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.
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.
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.
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
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