The Role Of Cellular Stress, Jumping Genes, And AMPK In Placental And Embryonic Development

The evolution of the human genome has been facilitated to a great extent by the activity of transposable elements (TEs), also known as “jumping genes”. As the name implies, TEs are DNA sequences capable of moving or transposing from one position in the genome to another and were first described by Nobel laureate Barbara McClintock.

Interestingly, McClintock also indicated that a “genome shock” or stress may induce the mobilization of TEs. Several different stressors (i.e. starvation, heat stress, etc.) are associated with increases in intracellular reactive oxygen species (ROS) and calcium (Ca2+), and cellular stress has been shown to induce TE mobilization in several model organisms and in vitro (i.e. yeast, flies, and mouse cells). ROS also induces mobilization of TEs in human neuroblastoma cells. Additionally, evidence indicates that organisms that reside in stressful environments such as the “African” south-facing slope of “Evolution Canyon” located in Israel (experiences significantly higher levels of solar radiation, drought, and temperature compared to the “European” north-facing slope) may experience enhanced TE activation and mobilization compared to less stressful environments.

Other stressful environments that may also promote TE mobilization and hence organismal evolution include the Galapagos and Hawaiian Islands (both volcanic islands). Strikingly, one of the oldest living non-clonal organisms on the planet, the Great Basin Bristlecone Pine (Pinus Longaeva, > 5000 years), thrives in a harsh environment that includes elevated levels of UV radiation, nutritionally-deprived soils, and harsh temperatures, indicating that cellular stress may not only promote genome evolution and speciation through TE mobilization but may also increase lifespan.

Furthermore, the induction of cellular stress, mediated by increases in ROS and/or Ca2+, etc. may link TE mobilization, lifespan, speciation, and human genome evolution with the creation of human life via AMPK activation. AMPK is an evolutionarily conserved kinase that is present in nearly every eukaryotic organism. AMPK is activated by a wide range of cellular stressors (e.g. temperature variations, starvation, radiation, exercise, etc.) as well as by increases in intracellular ROS, Ca2+, and/or an AMP(ADP)/ATP ratio increase (an indicator of an energy deficit).

AMPK is also activated by a many plant- and bacterial-derived compounds that have demonstrated extensive therapeutic effects in human cells, in animal models, and in humans (e.g. metformin, resveratrol, butyrate, ionomycin, etc.). Indeed, a TE known as L1 is active and capable of mobilization in human oocytes, human sperm, and in human neural progenitor cells. AMPK is found in oocytes and stress-inducing compounds that increase ROS or Ca2+ levels (e.g. menadione) promote oocyte maturation in an AMPK-dependent manner.

L1 depletion also inhibits oocyte maturation. Oocyte maturation precedes and is critical for efficient oocyte activation. Oocyte activation is indispensable for the creation of all human life. Every human being alive today and any human being that has ever lived began their existence as an activated oocyte. Human oocytes can be activated by several stress-inducing compounds that activate AMPK, including A23187, ethanol, and ionomycin. Ionomycin, which has been extensively used during in vitro fertilization procedures to produce normal, healthy children, is an antibiotic produced by certain bacterial strains from the genus Streptomyces. Cellular stress and increases in ROS and Ca2+ have also been shown to increase antibiotic production by Streptomyces, indicating that the beneficial effects of cellular stress cross species boundaries.

AMPK has also been found localized at the acrosome (the head region) of human sperm and ROS and ionomycin induce the acrosome reaction in human sperm. The acrosome reaction involves the releases of enzymes that are critical in facilitating penetration and fertilization of an oocyte by sperm. Interestingly, increases in ROS and Ca2+ also facilitate hippocampal long-term potentiation (LTP, considered a cellular correlate for learning and memory) and AMPK activation has been shown to be required for long-term memory formation, as AMPK inhibition significantly inhibits hippocampal LTP in vitro and long-term memory formation in vivo. The AMPK activator metformin, however, enhances neurogenesis (i.e. generation of new neurons) and spatial memory formation. ROS induces L1 mobility in human neuroblastoma cells and inhibition of L1 mobility impairs long-term memory formation in vivo, providing further evidence that cellular stress-induced AMPK activation facilitates beneficial TE activation and mobilization.

Similarly, stress-induced AMPK and TE activation play critical roles in placental development, as ROS and Ca2+ promote trophoblast differentiation and the expression of syncytin-1, a protein that is derived from a TE and is necessary for the formation of the syncytiotrophoblast (facilitates nutrient and gas exchange between the mother and the fetus). Syncytin-1 is also found in human sperm and the receptor for syncytin-1, ASCT2, is found in and increases on oocyte maturation. Also, AMPK knockdown inhibits trophoblast differentiation, AMPK-activating compounds promote trophoblast differentiation, and increased levels of L1 mRNA have been detected in 3rd-trimester human placentas.

Lastly, the landmark initial sequencing of the human genome revealed that both telomerase (critical for telomere maintenance) and RAG1 (promotes DNA cleavage and transposition) are derived from TEs. Metformin has recently been shown to activate telomerase in an AMPK-dependent manner in human cells and metformin activates RAG1 via AMPK, providing compelling evidence for our novel hypothesis that cellular stress and AMPK activation links “jumping genes” with human genome evolution and the creation of all human life.

These findings are described in the article entitled Transposable elements, placental development, and oocyte activation: Cellular stress and AMPK links jumping genes with the creation of human life, recently published in the journal Medical Hypotheses. This work was conducted by Jahahreeh Finley from Finley BioSciences.

About The Author

Jahahreeh Finley

Jahahreeh Finley is an accomplished life science patent attorney who has also recently authored several publications that will likely have an immeasurable impact on the assessment of disease etiology.

In 2014, Jahahreeh was the first person to publish that metformin, a commonly prescribed anti-diabetic drug, will ameliorate accelerated aging defects in cells from children with the genetic disease Hutchinson-Gilford progeria syndrome (HGPS) & beneficially alter a gene splicing factor that is dysregulated in HGPS. This hypothesis was substantiated in 2016, with metformin alleviating accelerated aging defects in HGPS cells & beneficially altering the same gene splicing factor that was hypothesized by Jahahreeh in 2014. Normal humans also produce the same toxic protein via the same faulty gene splicing method that causes accelerated aging in HGPS patients, making the substantiation of this hypothesis relevant for normal aging as well.

In 2015, Jahahreeh was also the first person to publish that HIV-1 latency & HGPS are connected by the same protein that metformin has been shown to primarily activate, called AMPK. Recent evidence has substantiated this hypothesis, with metformin having been shown to activate AMPK, inhibit the same splicing factor that is dysregulated in HGPS & HIV-1 latency, decrease the levels of the toxic protein progerin in HGPS cells, & destabilize latent HIV-1 (facilitating immune system detection & destruction).

In 2016, 2017, & 2018, Jahahreeh was the first person to publish that the same protein (AMPK) that connects HGPS & HIV-1 latency also links "jumping genes" & telomerase with the activation of human oocytes, a prerequisite for the creation of all human life. This hypothesis has also been substantiated, with the antibiotic ionomycin having been shown to activate AMPK, efficiently promote HIV-1 reactivation, activate "jumping genes", & induce human oocyte activation during IVF procedures, producing normal, healthy children.

Speak Your Mind!


Some Animals Can Cope With Noise, While Others Cannot

Human-generated, or anthropogenic, noise has gained a lot of research attention lately. It tracks human expansion and spreads throughout both terrestrial and aquatic habitats, leaving potential ecological catastrophes in its wake. Noise affects many aspects of animal life from fish foraging behavior to nesting success in birds. However, our understanding of how some animals may […]

The Driving Forces Of China’s Rapid Urbanization From 1949 To 2015

Since the foundation of People’s Republic of China in 1949, Chinese cities have experienced rapid development. Various policies and socioeconomic forces drove the development in the 70 years. Researchers from China, U.S., and U.K. reviewed historical documents and public data. They identified four distinct urbanization stages as well as the driving forces in the four […]

Michael Bloomberg, Former New York Mayor And Billionaire, Pledges $4.5 Million Towards Paris Deal After Trump’s Withdrawal

Michael Bloomberg has pledged $4.5 million towards the Paris Deal that the United States withdrew from the deal that aims to prevent, or at the very least slowdown, the effects of climate change due to human activity. The former New York Mayor believes that it is part of his responsibility to help this deal succeed […]

A Better Look At Asteroid 216 Kleopatra

Nearly 4.6 billion years ago, the Solar System began forming from a disk of material that surrounded a new star – our Sun. The transition from debris disk to the planets we see is an active area of investigation, but most planetary scientists agree that there was a series of intermediate stages which included the […]

Comparison Of Dietary Fibre Composition Of Old & Modern Durum Wheat Genotypes

As the dominant staple crop in temperate regions of the world, wheat provides between 20% to 50% of the total intake of calories in our diets. Most of the global wheat crop is bread wheat, but durum wheat is grown in regions with a Mediterranean climate and used particularly for making pasta. Modern intensive plant […]

College Drinking Culture In Spain, Argentina, And The USA: An Examination Of Impulsivity, College Alcohol Beliefs, And Alcohol Outcomes

Across many countries and cultures, college students drink heavily. Students who drink heavily are at risk for a wide range of problems ranging from a hangover to unsafe and unplanned sex, and from poor academic performance to developing an alcohol-use disorder. Decades of research has found college student drinking culture to be a barrier towards […]

How Winter Soil CO2 Fluxes Respond To Altered Snow Depth In A Temperate Forest Ecosystem

Climate change models suggest that the average temperature of the Earth’s atmosphere will gradually increase 2~5 °C over the next decades. The depth of snow cover may change under global warming scenarios, especially in mid-temperate ecosystems, which may significantly affect soil carbon fluxes in winter. Previous studies have demonstrated that winter soil carbon emissions can […]