News EP 24: C-19, Caffeine, Positivity and Memory Decline, and Organ-on-chip

Covid-19 cases are steadily rising in the US and there is an aim for another lockdown. Evidence is showing that a more positive outlook on life and feeling happy in general is being associated with less memory decline.

The benefits of caffeine have been debated for years, most recently caffeine intake is being linked with long-term memory benefits. Organ-on-chip has the potential to transform the way we do research on human cells with the potential of benefiting reperfusion therapy.

Global Cases

As of 11/15 – Cases: 54,817,231 Deaths: 1,324,461

US: 11,366,503 Deaths: 251,836 Recovered: 6,935,630

  1. Texas – 1,093,645
  2. California – 1,033,687
  3. Florida – 885,201
  4. New York – 597,394
  5. Illinois – 573,616

Positivity Is Associated With Less Memory Decline: Evidence From a 9-Year Longitudinal Study

A new study finds that people who feel enthusiastic and cheerful — what psychologists call ‘positive affect’ — are less likely to experience memory decline as they age [1]. This result adds to a growing body of research on the positive effect’s role in healthy aging.

Unfortunately, we wish some memorization could last a lifetime, but emotional factors can negatively impact our ability to remember information throughout life.  

A team of researchers analyzed data from 991 middle-aged and older U.S. adults who participated in a national study conducted at three time periods: between 1995 and 1996, 2004 and 2006, and 2013 and 2014.

In each assessment, participants reported on a range of positive emotions they had experienced during the past 30 days. In the final two assessments, participants also completed tests of memory performance. These tests consisted of recalling words immediately after their presentation and again 15 minutes later.


Results revealed that positive affect was associated with less memory decline across 9 years when analyses controlled for age, gender, education, depression, negative affect, and extraversion (state of primarily obtaining gratification from outside oneself.)

What’s interesting is as people get older, they experience fewer negative emotions. Older adults are more emotionally gratifying memory distortion for past choices.

This is a broad statement but the positivity effect in older adults’ memories seems to be due to their greater focus on emotion regulation secondary to cognitive control mechanisms that enhance positive and diminish negative information. 


80% of the population consumes some type of caffeine, in the US it’s at about 90%. Caffeine is a natural stimulant most commonly found in tea, coffee, and cacao plants. It works by stimulating the brain and central nervous system, helping you stay alert and prevent the onset of tiredness.

Caffeine vs Adenosine

To understand the function of caffeine one has to grasp the concept of another neurotransmitter called adenosine. 

Most people initially drink caffeine in the form of a beverage. It’s absorbed in the small intestines within an hour and becomes available throughout the blood and most parts of the body, including your brain. The mean half-life of caffeine is about 5 hrs. As it starts entering your brain, it starts competing with adenosine.

How Adenosine Makes You Feel Sleepy

There are many different receptors in your brain, different ones have different effects. The one we’re interested in is the A1 receptor. Adenosine locks with the A1 receptor, it promotes muscle relaxation and sleepiness, which is why people get tired as the day progresses.

Furthermore, adenosine can bind to the A2A receptor. This binding interferes with the release of mood-improving neurotransmitters, such as dopamine.

Adenosine itself is produced primarily from physical work and intensive brain use. That is why over the course of the day your body accumulates adenosine.

The caffeine in your brain is competing with adenosine and preventing it from binding to A1 receptors. This is why it promotes wakefulness.

Caffeine doesn’t actually lock in with the A1 receptor. It’s more like something that gets in the way and occupies the lock, rather than actually unlocking it.

It similarly gets in the way of the A2A receptor, which can help promote the release of dopamine and glutamate, making you feel good after a cup of coffee.

Before Caffeine

When you first wake up, your body has metabolized away the adenosine molecules. You’re a bit groggy, but you’re waking up.

Effects of Caffeine

  • Stimulates your central nervous system, which can make you feel more awake and give you a boost of energy
  • Is a diuretic, meaning that it helps your body get rid of extra salt and water by urinating more
  • Increases the release of acid in your stomach, sometimes leading to an upset stomach or heartburn
    • May interfere with the absorption of calcium in the body

How much Caffeine 

  • 1 cup of coffee = 100 mg
  • 1 cup of tea = 50 mg
  • 1 can/ 12 fl oz red bull = 112 mg
  • 1 can/ 16fl oz monster = 160 mg
  • 1can/ 16 fl oz bang = 300 mg

Interesting Studies

  • This study investigated the within‐person relationship between caffeine intake and sleep duration at home.
  • 377 participants (aged 35–85 years) completed a 7‐day diary study.
  • Results revealed a significant effect of sleep duration on the change tendency of caffeine use: a shorter sleep duration predicted a stronger tendency to consume caffeine, and this phenomenon was only found in middle-aged adults (aged 35–55 years) not in older adults (aged 55+) [2].
  • This study measured the effects of 0, 12.5, 25, 50, and 100 mg caffeine on cognitive performance, mood, and thirst in adults with low and moderate to high habitual caffeine intakes [3].
  • All doses of caffeine significantly affected cognitive performance, and the dose-response relationships for these effects were rather flat. 
  • The effects on performance were more marked in individuals with a higher level of habitual caffeine intake, whereas caffeine increased thirst only in low caffeine consumers. 
  • Conclusions: After overnight caffeine abstinence, caffeine can significantly affect cognitive performance, mood, and thirst at doses within and even lower than the range of amounts of caffeine contained in a single serving of popular caffeine-containing drinks. Regular caffeine consumers appear to show substantial tolerance to the thirst-increasing but not to the performance and mood effects of caffeine.
  • A group of 1875 healthy adults, stratified for age (range 24 – 81 years), sex, and general ability, were screened for the habitual intake of coffee and tea and took part in extensive cognitive testing [4].
  • Multiple regression analysis with control for age, sex, socio‐demographic variables, and substance use showed that habitual caffeine consumption was significantly related to better long‐term memory performance and faster locomotor speed. 
  • No relationships were found between habitual caffeine consumption and short-term memory, information processing, planning, and attention as measured with the Stroop Test. Moreover, no difference in sensitivity to caffeine intake between different age groups was found, suggesting that caffeine intake did not counteract age-related cognitive decline.

Reviving Cells After a Heart Attack

Researchers have unraveled potential mechanisms behind the healing power of extracellular vesicles and demonstrated their capacity to not only revive cells after a heart attack but keep cells functioning while deprived of oxygen during a heart attack [5].

The researchers demonstrated this functionality in human tissue using a heart-on-a-chip with embedded sensors that continuously tracked the contractions of the tissue.

Extracellular Vesicles

  • Extracellular Vesicles (EVs) are nanometer-sized messengers that travel between cells known as intercellular communication.
  • EVs are a promising tool for the next generation of therapies for everything from autoimmune and neurodegenerative disease to cancer and tissue injury. 
  • EVs derived from stem cells have already been shown to help heart cells recover after a heart attack, but exactly how they help and whether the beneficial effect is specific to EVs derived from stem cells has remained a mystery.

Researchers from the Harvard School of Engineering and Applied sciences have unraveled a potential mechanism that demonstrated the potential mechanism behind the healing power of EVs.

It demonstrated their capacity to not only revive cells after a heart attack but keep cells functioning while deprived of oxygen during a heart attack. 

How was this discovered? Researchers used a heart-on-a-chip with embedded sensors that continuously tracked the contractions of the tissue.

The team tested the effect of Endothelial-derived EV’s (EEVs) on human heart tissue using the heart-on-a-chip model. Organ-on-chip platforms mimic the structure and function of native tissue and allow researchers to observe, in real-time, the effects of injuries and treatments in human tissue.

Reperfusion Injury Mechanism 

The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and oxidative damage through the induction of oxidative stress rather than (or along with) restoration of normal function.

The ischemic tissue produces more reactive oxygen species but less nitric oxide following reperfusion and the imbalance results in an inflammatory response. 

Findings in the research study 

  • The researchers simulated a myocardial infarction and reoxygenation on chips that were infused with EEVs and those that were not. 
  • They found that in tissues treated with EEVs, the cardiomyocytes could better adapt to stress conditions and sustain a higher workload. 
  • The researchers induced injury by three hours of oxygen restrictions followed by 90 minutes of reoxygenation and then measured the fraction of dead cells and the contractile force of the tissue. 
  • The heart tissue treated with EEVs had half as many dead cells and had a contractile force four times higher than the untreated tissue after injury.

What will be the future of Exosomal cell therapies?

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