Categories
Biomedical Research

Brain Transplants: Aye or Nay?

By Melle Hsing

Published 7:40 PM EST, Mon July 26, 2021

Introduction

The idea that an entire brain could be transplanted into another person remains a very controversial topic in the medical sciences. Although there has historically been no record of an entire brain transplant (also known as a head transplant) into a living human unlike what is depicted in some films, there has already been an allegedly successful human brain transplant between two human corpses in 2017. A team of surgeons have even claimed to perform an estimated 1,000 head transplants on mice! Hence, human brain transplants may just be possible, although still highly unlikely in the near future. In what situations would they be considered, and what is the controversy behind transplanting a human brain? These are some of the questions which I will explore, through three considerations: the difficulties of the procedure, the possible benefits, and of course, the ethical implications.

The Difficulties and Risks of a Brain Transplant

First of all, it should be established that a brain transplant would be extremely difficult to perform. The reason for this is that transplanting an organ from one donor to a patient should be done only when both parties are immunologically compatible with each other. This concept of “immune compatibility” is an essential consideration when transplanting a heart, liver, or kidney to another patient. As long as there isn’t an immune response in light of a foreign organ in the patient’s body, the patient should be fine. Doctors identify immune compatibility based on the similarity of genes of the human leukocyte antigens and major histocompatibility complex, which are both involved in triggering an immune response. After, immune-suppressors are injected to ensure that an immune response really won’t occur during and after the transplant. However, scientists are not very familiar with antigens located on neurons and other glial cells which poses a huge risk on patients that want to get a brain transplant.

Another factor to consider is that the brain is highly sensitive to changes in the environment, and neurons can readily die because of lack of oxygen during the transplant. In order for a brain transplant to successfully occur, the surgical room environment must be highly controlled, specifically accommodating the needs of a living brain exposed to the open air. Furthermore, the surgeons performing the transplant would need to be very careful when reconnecting the blood vessels between the implanted brain and the patient’s peripheral nervous system. They would also need to be wary of connecting the spinal cord to the brain.

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Figure 1: Surgical Operation, sourced from Verywell Mind

Why Carry Out a Brain Transplant?

According to Dr. Sergio Canavero, an Italian neuroscientist, head transplants would be used on untreatable neurological disorders that cause significant harm to the patient (e.g. muscle-wasting). On the other hand, head transplants may also be used when a patient has an unhealthy body that is beyond repair or management (essentially inhabitable) but an otherwise perfectly functional brain, in order to give them another chance at life. There are many problems with this though, and one of them is the fact that a healthy and uninhabited body is needed in preparation for the operation (which, as one could imagine, entails several ethical considerations in itself). Furthermore, there is the question of whether a person’s soul can be preserved once a transplant has been done – as in their personality and memories.

Therefore, with the large area of uncertainty towards the effectiveness of a brain transplant, brain transplants seem like a possibility that shouldn’t be taken just yet. 

Ethical Implications of Brain Transplants

There are lots of ethical considerations made for brain transplants. Firstly, there is the ethical consideration of consent, which may entail asking questions such as “who is going to donate a healthy body for a terminally ill patient with an otherwise healthy brain?” or “how does the patient feel about getting a brain transplant?”. These questions are key to answer before a brain transplant can even be performed, however they are also difficult both on the doctor’s and patient’s part to answer. The patient would have to be aware of all possible risks in going through with the operation (which could be a myriad of things), and would have to really consider what life would be like given a successful brain transplant.

The possibility of life after a brain transplant may be a scary thought, especially given that there is no telling whether the patient’s “soul” would still exist in a new body. After all, are an individual’s personality, opinions, memories, and essentially every characterization about themselves localized in the mind, or does one’s body also pose a significant influence on one’s “soul”? The interconnectivity of human bodily systems and the fact that scientists may not completely understand the complexity of interactions underlying behaviour (not just in the brain but in the entire body itself) makes this a very mind-bending (if at all philosophical) question to consider. Given that research has found links between one’s mood and emotional behaviour to other bodily systems (take the gut-brain axis as an example), how much of that behaviour would be altered as a result of such a risky operation? If other bodily systems do influence behaviour, then that would imply that the patient would exhibit different behaviours than before surgery due to being in a foreign body of differing chemical composition and stature. Hence, doctors may have to consider more than just immune compatibility when planning a brain transplant. The amount of research needed to clarify the uncertainties present in doing a brain transplant is therefore profound, such that there is very little chance for a brain transplant to actually happen in the near future. 

Conclusion

The brain, while known to be the most complex object we’ve ever known in the observable universe, is also a very fragile organ which must be dealt with utmost care. The prospect of brain transplants leaves for very interesting philosophical discussions about soul preservation and human behaviour, while it also uncovers how much humans don’t yet know about the human body and behaviour. However, it is precisely because there is so much that society doesn’t know about the human body yet and what could happen after an operation that this operation seems highly unlikely to be carried out soon.

Melle Hsing, Youth Medical Journal 2021

References

Appleton J. (2018). The gut-brain axis: Influence of microbiota on mood and mental health. Integrative medicine (Encinitas, Calif.), 17(4), 28–32.

BBC News. (2021, May 29). The brain is the ‘most complex thing in the universe’. BBC News. https://www.bbc.com/news/uk-scotland-18233409

Earth, R. (n.d.). [A surgical operation]. Verywell Mind. https://www.verywellhealth.com/head-transplant-4801452

Kirkey, S. (2017, November 17). World’s first human head transplant successfully performed on a corpse, scientists say. National Post. https://nationalpost.com/health/worlds-first-human-head-transplant-successfully-performed-on-a-corpse-scientists-say

Tay, A. (2017, July 11). Brain transplants – are they possible? NeuWrite West. http://www.neuwritewest.org/blog/brain-transplants-are-they-possibleWhiteman, H. (2015, October 15). The first human head transplant: ‘It will be a success’. Medical News Today. https://www.medicalnewstoday.com/articles/301073

Categories
Neuroscience

An Evolutionary Explanation of Loneliness

By Melle Hsing

Published 1:38 PM EST, Wed June 16, 2021

Introduction

There is the saying that loneliness has the same impact as smoking 15 cigarettes a day, which may not be an exaggeration in reality. Loneliness is the feeling of isolation, more specifically the unpleasant awareness that one is isolated. Although there is no formal diagnosis for chronic loneliness, it can pose serious threats to mental and physical health: including hypertension, depression, Alzheimer’s disease, and more. During the pandemic where large social gatherings are not encouraged, it is arguably unsurprising that there would be higher risk of chronic loneliness in individuals around the world. The negative health effects of loneliness are more dire in the elderly population, who may already suffer from loneliness due to being far away from family members in modern times. This article explores the evolution of loneliness and how it manifests in individuals, as well as what can be done to alleviate loneliness and its associated health risks.

Cacciopo’s Evolutionary Theory of Loneliness

A key difference between being alone and lonely is that the former is objective while the latter is not. Even when alone, a person may not feel lonely and when surrounded by people, one can feel lonely. Surprisingly, loneliness has evolved as a feeling to benefit human survival. According to Cacciopo’s Evolutionary Theory of Loneliness (ETL), loneliness not only induces depressed feelings, but it also acts as a warning that one’s social connections to other human beings may be prone to breaking. Humans are social animals by nature, and that renders us more favourable of forming groups to increase our chances of survival. To overcome feelings of loneliness, one is encouraged to reach out to others. Hence, from an evolutionary perspective loneliness is actually a beneficial signal which motivates individuals to reform social connections in order to stop the detrimental feelings of loneliness from physically harming one’s own body.

In a study done by Cacciopo and other researchers in 2009, lonely participants and non-lonely participants were asked to observe unpleasant pictures of people and objects. Meanwhile, researchers recorded the activation of the temporo-parietal junction (TPJ), a part of the brain which — according to scientists — handles mind tasks involving putting oneself in someone else’s shoes. The researchers hypothesized that the cause of loneliness is due to a self-protecting mechanism, which tells an individual that they need to take care of themselves before interacting with others under unfavourable or risky circumstances, resulting in social isolation. The study showed that non-lonely participants had higher activation of the TPJ and thus more inclination to put themselves in the perspective of others. On the other hand, lonely participants had lower activation of TPJ which links to the idea that lonely participants prioritise their own needs over those of others.

The temporoparietal junction (TPJ) – Brian's Bewildering Brain Blog

Figure 1: Temporo Parietal Junction (red) in the Brain, sourced from Brian’s Bewildering Brain Blog

Hence, the cause of loneliness supposedly ensures survival under certain circumstances where one’s own risk outweighs the need to prioritise the group, while loneliness itself is also a way of ensuring survival under socially favourable circumstances. 

Loneliness is also a heritable trait. A large twin study published in 2005 found that genetics contributed to 48% of the causes of loneliness, which confirms the results from a previous one-year study which investigated how loneliness was passed down as a trait. Nonetheless, it is important to keep in mind that environmental factors also influence the susceptibility to chronic loneliness and that genetics is not a defining factor of whether a person will feel chronic loneliness or not.

Chronic Loneliness in
Modern Times

There are many symptoms of loneliness ranging from loss of concentration to increased desires for engaging in certain activities such as eating, binge-watching videos, or shopping excessively. Although the proposed evolutionary explanation for loneliness may no longer apply as effectively in modern times as in the past, the same survival mechanism can still be seen throughout the modern lifestyle. For example, working from home has become more common ever since the COVID-19 social restrictions, and as a result more people are becoming isolated in their homes. Loneliness therefore warns oneself about the lack of social interaction in light of the pandemic, encouraging individuals to reach out to each other despite this being counterproductive in terms of pandemic control.

As stated earlier, there is no official clinical diagnosis for chronic illness. However, there are still many preventive measures and lifestyle changes that can be implemented to alleviate the negative impacts of chronic loneliness. Making use of social media apps such as Whatsapp, Facebook, and Skype could be beneficial for connecting with others without having to physically meet them under unprecedented times. Additionally, learning to do something new such as painting or dancing, volunteering in a community event, or simply taking a walk outside in nature can help relieve one’s own mental state. Changing one’s mindset to be more open to others and also polishing up on social skills are two methods which have shown to be effective in improving symptoms of loneliness.

Melle Hsing, Youth Medical Journal 2021

References

Cacioppo, John T et al. “Evolutionary Mechanisms For Loneliness.” Cognition & Emotion vol. 28,1 (2014): 3-21. doi:10.1080/02699931.2013.837379.

“How Loneliness Can Make You Sick.” American Psychological Association, http://www.apa.org/science/about/psa/2017/09/loneliness-sick.

“Loneliness during Coronavirus.” Mental Health UK, http://www.mentalhealth.org.uk/coronavirus/loneliness-during-coronavirus.

Raypole, Crystal. “Is Chronic Loneliness Real?” Healthline, http://www.healthline.com/health/mental-health/chronic-loneliness#when-to-see-a-doctor.

“Social Isolation, Loneliness in Older People Pose Health Risks.” National Institute on Aging, 23 Apr. 2019, http://www.nia.nih.gov/news/social-isolation-loneliness-older-people-pose-health-risks#:~:text=Research%20has%20linked%20social%20isolation,Alzheimer’s%20disease%2C%20and%20even%20death.

“The Temporoparietal Junction.” brianfarishblog.wordpress.com/2015/02/05/the-temporoparietal-junction-tpj/.

Categories
Health and Disease

Anosognosia – Not Knowing What You Don’t Know

By Melle Hsing

Published 3:12 PM EST, Sat April 3, 2021

Introduction

Patients may respond differently to news about their health — with sadness, shock, anger, relief, and more. In some cases, patients do not know how to respond, not because of denial but the lack of self-awareness in noticing  a problem. This condition is called anosognosia, which refers to the failure of an individual to recognise that they have a disorder or mental illness. Someone not knowing that they have anosognosia is in and of itself anosognosia. They may say phrases such as “there’s nothing wrong with me!” or “I don’t need your help”. With a lack of insight, a patient may refuse to get a proper medical check-up or receive crucial treatment for their illness. This article raises awareness of anosognosia as a real mental condition and  the causes and consequences of it. Undoubtedly, anosognosia also highlights the importance of a doctor’s insight.

Causes and Consequences

How does anosognosia differ from when the patient doesn’t know about the existence of their disease simply because the symptoms are hard to observe in real life? Well, patients with this condition may still believe that nothing is wrong with them even when there is strong evidence of a diagnosis, stemming from the  structural changes in their brain. The presentation of a medical condition differs from person to person, and hence the symptoms of anosognosia can manifest in various ways depending on the individual. Some may feel anger when others tell them that something they disagree with, while others may shrug off opinions. There are also those who acknowledge that they have a disease or illness one day, and refuse to believe they have it in the next. Being able to differentiate between ignorance and real disbelief is one of the challenging parts of diagnosing anosognosia.

Not all researchers agree with each other when talking about the influence of demographics on the occurrence of anosognosia. Since patients lack awareness of their illness, this means that anosognosia can only be present by definition in those with health problems, in particular, mental illnesses. Is there a biological link between a particular mental illness and anosognosia? 

According to the National Alliance on Mental Illness, 60% of schizophrenic patients do not believe that they have schizophrenia. There have also been cases where patients with bipolar disorder, Huntington’s, Alzheimer’s, Parkinson’s, and traumatic brain injury lack insight to their health issues. Studies involving patients with schizophrenia have given researchers insight to the possible biological causes of anosognosia in the brain. Self-awareness is localised in many parts of the brain in a broad network, particularly anatomical structures in the frontal lobes and parietal lobes, hence anosognosia may arise from deficient activation in these areas.

Serious Mental Illness and Anosognosia - Treatment Advocacy Center

Figure 1: Differences in brain activation between patients with low insight and high insight. Sourced from the Treatment Advocacy Center (Brain scans).

Anosognosia is the main reason why patients with schizophrenia and bipolar disorder refuse treatment. Hence, support from family members, friends, and healthcare professionals is very important to the benefit of the patient’s health.

The Doctor’s Insight

As Oliver Sacks once said, “it is singularly difficult, for even the most sensitive observer, to picture the inner state, the ‘situation’ of such patients, for this is almost unimaginably remote from anything he himself has ever known.” Empathy plays an integral role in doctor-patient communication because patients with anosognosia may feel genuinely confused, misunderstood, and even discriminated against due to the conflicting views about their own health. Hence, doctors need to think about how a patient feels, and take the patient’s opinions into serious consideration. The doctor’s response to information disclosed by a patient could influence the patient’s perception about the doctor, the doctor-patient relationship, and their trust in the healthcare team.

Patient autonomy is an extremely important aspect of professional medical practice, whereby doctors should respect the patient’s rights and decisions about their own care and treatment. When deciding on a treatment plan for any disease, doctors need to assess the mental capacity of a patient beforehand to see whether they are suitable for making such decisions. Assessing mental capacity is all the more important for patients with anosognosia. As discussed previously, patients with anosognosia may refuse any treatment or care because they believe that nothing is wrong with them, when in reality something is definitely wrong. Even if a doctor deems the patient’s decision to be unwise, he or she must still respect the decision made. Dealing with anosognosia is tricky. 

To resolve this problem, doctors usually engage the patient in self-evaluation about their own health using interviews or questionnaires to assess the presence of anosognosia. This process may be more complicated when anosognosia is prevalent in certain impairments such as motor impairment, because of the possibility that the patient has either explicit or implicit anosognosia.

Conclusion

While anosognosia may not seem like an immediate harm to the patient’s health, it can very well mislead doctors, family members, and the patient themselves to different conclusions about the patient’s condition and clinical needs. Therefore, understanding this condition is helpful for avoiding detrimental errors in clinical practice.

Melle Hsing, Youth Medical Journal 2021

References

“Anosognosia.” American Psychological Association, dictionary.apa.org/anosognosia. Accessed 7 Mar. 2021.

“Anosognosia.” National Alliance on Mental Illness, http://www.nami.org/About-Mental-Illness/Common-with-Mental-Illness/Anosognosia. Accessed 7 Mar. 2021.

Brain scans of schizophrenic patients with low insight and high insight. Treatment Advocacy Center, June 2016, http://www.treatmentadvocacycenter.org/key-issues/anosognosia/3628-serious-mental-illness-and-anosognosia. Accessed 26 Mar. 2021.

Cocchini, Gianna & Beschin, Nicoletta & Sala, Sergio. (2012). “Assessing Anosognosia: A Critical Review.” Acta Neuropsychologica. doi: 10. 419-443. 10.5604/17307503.1023693. Accessed 28 Mar. 2021.

Jewell, Tim. “What Is Anosognosia?” Healthline, http://www.healthline.com/health/anosognosia#causes. Accessed 16 Mar. 2021.

“Key Issues of Anosognosia.” Treatment of Advocacy Center, http://www.treatmentadvocacycenter.org/key-issues/anosognosia. Accessed 26 Mar. 2021.

McLean, Brendan. “The Difficulty in Seeing Your Own Illness.” National Alliance on Mental Illness, azdhs.gov/documents/az-state-hospital/the-difficulty-in-seeing-your-own-illness.pdf. Accessed 16 Mar. 2021.”What Is Anosognosia?” Treatment Advocacy Center, http://www.treatmentadvocacycenter.org/storage/documents/what%20is%20anosognosia%20final.pdf. Accessed 16 Mar. 2021.

Categories
Health and Disease

Is Aging a Disease?

By Melle Hsing

Published 3:37 PM EST, Thurs February 25, 2021

Introduction

Aging is a phenomenon that everyone experiences with every millisecond that passes. Many believe that the joy of living comes with a natural cost — a slowly degrading body. After all, it is logical to think based on the second law of thermodynamics that the longer we use our bodies, the more damage we accumulate until death. This belief also stems from what is called physiological aging. While chronological aging is simply the increase in the number of living years since birth, physiological aging refers to the decline in the body’s functionality. But given the profound biomedical research on aging in recent years, extending one’s quality of life does not seem like an impossible task for the future. What if scientists could slow down or reverse physiological aging? Would significantly increasing healthspan necessarily extend maximum lifespan?

Aging as a Disease and Diseases of Aging

To view aging as a disease would be to suggest that aging is treatable. However, many gravitate towards the notion that aging is a natural process, conceptualized by the Greek physician Galen. He argued that “aging is universal” (simply put), hence it is not a disease. Bio-demographers also agree that classifying aging as a disease would unjustly reduce numerous age-related diseases (ie. hypertension, osteoporosis, dementia) down to a single vague term, consequently oversimplifying the intricate and key discrepancies between each condition. But universality does not equate to normality, nor does the term “aging” generally assume the consequences of aging. Yes, aging may be a noun that groups a variety of diseases together, however aging itself may still have several unknown causes. 

Giving aging the “disease” label holds medical significance. Doctors and biomedical researchers alike can strive for a cure for suffering elderly patients as soon as possible instead of excusing age-related diseases as inevitable parts of aging and thus only treating the symptoms but not the root causes. David Sinclair, a geneticist at the forefront of aging research, believes that this label will also influence organizations to invest in biomedical aging research. 

Just as living organisms share different functions of life, living organisms may share certain hallmarks of aging. The Cell journal lists the nine hallmarks that are especially relevant to mammals: “genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intracellular communication”. These hallmarks largely revolve around mechanisms at the molecular and cellular level of aging to infer typical observations of aging on an organismic level such as wrinkled skin and greying hair. Even with a seemingly narrow scope of aging research, scientists have formulated many theories that try to explain the hallmarks of aging, some of which have been modified or rejected. Some of these theories are described below.

Figure thumbnail gr1
Figure 1: The Nine Hallmarks of Aging

Theories of Aging and Their Implications

The free-radical theory proposed by Denham Harman states that the accumulation of oxidative cellular damage from aerobic respiration causes aging. Aerobic respiration mostly takes place in the mitochondria of eukaryotic cells under oxygen-sufficient conditions. When mitochondria synthesize ATP as an energy source for the cell, they also produce free radicals, highly reactive due to their charged nature. In moderation, free radicals can be beneficial to our immune function and signaling. At high levels, oxidative stress damages mitochondrial DNA, the whole cell, and eventually the totality of organs in the body.

While there are studies that support Harman’s idea, he only focuses on oxidative damage in this theory, failing to take  into account a variety of processes in DNA, cells, and organs that cause damage too. Instead, looking at harm done to the body as a whole may provide a better scope of explanation for the biomarkers of aging. How do organisms protect themselves against cumulative damage?

Ramazzottius varieornatus, commonly known as a tardigrade or water bear, is an example of an organism that protects its DNA from being damaged in extreme environments. Tardigrades are astoundingly resistant to lethal environments, even in outer space. They are active when exposed to water, but when they are desiccated hydroxyl radicals are produced either from the separation of water molecules or DNA exposure to radiation. This radical damages DNA under normal circumstances, but tardigrades can make a damage suppressor protein (Dsup) which may protect its DNA from the hydroxyl radicals. Their incredible ability to resist damage has allowed them to survive for more than 500 million years. If resistance to DNA damage results in a longer lifespan in tardigrades, perhaps altering the speed of physiological aging by introducing interventions for DNA protection could do the same for humans.

Image result for tardigrades under microscope
Figure 2: R. varieornatus Under a Microscope

The somatic mutation theory of aging places a large emphasis on damage but specifically to mutations of the genetic material in somatic cells. Similar to the free-radical theory, it acknowledges  that accumulated mutations lower the functionality of organs, leading to increased susceptibility of age-related diseases. Nonetheless, the body has its own methods to repair DNA using proteins external to the genome, so do those methods become faulty over time hence fail to prevent cumulative damage or do they merely repair to a small extent? If the former is true, what is causing them to go wiry?

Sinclair argues in his book “Lifespan” that aging is the result of accumulated “epigenomic noise”, known as the information theory of aging. The epigenome regulates gene expression by instructing histones in nucleosomes to coil or loosen DNA. By switching on and off certain genes, the epigenome can control cell differentiation. 

Image result for histones and dna
Figure 3: Histones and DNA in Eukaryotic Chromosomes

Environmental factors such as radiation or toxic chemicals in the air may induce DNA mutations, eventually leading to genome instability over time. The epigenome is left to re-establish genomic stability which becomes more and more difficult as mutation rate increases due to constant assaults in the environment. Eventually, the epigenome loses control over gene expression and differentiated cells lose their identity, turning into senescent cells. Cellular senescence in turn leads to diseases such as Alzheimer’s.

Logically, by restoring epigenetic regulation, an organism can build resistance to DNA damage. This idea may seem simple but application is often easier said than done. Scientists have used the information theory of aging to test the extent to which epigenetic activity can be naturally or artificially changed in order to slow down aging or even extend healthspan, with some progress in research. The discovery of key transcription factors such as sirtuins found in humans and the supplementation of nicotinamide adenine dinucleotide (NAD+) brings hope for future treatments. 

Ethical Considerations

Anti-aging research is controversial because current understanding of aging may not be the same for everyone. Some still consider aging a natural process just like Galen did, but some believe that aging is a disease like the many diseases that can be treated. 

There is also the fear that new knowledge can pull humans further away from rationality by overexerting control over what people previously thought was an inevitable part of life. But at the same time, it is arguably rational if not altruistic for people to find ways to prolong healthspan and lifespan. After all, who wouldn’t want to live a longer life of less pain? 

Another problem is the biased convenience of future treatment. Assuming that the scientific community implements anti-aging interventions to extend healthspan, who is to decide who gets the treatment? Simply letting privileged people receive treatment puts the underprivileged at a further disadvantage, creating more inequality between the rich and poor. This bioethical concern becomes even more problematic for the values of the medical community when taking the clinical needs of patients into account, irrespective of their financial situation.

Conclusion

This topic entails philosophical thought to an unsurprisingly great extent because it questions how we understand the process of living. For example, one may ask whether health is inextricably linked to death, or whether a person can pass away having lived a healthy life assuming they do not encounter accidents. Perhaps biomedical research is a test of philosophical ideas which may very well translate into tangible actions that change the course of human nature. Such is the ambitious research done in anti-aging. 

Individuals should not think that the definition of aging is set in stone, because research can contribute many surprising insights into the reality of this phenomenon especially during technological advancement. Given the studies performed by many scientists from the 90s to the 21st century and the theories that suggest causes of aging, there is strong justification for aging to be considered a disease because it may very well be treatable.

With or without research, it is important to remember that aging is relevant to every human being regardless of the scope in which it is viewed. There is no reason to think that only scientists are able to change the way individuals age when life depends on the lifestyle one chooses to live.

Melle Hsing, Youth Medical Journal 2021

References

“4.3D: Mitochondria.” LibreTexts, https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/4%3A_Cell_Structure/4.3%3A_Eukaryotic_Cells/4.3D%3A_Mitochondria.

Adam, David. “What If Aging Weren’t Inevitable, but a Curable Disease?” MIT Technology Review, 19 Aug. 2019, http://www.technologyreview.com/2019/08/19/133357/what-if-aging-werent-inevitable-but-a-curable-disease/.

Bulterijs, Sven et al. “It is time to classify biological aging as a disease.” Frontiers in genetics vol. 6 205. 18 Jun. 2015, doi:https://doi.org/10.3389/fgene.2015.00205

Clemson, Lindy, et al. “Free-Radical Theory of Aging.” Encyclopedia of Behavioral Medicine, 2013, pp. 816-17, doi:https://doi.org/10.1007/978-1-4419-1005-9_191.

Epigenetics in the Central Nervous System. http://www.researchgate.net/figure/DNA-is-wrapped-around-a-cluster-of-histone-proteins-to-form-nucleosomes-The-two-main_fig1_257806432/actions#reference.

Faragher, Richard G A. “Should we treat aging as a disease? The consequences and dangers of miscategorisation.” Frontiers in genetics vol. 6 171. 14 Jul. 2015, doi:https://doi.org/10.3389/fgene.2015.00171

“Free Radicals, Antioxidants in Disease and Health.” International Journal of Biomedical Science, vol. 4, no. 2, june 2008, pp. 89-96, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614697/.