both genetic and environmental factors. With respect to genetic factors, a significant effort is being made to identify pharmacological agents that extend life span by targeting pathways with a defined role in the aging process. On the environmental side, the molecular mechanisms responsible for the positive influence of interventions such as dietary restriction are being explored. The environment experienced by humans in modern societies already contains countless compounds that may influence longevity. Understanding the role played by common compounds that substantially affect the aging process will be critical for predicting and interpreting the outcome of introducing new interventions. Caffeine is the most widely used psychoactive drug worldwide. Prior studies in flies, worms, and mice indicate that caffeine may positively impact age-associated neurodegenerative pathology, such as that observed in Alzheimer’s disease.ResultsHere we report that caffeine is capable of extending life span and improving healthspan in Caenorhabditis elegans, a finding that is in agreement with a recently published screen looking for FDA-approved compounds capable of extending worm life span. Life span extension using caffeine displays epistatic interaction with two known longevity interventions: dietary restriction and reduced insulin signaling. Caffeine treatment also delays pathology in a nematode model of polyglutamine disease.ConclusionsThe identification of caffeine as a relevant factor in aging and healthspan in worms, combined with prior work in both humans and rodents linking caffeine consumption to reduced risk of age-associated disease, suggests that caffeine may target conserved longevity pathways. Further, it may be important to consider caffeine consumption when developing clinical interventions, particularly those designed to mimic dietary restriction or modulate insulin/IGF-1-like signaling. The positive impact of caffeine on a worm model of polyglutamine disease suggests that chronic caffeine consumption may generally enhance resistance to proteotoxic stress and may be relevant to assessing risk and developing treatments for human diseases like Alzheimer’s and Huntington’s disease. Future work addressing the relevant targets of caffeine in models of aging and healthspan will help to clarify the underlying mechanisms and potentially identify new molecular targets for disease intervention.

Age-associated vulval integrity is an important marker of nematode healthspan

“…They measured healthspan by monitoring worm movement, eating, and stress resistance over time. This is in contrast to prior studies which have reported improvements in nematode healthspan resulting from the same and other longevity-enhancing interventions (Johnson et al 2000;Herndon et al 2002;Huang et al 2004;Kaeberlein et al 2006;Mehta et al 2009;Sutphin et al 2012). A major challenge for these types of studies in nematodes is that healthspan (and health itself) is difficult to define in worms, and each lab uses their own, somewhat arbitrary, healthspan measurements.…”

Caenorhabditis elegans orthologs of human genes differentially expressed with age are enriched for determinants of longevity

“…The efficacy of many longevity interventions is strongly dependent on environmental temperature (Lakowski & Hekimi, 1996; Gems et al ., 1998; Lee & Kenyon, 2009; Leiser et al ., 2011; Sutphin et al ., 2012; Horikawa et al ., 2015; Zhang et al ., 2015). To capture genes that influence longevity across the temperature spectrum, we employed a two‐temperature screening strategy, measuring lifespan of wild‐type (N2) worms subjected to RNAi targeting each gene at 15 and 25 °C.…”

“…Previous work has detailed the role of temperature in specific aging interventions, such as reduced insulin signaling (Gems et al ., 1998), reduced hypoxic signaling (Leiser et al ., 2011), caffeine supplementation (Sutphin et al ., 2012), or disruption of physiological ‘clock’ genes (Lakowski & Hekimi, 1996), among others. Lee & Kenyon (2009) and Horikawa et al .…”

Geroscience: Addressing the mismatch between its exciting research opportunities, its economic imperative and its current funding crisis

“…1 supports the assertion that the types of research advocated above have barely begun. Kudos can be given to such scientists as Monica Driscoll (Onken and Driscoll, 2010), Matt Kaeberlein (Sutphin et al, 2012), Barry Halliwell (Ng et al, 2014), Heidi Tissenbaum (Bansal et al, 2015), Coleen Murphy (Hahm et al, 2015), Malene Hansen (Gelino et al, 2016) and others for having pioneered healthspan research in C. elegans . Let us hope we can see a similar expansion of such research in other model organisms, certainly to include mammalian models (Richardson et al, 2016).…”