Cannabidiol (CBD), a non-hallucinogenic compound derived from the Cannabis sativa plant, has become a popular and effective supplement for treating ailments from chronic pain to epileptic seizures, and evidence has emerged that CBD extends the lifespan of specific animal models. Although CBD has shown efficacy in treating a variety of maladies, there is a lack of mechanistic data supporting how these effects are achieved. A recent study published in Geroscience has linked CBD’s lifespan-extending properties to a well-characterized cellular process known as autophagy.
Derived from the Greek word “autóphagos” meaning self-devouring, autophagy is the body’s process of recycling cells or cellular components. This maintenance is critical to cellular health. Many of the interventions known to extend lifespan involve autophagy: methionine restriction depends on it; exercise and intermittent fasting stimulate it. Diminished autophagic processes persistently characterizes aging in all manner of species. Furthermore, genetic modifications designed to upregulate autophagy have been shown to extend lifespan in a variety of lifeforms from yeast to mice.
C. elegans, the animal model for this particular study, is a roundworm frequently chosen for aging experiments due to its short lifespan and readily tractable genetic character, allowing for a variety of experiments designed to parse out the biological underpinnings of an experimental intervention. Previous studies had demonstrated a significant extension of lifespan in C. elegans supplemented with CBD; in this most recent study, the imparted increase in lifespan is shown to be dependent on autophagy and to protect against age-related neuronal degeneration.
Animals treated with CBD were roughly 25% longer lived. To demonstrate that the observed increase in lifespan was dependent on autophagy, investigators genetically inhibited the action of several autophagy genes (bec-1, vps-34, and sqst-1); in doing so, they deterred the CBD-attributed increase in lifespan. Further tissue-specific interrogations revealed autophagy to be markedly increased in neurons and resulted in a morphology more similar to younger neurons. The authors interpret CBD’s activation of autophagy and subsequent improvement to neural systems to be responsible for the increased lifespan seen in these animals.
Lifespan, although an important metric for anti-aging therapies, is strictly a chronological assessment. Healthspan is a functional measure relative to chronological age. Numerous biological parameters decline with age; however, an intervention that is considered to improve healthspan will retain or restore a particular function to a state seen earlier in the lifespan of an organism. In addition to increased lifespan, CBD treatment improved healthspan in several areas, e.g., motility, reproduction, and neuromuscular function. Overall, these data demonstrate that CBD allows animals a functionally higher quality of life for a longer period of time.
Neuronal degradation is characterized as deterioration in both cognitive and neuro-muscular function and is a common hallmark of aging. Delaying this phenomenon could directly increase lifespan; however, the possibility of improved healthspan is equally significant. In human populations, the likelihood of developing a neurodegenerative disease goes up exponentially in aged populations. As an example, consider that the risk of developing Alzheimer’s disease (the sixth leading cause of death in the United States) doubles every five years after the age of 65; with an average life expectancy of roughly 79 years, this is a bleak statistic. As more research focuses on cannabidiol, there presents an opportunity to uncover previously unknown benefits of cannabis-derived compounds to address such issues. Although this study does not suggest a direct link to any particular neurological disease, such as Alzheimer’s disease, the inordinate neurological pathologies as well as non-pathological age-related cognitive decline seen in the elderly suggest a potentially beneficial pharmacological use.