Tag Archive : science

Time Is On My Side….Yes, It Is

The Durk Pearson & Sandy Shaw®life-extension-book
Life Extension NewsTM
Volume 20 No. 2 • March 2017

TIME IS ON MY SIDE … YES, IT IS

by Sandy Shaw

The difference between drug use and addiction or eating and metabolic diseases is time. The amount of time we take a potentially addictive drug determines whether we become addicted; this is also true for eating—eating for only a limited period of time can prevent the development of metabolic diseases, such as diabetes type 2 (Hatori, 2012).

An example of how time can determine the result of eating: a recent study of male mice fed a high fat diet found that restricting feeding to only eight hours a day WITHOUT REDUCING CALORIES as compared to being free to eat at any time prevented metabolic diseases (such as obesity, hyperinsulinemia, fatty liver, and inflammation).

Dopamine is required for the estimation of time by the internal clock. “Interval timing, the ability to discriminate durations in the seconds-to-minutes range, is a form of temporal cognition that requires an optimal level of dopaminergic function in cortico-striatal circuits in order to control time sharing and regulate clock speed.” A time interval is initiated by cortical oscillators in the ventral tegmental area of the brain by a burst of dopamine accompanied by a burst of theta power, which act as the “start gun” (Kononowicz, 2015).

The internal clock is critically controlled by dopaminergic agonists and antagonists. Dopamine agonists such as cocaine and methamphetamine (“speed”) have been shown to increase the speed of the internal clock, while dopamine antagonists such as haloperidol and raclopride have been shown to decrease the speed of the internal clock (Cheng, 2007).

In another study (Sysoeva, 2010), researchers found that there is an association of serotonin (5-HT) related genes with time perception. In their experiment, forty-four Russian Caucasian males (right handed and with a mean age of 22) compared two durations (they had to indicate which of them was shorter) on a computer monitor. “Many studies have reported an association between duration representation parameters and personality, specifically impulsivity and psychoticism.” Unsurprisingly, other studies have found psilocybin, a 5-HT (serotonin) receptor agonist, to affect time perception (Sysoeva, 2010).

“Despite the evidence … suggesting the centrality of DAergic [dopaminergic] modulation in mediating the drug-induced euphoria and timing distortions reported here, this explanation is likely an oversimplification of the processes underlying the individual differences observed in this study. Neuromodulators such as serotonin, GABA, glutamate, and norepinephrine, have also been found to influence time perception and to interact with DA [dopamine] in complex ways (Lake, 2013).” Another neuro­transmitter with important effects on drug addiction and incentive-motivated behaviors is acetylcholine (Lester, 2010).

WHEN TIME SLOWS DOWN

You’ve all experienced it—the times when sudden danger appears, such as your car is about to hit a tree, and time slows release of adrenaline as you rapidly close in on the tree. As explained above, stimulants such as methamphetamine cause a large release of dopamine and this increases the speed of the internal clock. A hypothesis proposes that the reason this feels like time is slowing down is that your brain sees time as the amount of information it processes—the more bits of information is counted as a longer period of time compared to the usual number of bits you experience as “regular” time (Eagleman, 2005).

In a similar fashion, seeing an event in “slow motion” causes observers to believe that more time had passed than actually had (Caruso, 2016). Thus, time is under­estimated.

A very recent paper (Soares, 2016) reported how mice judged the passage of time (judging the duration of intervals). Using a pharmacogenetic method to suppress dopaminergic neuronal activity in the substantia nigra pars compacta, they found that “[s]ituations in which DAergic [dopaminergic] activity is elevated naturally, such as states of high approach motivation, response uncertainty, or cognitive engagement are associated with underestimation of time. Conversely, situations that decrease DAergic activity, such as when fearful or aversive stimuli are presented are associated with overestimation of time.”

The bottom line: “… pleasurable events boost dopamine release, which should cause your internal clock to run faster … so that short intervals seem longer than they are (Simen, 2016).”

FLOW

Time stands still if you go fast enough.

—Stephen F. Kaufman, marial arts professional (Ch.
19 in his book “The Way Of The Modern Warrior”)

Who hasn’t experienced FLOW? The trick is being able to produce it when you want it.

Flow is often described as a state of effortless concentration so deep that people who experience it lose their sense of time. It gives you a sense of acting without conscious awareness, of time slowing down, of perceiving yourself to be moving through a dreamlike state.*
Szxycj at English Wikipedia We knew a highly skilled champion racecar driver (Mickey Thompson) who told us that using a Lift formulation of ours had, in a very long off-road auto race (the BAJA 1000, when it was 1000 miles rather than 1000 kilometers) resulted in time slowing down, with everything happening exactly right and without any conscious effort on his part. He said that it felt like the flow he had experienced in his best races.
The formulation that Mickey took was one of those we designed for our own use that contains the amino acid phenylalanine. Phenylalanine can be converted into tyrosine (which is then converted to dopamine) but also into phenethylamine (also called phenylethylamine), a neuromodulator that provides mental energy like caffeine, but also acts as a stimulus barrier (helps to filter out distractions). Phenylalanine is found in our Lift formulas.

Caffeine provides mental energy in a different way than phenylalanine (see above). Phenylalanine is a natural compound that increases dopamine (via conversion to tyrosine) but, unlike caffeine (a xenobiotic), it does not mimic the effects of amphetamine and cocaine, like caffeine can do at 4-5 times the average human consumption of coffee. At high doses (300-800 mg), caffeine can increase feelings of anxiety, nervousness, and insomnia. Caffeine does NOT have addictive potential at the usual level of human consumption (50-300 mg or 1-3 cups of coffee), but induces feelings of well-being, alertness, energy, and ability to concentrate. Most of the effects of caffeine are reported to take place at adenosine receptors, where caffeine is an inhibitor (Nehlig, 2000). There are other changes, though, which include a 26-30% increase in the densities of cortical muscarinic and nicotinic cholinergic receptors; the evidence supports significant alterations in adenosine, adrenergic, serotonergic cholinergic, and GABAergic systems (Shi, 1993).

NUTRIENTS THAT MODIFY THE SPEED OF THE INTERNAL CLOCK

The amino acid tyrosine is precursor to dopamine, that is, converted to dopamine. (The amino acid phenylalanine is converted to tyrosine, so it is an indirect precursor to dopamine.) As noted above, dopamine agonists increase the speed of the internal clock (Cheng, 2007; Meck, 1987). This feels like time is slowing down. (Interestingly, “flow” is a process in which time does feel as though it is slowing down.)

WHEN PLEASURE BECOMES A HABIT

In the scientific literature, addiction is often called habit formation. Habit formation differs immensely from goal-directed activity. Where goal-directed activity is influenced by the outcome of performing an action, addictive activity is not—a negative outcome does not influence it.** If an action is habitual, “then devaluation should have no effect on performance, since habits are elicited by antecedent stimuli which are not affected by devaluation. “… habitual behavior is not controlled by the action-outcome contingency … (Yu. 2009)”

This can be seen in lever pressing by experimental animals. “At first lever pressing is goal-directed and sensitive to manipulation like outcome devaluation. Under certain conditions, it can become more habitual and impervious to changes in the value of the outcome … Studies in flies, mice, rats, horses, monkeys, and humans have shown some version of this transition from more flexible and goal-directed behavior to inflexible and habitual behavior.” (Yu, 2009)

It was purely the feeling that had captivated me, made me sacrifice everything to it, gladly, joyfully. It was a seashell’s pristine whisper in my ear, warm sun rising in my heart, fireflies winking in the nerves.

—Will Bohnaker, Haunts of The Aardwolf, on the allure of caffeine

EATING: DELAY DISCOUNTING

A recent paper (Johnson, 2010) points to a proposal that “deficits in reward processing may be an important risk factor for the development of obesity, and that obese individuals may compulsively consume palatable food to compensate for reward hyposensitivity.” This is another way of saying “self-medication.”

The dopaminergic nervous system is critically involved in the perception of pleasure from eating and sex. In fact, “the degree of pleasure from eating correlates with [the] amount of dopamine release (Stice, 2008).” The chronic overeating of high fat and high sugar foods causes a decrease in the sensitivity of dopaminergic neurons as a result of downregulation (reduced signaling). Animal studies have found similar effects from overeating and also in response to chronic drug use. Both overeating and the use of addictive drugs cause downregulation of dopamine D2 receptors and decreased D2 sensitivity.

A deficiency in the release of dopamine in the dorsal striatum may also be seen in individuals with a certain variant (allele) of the D2 dopaminergic receptor gene, the Taq1A A1 allele; it is interesting to note that this allele is involved in impulsivity, which is defined as “the relative preference for a smaller reward, sooner in time, compared to a larger reward, later in time … (Eisenberg, 2007)” This is called delay discounting—and “non-human research suggests that corticostriatal mesolimic substrates mediate delay discounting performance and that dopamine is the critical neurotransmitter involved.” (Eisenberg, 2007) The famous marshmallow experiments were a particularly notable example of delay discounting.

MONOAMINE OXIDASE A (MAOA) AND IMPULSIVITY

Monoamine oxidase A (MAOA) is a gene importantly affecting impulsivity. “… the risk imparted by the specific genetic variation studied here [MAOA] contributes to the impulsive dimension of this complex behavior [aggression].” The monoamine oxidase A (MAOA) gene, is of two types—MAOA-L (the low expression variant) and MAOA-H (the high expression variant). MAOA-L is associated with an increased risk of violent behavior. “Arguably, the clearest link between genetic variation and aggression exists for monoamine oxidase A (MAO-A) … a key enzyme in the catabolism [breakdown] of monoamines, especially serotonin.” The enzyme catabolizes dopamine, serotonin, and norepinephrine, reducing their availability for signaling at neuronal synapses (Meyer-Lindenberg, 2006). Hence, reduced catabolism, as with the MAOA-L variant, will not decrease the availability of dopamine, serotonin, and norepinephrine for signaling as much as the MAOA-H variant.

Goal-directed dimensions of aggression have been associated with psychopathy, often accompanied by diminished empathy and remorse. In their study (Meyer-Lindenberg, 2006), the researchers found that “men, but not women, carrying the low-expression MAOA genotype showed increased [emotional] reactivity during retrieval of negatively valenced emotional material.” Interestingly, men have only one allele (copy) of the MAOA gene, whereas women have two. The reason for this is that men have only one X chromosome (where the MAOA gene is located), while (of course) women have two. Interestingly, estrogens have been shown to affect the expression of MAOA in the brain (Meyer-Lindenberg, 2006).

Higher dominance has been associated with the low expression variant of MAOA (MAOA-L) and aggression in males in studies of primates.

SEROTONIN AND IMPULSIVITY

As noted above, serotonin deficiency is associated with impulsive behavior. This can be corrected by taking tryptophan, the amino acid that is converted to 5-hydroxytryptophan by the enzyme tryptophan hydroxylase and then to serotonin. However, some individuals are unable to make this conversion in sufficient amounts because their version of the enzyme lacks adequate potency. A way to overcome this is to take 5-HTP (5-hydroxytryptophan), which bypasses the need for tryptophan hydroxylase. We suggest taking 25 to 50 mg of 5-HTP at bedtime. We get ours from our Serene Tranquility with 5-HTP.™

DELAY DISCOUNTING MEETS THE GRASSHOPPER AND THE ANT
The Ant and the Grasshopper Another experiment on delay discounting (like the marshmallow experiments) was performed in human subjects, who made a series of choices between early and delayed monetary rewards while they were examined by fMRI (functional magnetic resonance imaging) (McClure, 2004). As a result, the researchers developed a hypothesis for how the brain decides between the early and later rewards. “… we hypothesize that short-run impatience is driven by the limbic system, which responds preferentially to immediate rewards and is less sensitive to the value of future rewards, whereas long-run patience is mediated by the lateral prefrontal cortex and associated structures, which are able to evaluate trade-offs between abstract rewards, including rewards in the more distant future.”
They allude to the metaphor of the grasshopper and the ant. The grasshopper spends its time enjoying the present and ignoring what may come later, while the patient ant works diligently preparing for the future. The authors call delay discounting the competition between the “impetuous limbic grasshopper” and the “provident prefrontal ant.” (McClure, 2004).”

In sum, the researchers suggest that “human behavior is often governed by a competition between lower level, automatic processes that may reflect evolutionary adaptations in particular environments, and the more recently evolved, uniquely human capacity for abstract, domain-general reasoning and future planning.”

Another hypothesis on the neuro­chemistry of delay discounting (Kravitz, 2012) proposes that addiction (in which the future consequences of using drugs are ignored) depends upon the interaction between dopamine D1 receptors and dopamine D2 receptors: dopamine D2 receptors counteract dopamine D1 receptors in determining the probability of performing a future action. The D1 receptors induce persistent reinforcement, while the D2 receptors induce transient “punishment” (negative signaling) for the performance of a future action. “In contrast, depression is marked by impaired reinforcement from positive stimuli and heightened punishment from negative stimuli (Kravitz, 2012).”

SPEAKING OF ANTS …

Yes, speaking of ants, a recent paper appeared in the “Research Highlights” section of the 29 Sept. 2016 Nature which reported that ants can get hooked on morphine. The ants were given access to sugar water laced with morphine. Then, over the course of several days, the amount of sugar in the water was reduced while the morphine content was increased, until eventually there was NO sugar in the water, only morphine. The ants, given a choice between sugar water and the sugar-free morphine solution, preferred the sugar-free morphine by 65% to 35%. Plus the ants’ brains showed elevated levels of dopamine, just as addicted mammals do. The authors were said to suggest that ants might make a good model for studying addiction in humans. Durk wonders why 35% of the ants DIDN’T choose morphine … Sandy suggests that maybe those ants had a different version of the D2 dopamine receptor.

HIGH IMPULSIVITY PREDICTS THE SWITCH TO COMPULSIVE COCAINE-TAKING

Rats, like humans, can get addicted to drugs. When rats are exposed to cocaine, 15-20% of them become addicted, which is similar to that observed in humans (Belin, 2008).

“… the essential feature of addiction … [is] … the persistence of drug-seeking in the face of negative consequences …” explain researchers in a 2008 paper (Belin, 2008). In their study, they found that high impulsivity “predicts the development of addiction-like behavior in rats … [and they note that, in humans,] … there is a high comorbidity between drug addiction and disorders characterized by impulsive behavior, such as attention deficit-hyperactivity disorder.”

Low serotonin levels are thought to be a cause of impulsivity. For example, reducing serotonin levels by tryptophan-restricted diets results in more impulsive choices in experiments. A recent paper (Bevilacqua, 2010) found that a mutation in the serotonin 2B receptor predisposed a Finnish population to severe impulsivity.

Lithium may reduce impulsivity, but studies reporting this association have involved doses much higher than the low-dose form that we use. One such study (in rats) found that a “moderate” dose of lithium (20 mg/kg) suppressed impulsive behavior (Ohmura, 2012). Research involving the low concentrations of lithium found in mineral waters and in some tap water has reported reduced impulsiveness and suicide in people.

Another way to reduce impulsivity is to take tryptophan (precursor to serotonin). See above in “Eating: Delay Discounting.”
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*Any testimonials on this web site are based on individual results and do not constitute a guarantee that you will achieve the same results.

Life Priority Meets Mavericks of the Mind

*We found this thought-provoking article on consciousness by David Jay Brown from his blog and thought it would be very informational.

Mavericks of the Mind

Thought Provoking Interviews on Consciousness by David Jay Brown

life-extension-bookDurk Pearson and Sandy Shaw co-authored two of the first and most widely read books on the subject of human longevity–Life Extension: A Practical Scientific Approach and The Life Extension Companion–which triggered a large amount of popular interest in the subject (including my own), and their many television talk show appearances have reached a large number of people over the years.

Although, perhaps, the ultimate goal of medicine all along, the idea of extending human life in otherwise healthy individuals was a relatively novel concept for most people when Pearson and Shaw published their first book back in 1982. How many people could have predicted back in the early eighties that in just a few years after the publication of Pearson and Shaw’s groundbreaking book that there would be such a huge worldwide interest in life extension, anti-aging, and preventative medicine? Pearson and Shaw were not surprised by this new and growing interest and had, in fact, been anticipating it.

Pearson and Shaw have been studying life extension since 1968. They are largely self-educated. Pearson graduated from MIT with a triple major in physics, biology, and psychology, and Shaw graduated from UCLA with a double-major in chemistry and zoology. However, most of their knowledge comes from consuming scientific and medical journals with a voracious appetite, talking with colleagues, and experimenting on themselves. In this manner, they have become two of the most well-informed people on the planet regarding the biochemical mechanisms of aging, and they continue to study it full- time. Pearson and Shaw then apply this knowledge in designing nutritional supplement formulations for their own use, some of which are available commercially.

Pearson and Shaw have also been very politically-active over the years with regard to protecting people’s rights in America to access nutritional supplements, and to easily obtain available accurate information about the supplements which may benefit their health. To this effect, they wrote the book Freedom of Informed Choice: FDA Versus Nutritional Supplements (Common Sense Press, 1993), and won a landmark lawsuit against the FDA–Pearson v. Shalala–charging the government agency with unconstitutionally restricting manufacturers from distributing truthful health information (which was viewed as a violation of the constitution’s First Amendment guarantee of free speech) that could save many people’s lives. This was a landmark achievement for the dietary supplement industry and for the availability of truthful scientific information to consumers.

This interview occurred on December 16, 2005. Durk and Sandy are responsible for inspiring my own interest in life extension and they have long fascinated me. The couple makes a great team, often completing one another’s sentences, and bouncing ideas and facts back and forth off each other as they speak. It’s as though their nervous systems are symbiotically intertwined, and the breadth of their knowledge is staggering. It doesn’t take much to get them talking passionately about their favorite subjects–life extension and freedom. A few questions can ignite an information explosion. We spoke about how fish oil can improve cardiovascular health, about how the FDA tried to suppress this information, and how they legally forced the FDA into reversing their unconstitutional attempt to suppress the distribution of truthful information.

David: What do you think are the most important nutritional supplements that people should be taking?

Durk: Let me just preface my answer to this question by stating that we’re dealing with a system here–a system for handling free radicals and for doing a lot of other things–and just saying, here’s the most important three or four nutritional supplements really does a disservice to people. This is because free radicals are in fact handled by a rather elaborate system that’s evolved over the past few billion years that the planet’s had oxygen, and just having one of them doesn’t really do you anywhere as much good as having a set of them. But If I wanted to mention just one, I would say EPA and DHA, particularly DHA found in oils from cold water fatty fishes. The reason for that is that it can reduce the risk of a sudden-death heart attack by anywhere from about fifty percent to eighty percent, depending on the dose. As little as two meals per week of fatty cold water fish could give you about a forty to fifty percent reduction on your risk of sudden-death heart attacks.

Sandy: Three hundred thousand people die of sudden death heart attacks every year in the United States, so if all of those people were taking the recommended amounts of fish oil supplements, or the two fatty fish meals a week, then there’d be about fifty percent fewer that would have died. In other words, a hundred and fifty thousand people would not have died.

healthOrHospitalDurk: They’re very inexpensive, very safe, and very effective. You see these sort of heart attacks on TV all the time. Somebody has a heart attack, the ambulance arrives, and they defibrillate and resuscitate the person and everything is okay. Well, it doesn’t work that way outside the hospital, because they have to get that defibrillator to the person within a few minutes.

Sandy: But most of the incidences of fibrillation occur outside of a hospital, usually in a person’s home or where they work, and they don’t get to the hospital right away. If you lose several minutes, by that time you’ve either already died or you’ve suffered irreversible brain damage, so if you do survive you’re in very damaged condition.

Durk: Under the usual conditions, your brain starts dying after about five minutes from a lack of circulation, which occurs when your heart fibrillates–just vibrates and stops pumping blood. Incidentally, that’s what happens when you are electrocuted. At about ten minutes your brain is irreversibly and completely gone. A response time for a really good paramedic operation is about eight minutes. So you can see that there’s not much of chance for revival, and in fact, paramedics in the field are actually able to revive about two percent of people whose hearts have gone into fibrillation from a sudden-death heart attack. The DHA is very effective in preventing this from occurring. It doesn’t stop the heart attack from happening, but it turns a sudden-death heart attack, which gives you very little chance, into a…

Sandy: …survivable heart attack, where you do recover, and you don’t have irreversible damage to the brain. You can have a full recovery.

Durk: They can get you to the hospital, and then they can do angioplasty, or put in a standard, quadruple bypass or whatever.

One thing that’s very important for people to know about this is that the FDA tried to suppress this information…

Sandy: …about the benefits of fish oil. We actually sued the FDA in 1994 because they would not permit a health claim that fish oils may reduce the risk of cardiovascular disease.

Durk: It’s not that they merely would not permit it; they actually issued a regulation that stated that it was a crime to state that the cold water fish oils, with omega-3 fatty acids, could reduce the risk of cardiovascular disease. It was actually illegal. They specifically made it illegal.

Sandy: So we filed suit for violation of the First Amendment, because they were not permitting the communication of truthful information.

Durk: At the time we filed suit against them in 1994 there were one hundred and seventy-four papers on the subject in the scientific literature. A hundred and seventy of them supported our position; four did not. The four that did not were very small preliminary studies that didn’t have the statistical power to detect the fifty percent reduction in sudden-death heart attacks. During the seven years that we litigated against the FDA, one million Americans died premature preventable deaths.

Sandy: Half of the three hundred thousand people dying every year from that wouldn’t have died if they’d have been taking fish oil. However, dietary supplement companies, and also food companies offering fish, couldn’t tell people about the salmon-heart-benefits of fish oil. And because of that people simply didn’t have the information.

Durk: Since the legal case was resolved in our favor in 2001, you’re now starting to see claims on fish oil supplements, and recently the FDA even caved in and is allowing claims on fish. So I think we’re going to see a very dramatic reduction in people dying of heart attacks as a result of this.

Sandy: I wanted to add that one of the ways that we study the effects of the various supplements is to look at metabolic pathway charts. You see, what happens with free radicals is that they’re handled by a chain of antioxidants in the body. It’s not just one or a couple that take care of the free radicals that are constantly around in the body. They’re constantly there because you’re producing them naturally through metabolic activity, and your body has got to handle these free radicals.

The metabolic pathways show you that once a free radical scavenger like vitamin C reacts with a free radical, then it becomes a free radical itself. It becomes an ascorbyl radical. That radical then has to be taken care of by another antioxidant. Glutathione usually takes care of the vitamin C radical, and converts vitamin C back to its reduced state.

Information obtained from http://mavericksofthemind.com/durk-pearson-and-sandy-shaw-2

Information provided for education use only. Not intended to diagnose, treat or cure any medical condition.

To Your Health! Life Priority Inc.