New Harvard Study shows for the first time that meditation upregulates genes in the AMPK pathway similar to metformin

A new study published in 2018 by researchers at Harvard Medical School showed for the first time that a collection of meditative techniques that led to the relaxation response (RR) in human patients significantly upregulated genes in the AMPK signaling pathway [1]. The RR elicitation routine included diaphragmatic breathing, body scan, mantra repetition, mindfulness meditation, and passively ignoring intrusive thoughts [1]. An upregulation of genes in the AMPK signaling pathway was detected via blood samples taken from patients in which total RNA was isolated from peripheral blood mononuclear cells (PBMCs) [1].

This study has an interesting connection to a recently published study in 2018 in which a retreat that included meditation led to an increase in the RNA-binding protein HnRNPA1 [2]. I first hypothesized and proposed that metformin and AMPK activation would beneficially modulate the activity of HnRNPA1 [3,4] . Indeed, the well-studied AMPK activator resveratrol has recently been shown to upregulate HnRNPA1 [5]. Additionally, HnRNPA1 binds to telomerase and plays a critical role in telomere maintenance, promotes latent HIV-1 reactivation (facilitating immune system detection and virus destruction), and is necessary for the transposition or “jumping” of “jumping genes” in human cells [6-9]. Metformin has also been shown to activate human telomerase (hTERT) in an AMPK-dependent manner and reduce cellular makers associated with latent HIV-1 in infected patients [10-12]. This evidence lends substantial support to several hypotheses that I originally proposed linking metformin and AMPK activation with telomerase activation, “jumping genes” in the brain (important for learning and memory), virus destruction, aging deceleration, human life creation, and even consciousness itself [3,4,13-17]. Strikingly, AMPK activation may also play a critical role in the beneficial effects of meditation on the human brain. 

Meditation has been shown to increase brain gamma waves, brain gray matter density, and beneficial transcriptome changes in energy metabolism [18-20]. Interestingly, the Dalai Lama has also described meditation as “hard work”, indicating that meditation is an active process that challenges or slightly stresses the brain, leading to upregulation of genes in the AMPK signaling pathway as shown in the Harvard study [1]. This “mental stressor or challenge” is very much similar to challenging or stressing the human body with exercise, which is well-known to induce AMPK activation, leading to several beneficial effects [21]. The “mental challenge of meditation” is also analogous to the stress or challenge placed on the brain of animals when exposed to a stimulating environment, leading to an enhancement of learning and memory (i.e. long-term potentiation) and the “jumping of genes” [15,16]. Additionally, methodologies and neurotransmitters that are critical for inducing long-term potentiation (e.g. glutamate, high-frequency stimulation) activate AMPK in neurons and nearly every anesthetic used clinically to induce and maintain general anesthesia, including propofol, activates AMPK and excites the brain in low doses (called paradoxical excitation) [15,16]. Nearly every neurotransmitter that plays a critical role in wakefulness, arousal, and cognition also activates AMPK, supporting my original hypothesis that AMPK activation likely plays a central role in promoting consciousness itself [16].

Source: By ISAF Headquarters Public Affairs Office (originally posted to Flickr as 100410-F-7713A-002) [CC BY 2.0 (https://creativecommons.org/licenses/by/2.0)], via Wikimedia Commons; By Anatomist90 [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], from Wikimedia Commons

References:

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