Prolonging life and the ethical ramifications

The age-old (pun intended) quest in search of eternal life or at the very least increasing longevity has possibly truly begun.

Mitochondria have long been correlated with age-related disorders. When mitochondria reach a certain point in their “lives” they undergo a morphological change such that they transform from round and small to elongated and big. This change seems to result in loss of function, which makes sense since we know structure denotes function. Damaged mitochondria are usually degraded via a type of autophagy known as mitophagy which is specific for degradation of dysfunctional mitochondria. However, these elongated mitochondria are difficult to remove from the cell, because of their size and shape, so they tend to accumulate within the cell. This accumulation leads to cell toxicity and has been correlatively linked to age-related disorders.

Researchers at UCLA have discovered how to induce anti-aging characteristics (via promotion of healthier mitochondria) by increasing the levels of a protein that helps reduce the accumulation of dysfunctional mitochondria in cells (see image below). Typically, levels of this protein decrease with age and lead to the undesired changes in size and shape previously mentioned. Female flies lived 20% longer with this protein induction and male flies lived 12% longer than their counterparts that composed the control group. Control group flies were unable to remove damaged mitochondria efficiently after a certain age.

Images shown in a - c show the natural progression of aging mitochondria that change from small and round in youth to elongated and large in midlife (around 30 days). Image d shows the more youthful appearance of mid-aged mitochondria after protein induction (hence, anti-aging effects). Stark differences between c and d support anti-aging results since age is the same. The same results are observed with different imaging techniques, as shown in rows 2 and 3. 

Here the hope is to develop drug therapies that can mimic the actions of this protein and induce similar results (delaying onset of disorders and mortality) in humans.

If we can accomplish this and live longer, should we? Why or why not?

Maleficence – we do not know what kind of side effects could result from this type of anti-aging therapies, either to the individual or our entire society. If the potential harms could outweigh the potential benefits then this is not a road we should venture onto, which leads into justice. Who will be able to obtain access to these potential anti-aging and longevity-increasing therapies, and will this be fair to all? Typically, low SES populations will not be able to access these therapies since they will be expensive and most forms of public insurance will not cover this type of treatment.

Imagine an individual who will be the next: Albert Einstein or Barbara McClintock or Jonas Salk or Rosalind Franklin or Rosa Parks or Frida Kahlo or Amelia Earhart or Mahatma Ghandi; in other words, someone that makes accomplishments that better humankind.

This individual is unable to afford this treatment but will hopefully continue to be an outstanding contributing member of society if they had more time to do so by living longer. Society might deem this individual worthy of receiving the treatment for free (if they agreed to receiving it) or at a significantly reduced cost. However, would this opportunity be extended to another individual (same sex, age, and SES) who was a single-parent raising 3 young children who was also experiencing clear symptoms of early-onset Parkinson’s Disease?


Sources:
Rana, A., Oliveira, M.P., Khamoui, A.V., et al. Promoting Drp1-mediated mitochondrial fission in midlife prolongs healthy lifespan of Drosophila melanogaster. Nature Comm 8:448, 1-14 (2017). DOI: 10.1038/s41467-017-00525-4

Blood Flow Restriction Training: A Novel Technique to Induce Muscle Hypertrophy

Everyday, millions of people workout at gyms aspiring to build muscle and achieve their ideal physique. Their workout programs can consist many different techniques to try to cause their muscle fibers to hypertrophy, in other words causing muscle fibers to grow leading to increased muscle mass. Some classic techniques include supersetting (e.g: doing 8-12 reps of bench press then immediately doing 20 pushups without rest in between the two exercises), drop sets (e.g: doing 8-12 reps of 25lb bicep curls then doing 8-12 reps of 20lb bicep curls and then doing 8-12 reps of 15lb bicep curls), or negative reps where the user focuses on controlling the eccentric part of muscle contraction.

Figure 1. An example of biceps training using negative reps. The user concentrates on slowing down and resisting the weight during the eccentric muscle contraction. Users can handle more weight on the eccentric muscle contraction and some believe this can lead to more muscle hypertrophy.

A new technique that has come to light is blood flow restriction (BFR) training. In blood flow restriction training, a band is wrapped around your arm or leg just tight enough to restrict blood to the veins while leaving arteries open. This allows blood to rush to your muscles but decreases the rate at which it can be returned via the veins. This restriction coupled with high rep training can lead to an increase of cell swelling and lactic acid buildup which can promote protein synthesis and muscle hypertrophy. The increased cell swelling causes muscle fibers to create small tears that are repaired via protein synthesis. The result is a bigger muscle fiber. (Loenneke, Fahs, Rossow, Abe, & Bemben, 2012) If you are an adventurous person looking to build muscle, try this technique and incorporate it into your routine.

Figure 2. An example of an occlusion band applied during bicep training. The band is tight enough to block venous return, while allowing blood to freely flow through the arteries.

References:

Loenneke, J. P., Fahs, C. A., Rossow, L. M., Abe, T., & Bemben, M. G. (2012). The anabolic benefits of venous blood flow restriction training may be induced by muscle cell swelling. Medical hypotheses, 78(1), 151-154.

Enchroma: Harnessing the Power of Light

        

         If you've ever seen Little Miss Sunshine, then you’ll remember the heart-wrenching scene when Dwayne Hoover realizes to his dismay that he is color blind, and has his dream of becoming a pilot shattered. In fact, there are many jobs you can’t have if you are colorblind, such as an electrician, a firefighter or a police officer. Colorblindness is a general term that encompasses many deficiencies in a person’s ability to perceive color. There are seven different types of colorblindness, and varying degrees of each. 

Figure 1a: Percentage of the population with varying degrees of color perception.

   


          Eyes convert light into electrical impulses in the retina via two kinds of photoreceptors, rods and cones. Rods function in dim lighting, line the outer edges of the retina and are used in peripheral vision. Cones function in bright light and provide color images and sharp outline. There are over 6 million cone cells and three different types of cones named for the wavelengths of light they absorb best- red, blue and green cones.  All other colors come from a mixture of two or more of these cone cell types. Colorblindness is the abnormal function or deficiency of one or more types of cone cell. Thus, most people who are colorblind just have a reduced ability to see colors. Approximately 8% of men and 0.5% of women have some variation of colorblindness (NIH, 2015). 

 

Figure 1b: Normal absorbance of the color spectrum.

       Enchroma is a company that is trying to combat some aspects of colorblindness. Enchroma’s glasses were derived from an invention by Don McPherson- laser safety glasses for surgeons. One afternoon, McPherson was playing a game of ultimate frisbee and was wearing these surgical glasses. His friend asked to try on McPherson’s sunglasses and when his friend, who happened to be colorblind, put them on, McPherson realized the true potential of his invention (Zhou, 2015). The glasses saturated colors because they contained embedded rare earth iron that absorbed a significant amount of light, originally to keep surgeons safe and to easily differentiate between blood and tissue. McPherson teamed up with mathematician Andrew Schmeder to optimize the glasses. Schmeder designed a filter for the glasses that targets specific photopigments. Enchroma created a method called “multinotch” filtering that cuts out sharp wavelengths of light to enhance specific colors (Enchroma, 2017). The blue cones generally work independently while the red and green cones overlap to help create intermediate colors. For example, if 10 photons land on the red cones and 90 land on the green cones, the object will be perceived as more green. However, if 50 photons land on the red cone and 50 land on the green cone, then the object will be perceived as yellow. In the majority of color blind individuals their red and green cones overlap too much, distorting the perception of colors. Enchroma glasses  absorb a band of light between the exaggerated overlapping of the red and green cones, enhancing colors by making each cone more distinct. This reestablishes the normal distribution of photons on the red and green cones. Enchroma glasses are not a cure for severe colorblindness but may help with day-to-day activities, such as driving, in individuals with mild deuteranomaly. However, recent studies involving gene therapy of these cones in monkeys have proven to be successful- a cure for colorblindness may be in our future (Casagrande, 2009).

References

Casagrande, V. (2009). Faculty of 1000 evaluation for Gene therapy for red-green colour blindness in adult primates. Nature, 461, 784-787. doi:10.3410/f.1164850.626698

Enchroma. (2017). Technology. Retrieved October 25, 2017, from http://enchroma.com/technology/

NIH: National Eye Institute. (2015, February 01). Facts About Color Blindness. Retrieved October 25, 2017, from https://nei.nih.gov/health/color_blindness/facts_about

Zhou, L. (2015, March 03). A Scientist Accidentally Developed Sunglasses That Could Correct Color Blindness. Retrieved October 25, 2017, from https://www.smithsonianmag.com/innovation/scientist-accidentally-developed-sunglasses-that-could-correct-color-blindness-180954456/

Neurotransmitter Respecification

We have known for a long time that neurons have a certain unchanging specificity for the neurotransmitter they release. We have dopaminergic neurons releasing dopamine, serotonergic neurons releasing serotonin, cholinergic neurons releasing acetylcholine, and so on.

Neural plasticity is the idea that our brains can change in many different ways to adjust to physiological and behavioral changes that our bodies have. Frequently, this plasticity is expressed by a general change of pace within the neuron. This can be a varying rate of firing of action potentials, differing quantal release of neurotransmitter, or other similar changes within the cell. It was not until recently that we began to think that a cell could completely change which neurotransmitter it expressed, not just simply how much of a given neurotransmitter is released. This idea is labeled neurotransmitter respecification.
Spitzer’s fascinating research, outlined in the article linked below, found that this neuronal plasticity may go further than we had ever imagined; that neurotransmitter respecification can happen secondary to certain stimuli. Studies using primates showed that when eyelids were sutured shut, blocking visual input, the number of GABAergic neurons were reduced and later reappeared when vision was returned (opening of the eyelids). The mechanism was not that less GABA was released from those neurons, it was that those previously GABAergic neurons were no longer useful and reassigned themselves to a new neurotransmitter that would be beneficial to the system.
The potential clinical implications of this study are numerous. There are countless central nervous system diseases that result from altered levels of a neurotransmitter-take Parkinson’s Disease and dopamine for example. Parkinson’s is caused by the depletion of dopamine in a part of the substantia nigra. Current drug therapies attempt to restore some dopamine by administering the precursor, L-dopa, to a patient in order to synthesize and make up for some lost dopamine. Scientists are developing an additional type of therapy where certain stimuli can morph other neurons into dopaminergic ones to compensate for the disease-related loss. One therapy, already in use for many patients suffering from seasonal affective disorder, is the use of bright white lights, which can induce new dopaminergic neuron formation in the brain. Other disorders that this technique could targeted include Alzheimer’s and fragile X syndrome.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352171/

How Thyroid Hormones Effect HCC

Hepatocellular carcinoma or more commonly known as liver cancer, is a very prominent type of cancer and has been tied to a hypothyroidism as an indicator. However, the role of the hormones produced by the thyroid in hepatocellular carcinoma have not been extensively studied.

The levels of TSH (thyroid stimulating hormone) and fT4 were measured and then compared to the various characteristics of the cancer such as tumor size and CRP which is a way to measure the inflammation in the body. It was found that when the levels of TSH was increased, then tumor size was larger and when the levels of TSH were decreased, the size of the tumors was smaller. The patients who had a higher level of fT4 were more likely to have elevated CRP levels.

While this study was specific to just thyroid hormones and their effects on the characteristics of liver cancer, the implications of this study in the rest of oncology are huge. This tells us that the endocrine system and its products can be used as indicators of certain diseases as well as perhaps being the reason some cases are worse than others. If these hormones can be controlled then the diseases themselves might also be effected and better maintained.

Pinter, M., Haupt, L., Hucke, F., Bota, S., Bucsics, T., Trauner, M., … Sieghart, W. (2017). The impact of thyroid hormones on patients with hepatocellular carcinoma. PLoS ONE, 12(8), e0181878. http://doi.org/10.1371/journal.pone.0181878

Ibuprofen linked to poor cardiovascular health?

The use of painkillers and anti-inflammatory drugs like aspirin and ibuprofen causes change to the human HPA axis. Non-steroidal anti-inflammatory drugs (NSAIDs) were designed to reduce pain by inhibiting prostaglandins COX1 and COX2 that signal the feeling of pain. COX 2 is most often selected to be inhibited due to inhibition of COX 1 causing gastrointestinal problems. NSAIDs that inhibit COX 2 have had reports of correlation to cardiovascular problems for around the past 15 years. As of today, there is not a whole lot of information about the causal effects that NSAIDs may have on human cardiovascular health, but there is research being done on this topic.

The research done by Arfè et al. found a positive correlation between the administration of COX2 inhibiting NSAIDs and heart failure. The results of the paper show that there is a 19% increased risk of heart failure in patients currently using NSAIDs (i.e. within the last 14 days) compared to patients that did not use NSAIDs in the past 183 days. The study also suggests that because COX2 inhibition is increases with increased dosage of NSAIDs, the risk of heart failure increases with increased dosage.

            Arfè, A., Scotti, L., Varas-Lorenzo, C., Nicotra, F., Zambon, A., Kollhorst, B., & ... Corrao, G. (2016). Non-steroidal anti-inflammatory drugs and risk of heart failure in four European countries: nested case-control study. BMJ (Clinical Research Ed.), 354i4857. doi:10.1136/bmj.i4857

When Do Kids Get to Be Kids in Today’s Hectic Lifestyle?

It seems as though kids are constantly running from one activity to the next, never stopping to smell the roses and just hang out with their friends. Some may say that this is a good thing, keeps kids from getting into trouble, but could it also be harming them?

My younger sister is fifteen, and she, like most other kids her age, is constantly running from one extracurricular activity to the next. This constant running around has caused her a significant amount of psychological stress and has resulted in Amplified Musculoskeletal Pain Syndrome (AMPS).

“Amplified musculoskeletal pain syndrome (AMPS) is a very painful medical condition that can cause pain anywhere in the body…the degree of pain children with AMPS experience is more intense than one would normally experience.”(Philadelphia, 2014). In order to understand what is happening physiologically in a patient with AMPS, one should understand how pain is felt normally. Pain is triggered as a response to tissue damage. This damage then sends a signal through the pain nerve and to the spinal cord. The spinal cord transfers the signal to the brain where it is recognized as pain. In an AMPS patient, there is a short circuit in the spinal cord which causes the pain signal to not only travel to the brain but also through the autonomic nervous system. The transference of pain through this system causes the blood vessels to constrict leading to a decrease in blood flow and oxygen delivery throughout the body.  This syndrome has three major causes: injury, illness, and psychological stress.

My sister’s AMPS presents itself as chronic pain in her legs. It is caused from psychological stress, and her hectic lifestyle of running from one activity to the next makes it very difficult to deal with her syndrome.  When she was diagnosed last year, she was required to quit all extracurricular activities until the pain was able to be managed. She has to desensitize her legs four times a day and visit a  phycologist once a week to learn how to deal with the stress in order to control the pain.

References

Philadelphia, T. C. (2014, February 23). Amplified Musculoskeletal Pain Syndrome (AMPS). Retrieved October 16, 2017, from http://www.chop.edu/conditions-diseases/amplified-musculoskeletal-pain-syndrome-amps

A skin patch that dissolves fat?

Humans have two types of fat. White adipose tissue (WAT) stores excess energy in large droplets of triglycerides, typically referred to as unhealthy or "bad" fat. Brown adipose tissue (BAT) contains smaller droplets and a high number of mitochondria that burn fat to produce heat. When exposed to cold temperatures or when stimulated by exercise, the body can convert adult WAT into BAT in a process known as browning. This process can be employed to combat diabetes and obesity (Cavalera, Axling, Berger, & Holm, 2016; Khidr, Ali, Elshafey, & Fawzy, 2017; Wankhade, Shen, Yadav, & Thakali, 2016). However, current treatment options are limited to pills and injections, which are do not produce strong or localized results.

A research team at the Columbia University Medical Center (CUMC) and the University of North Carolina (UNC) wanted to investigate localized browning while increasing overall metabolism. They created a microneedle skin patch that has nanoparticles containing either rosiglitazone (Avandia), an oral diabetes medication, or CL316243, a beta adrenergic agonist (a class of medication that relaxes muscles in the airway) that has been shown to stimulate browning in mice (Zhang et al., 2017). The mice two patches which were placed on either side of the lower abdomen. The patches were replaced every three days over the course of four weeks. Experimental mice received one patch with drug-containing nanoparticles and one patch with empty nanoparticles, while control mice received two patches with empty nanoparticles.

The experiment demonstrated an additional 20% overall fat reduction on the side receiving a drug when compared to the side receiving no drugs. Treated mice exhibited lower fasting blood glucose levels than control mice. Genetic analyses also indicated an increase in BAT-associated genes when exposed to the drug, and the increase was observed locally. Applying the patch to lean mice led to an increase in oxygen consumption, indicating a metabolic increase.

However, this technology cannot quite yet be applied to humans. Humans lack beta3 andrenergic receptors in adipose tissues, meaning CL316243 may not be a viable treatment option. Furthermore, this patch only locally treats the symptoms of obesity and diabetes. For most, proper nutrition, exercise, and sleep are key to resolving obesity and managing diabetes.

References

Cavalera, M., Axling, U., Berger, K., & Holm, C. (2016). Rose hip supplementation increases

energy expenditure and induces browning of white adipose tissue. Nutrition &

Metabolism, 13, 1-9. doi:10.1186/s12986-016-0151-5

Khidr, E. G., Ali, S. S., Elshafey, M. M., & Fawzy, O. A. (2017). Association of irisin and

FNDC5 rs16835198 G > T gene polymorphism with type 2 diabetes mellitus and diabetic

nephropathy. An Egyptian pilot study. Gene, 626, 26-31. doi:10.1016/j.gene.2017.05.010

Wankhade, U. D., Shen, M., Yadav, H., & Thakali, K. M. (2016). Novel browning agents,

mechanisms, and therapeutic potentials of brown adipose tissue. Biomed Research

International, 20, 161-15. doi:10.1155/2016/2365609

Brain wave sensing headphones?

A company called Mindset is crowdfunding for a set of headphones that can apparently use EEG combined with special algorithms to detect a user's brain waves to see if they are focused, distracted or tired.  Mindset claims using these headphones will keep users from getting distracted by telling them when they are distracted; therefore, promoting better concentration.  

Here is a link to their Kickstarter page: https://www.kickstarter.com/projects/mindset/headphones

This all seemed too good to be true, so I looked into the technology and physiology a little to see if it can actually work.  

We learned how nerve impulses travel through graded potentials and action potentials.  Everything we feel, think, and do is communicated through the body and brain by neurons and their changes in membrane potential.  This means that our thoughts create a tiny change in the charge of certain areas of our brain.  This can be measured by an electroencephalogram (EEG).  One study looked at the EEG of subjects while in a driving simulation.  They found that a concentrated driver had high activity in their frontal cortex compared to lower frontal cortex activity by a distracted driver (2).  This tells us that it is possible to determine if a person is distracted or not by using EEG.  The one used in this study probably had dozens of electrodes, required a saline solution for better conductivity, and cost thousands of dollars.  The mindset headphones only have five electrodes, they apparently need no saline and costs much less. Can they still detect distraction?  

Since the Mindset product is still in development, nobody other than the Mindset company has done research to see if it really works. A study tested a similar consumer EEG device.  This device with seven dry electrodes was used to test the brain waves of a meditating monk.  The team concluded that the much simpler and cheaper device effectively recorded a signal and could potentially be used in research applications (1).  So, maybe a set of headphones with five dry electrodes could accurately record EEG data.  

If products like this work, is it something we should be worried about?  If EEG can vaguely infer our thoughts, would it be dangerous if the collected data got into the wrong hands?  Ad companies could use it to determine if we are interested in a product or not! Hopefully, the companies developing consumer EEG are creating these devices to benefit the buyer's mental health instead of using it to manipulate them for money (Justice and beneficence!)

Comment what you think! Do these headphones look like they could work? Even if they do, what steps should be taken to protect our thoughts from being "hacked" ?

References:

1. D. Surangsrirat and A. Intarapanich, "Analysis of the meditation brainwave from consumer EEG device," SoutheastCon 2015, Fort Lauderdale, FL, 2015, pp. 1-6.
doi: 10.1109/SECON.2015.7133005

2. C. T. Lin, S. A. Chen, L. W. Ko and Y. K. Wang, "EEG-based brain dynamics of driving distraction," The 2011 International Joint Conference on Neural Networks, San Jose, CA, 2011, pp. 1497-1500.

doi: 10.1109/IJCNN.2011.6033401

HIIT (High Intensity Interval Training) - Is it really worth it?

What is HIIT. High Intensity Interval Training is a form of cardiovascular exercise that involves a routine of maximum physical output followed by a less intense recovery routine. Studies have shown that HIIT increases your endurance, cardiovascular fitness and can promote healthy blood glucose levels. Is this program worth it?

HIIT has shown to increase the average person’s ability to consume oxygen (VO2 max). Generally, a higher VO2 max means better health. HIIT has also shown to decrease the risk of type 2 diabetes. Jelleyman and her associates published a meta-analysis showing that blood glucose was lowered following HIIT than continuous non-HIIT exercise. One of the biggest effects of HIIT is its ability to quickly increase muscle endurance. So, on average a person can increase muscle endurance with a shorter HIIT workout than a long endurance training workout.

Let’s review, when our nervous system sends a signal for a muscle to contract, channels open allowing calcium to leave the SR and bind to its receptor allowing myosin and actin to do its thing. For “un-athletic” guys, a single HIIT workout results in fragmentation in these channels. Now calcium slowly leaks out and this little constant release in calcium causes stress to the cell. According to this article, the cell responds to this stress by increasing their endurance, allowing them to improve. Endurance athletes do not gain the same benefits. What is the issue with HIIT?

HIIT has shown an increase in muscle endurance but not much improvement in your weight. HIIT is a hard workout and it’s psychologically tough. People must be careful, injury is a serious issue with HIIT. Many people complain that they don’t have the time to work out. Not only is HIIT tough on your body, you need to give your body enough time to recover before you partake in another HIIT workout. Your body will feel very sore and you will be in a lot of pain post exercise. You must LOVE HIIT to participate in this program with the little time you set aside for exercise.

If you are a couch potato, HIIT is a great way of reducing your fat, although you won’t see a big difference in weight. If you are okay with the long and aching recovery days, but don’t have a lot of time, then HIIT is the program for you.

https://www.sciencenews.org/blog/scicurious/high-intensity-interval-training-has-great-gains-—-and-pain