THE RACE AGAINST AGING

Figure 1: The Nine Hallmarks of Aging (L Lopez-Otin et al., 2013).

Why do we age?

There have been many proposed explanations for the causes or purpose of organismal aging. The debate over whether aging is a regulated and adaptive process or merely a pointless result of accumulated deleterious events is still ongoing (Schmeer et al., 2019). Some of those explanations suggest evolutionary reasons as to why aging exists as a phenomenon, and others propose mechanistic theories that involve specific causes at a molecular, cellular, and organismal level (Vujin & Dick, 2020). A common evolutionary view is that aging is a by-product of mutations that manage to “escape” natural selection. If an individual has already succeeded in reproducing, its genetic information will persist in the population regardless of subsequent deleterious events that may occur during aging (De Winter, 2014). A recent mechanistic theory suggested by Dr. David Sinclair and his colleagues is that the leading cause for aging is the loss of epigenetic information in cells. Dr. Sinclair proposes that loss of this information is the central reason that leads to loss of cellular identity, cellular senescence, and disease (Vujin & Dick, 2020).

Although the loss of epigenetic information most likely plays a significant role, it may not necessarily be the sole reason behind aging, as it is not mutually exclusive with other causes such as telomere attrition and loss of proteostasis. Furthermore, mechanistic explanations such as loss of epigenetic information are not mutually exclusive with evolutionary theories. Similar to the example of mutations avoiding natural selection, such deleterious mechanisms may have also “escaped” natural selection, since they usually become detrimental beyond the typical reproductive age.

Is aging a disease?

The answer to this controversial question will depend on the definition of a disease. De Winter (2014) defined disease as a condition with three characteristics:

1. A state that leads to a reduction of functionality below typical levels, either caused by internal processes or environmental factors,

2. And a reduced capacity of coping with environmental changes,

3. When compared to a sufficiently broad reference class.

With this definition, De Winter argued that aging is no less of a disease when compared to conditions commonly referred to as diseases such as diabetes. There is an evident decline of biological abilities correlated with aging, so (1) is satisfied. For (2), many physiological processes that allow the body to cope with changes in the environment decline with aging as a result of the hallmarks explained earlier, so it is satisfied as well. For (3), it is easy to choose a broad age group as a reference class; an example could be between 30 and 75. Although this may not be a widely accepted view, it should nonetheless inspire more research about the mechanisms of aging and the potential preventive steps that can be taken to slow or stop it.

Is it possible to slow, prevent, or even reverse aging?

Although the answers to these questions were not clear for a long time, people have always attempted to halt aging and prevent its consequences, mainly mortality. Alchemists of ancient civilizations attempted to craft “elixirs of life,” primarily to “cheat death.” Those elixirs seemed to have failed and sometimes even hastened the death of the consumer, as was the case with the first Chinese emperor, Qin Shi Huang Di (Vujin & Dick, 2020). However, modern science approaches the matter differently, and researchers are beginning to have a better idea about whether it is possible to cripple the mechanisms of aging or not. After all, it is not inconceivable that aging may not be inevitable, as evidenced by multiple animals and plants which do not have an age-dependent increase in mortality, also known as negligible senescence (Vujin & Dick, 2020).

It is common knowledge that regular physical exercise and a healthy diet can promote a longer and healthier life. There is also increasing evidence that caloric restriction and intermittent fasting can increase regenerative capability and reduce the risk of age-related diseases. These approaches may indeed be simple and practical ways to slow aging, but they may be difficult to implement for some, especially for people already struggling with health issues. Other solutions are being investigated as scientists study the specific biochemical mechanisms that play a role in aging. One particularly important family of enzymes involved is the family of sirtuin proteins, which seem to play a crucial role in regulating the epigenome. Other important molecules include resveratrol and the anti-diabetes drug metformin. Work on model organisms has shown that stimulation of these “longevity molecules” extends an individual’s healthspan (the period of life spent in good health) and lifespan. However, human trials have yet to show promising convincing results. (“Increasing Healthspan: Prosper and Live Long”, 2015).

Dr. Sinclair’s work on mice and his results have gained popularity as they have shown not only a promising explanation for aging but also ways to slow or even prevent it. In his book titled “Lifespan: Why We Age – and Why We Don’t Have To”, Dr. Sinclair advocates for a regimen to which he adheres himself, ranging from supplement intake to simple lifestyle changes. He believes that this regimen not only extends the lifespan of those who adopt it, but also the healthspan. Dr. Sinclair’s regimen includes typical advice such as exercise and healthy eating. However, he also suggests that the usage of certain supplements, such as NMN, may help stimulate sirtuins and increase the healthspan (Kane & Sinclair, 2019). Other supplements include resveratrol, metformin, vitamin D, vitamin K2, and aspirin. The lifestyle changes include limiting the intake of highly glycemic foods, reducing the number of meals, eating a plant-based diet, exercising regularly, avoiding toxins and radiation, exposure to cold, and maintenance of a healthy BMI (Sinclair et al., 2019).

Many of these interventions are already known to have a positive impact on the healthspan of an individual. In addition to those healthy lifestyle changes, Dr. Sinclair claims that elevated levels of epigenome maintenance, mainly by high stimulation of sirtuins through NMN intake and caloric restriction, will significantly delay or even prevent many of the diseases that commonly appear in old age and cause death (such as heart disease, diabetes, cancer, etc.) (Vujin & Dick, 2020).

It is important to note that although Dr. Sinclair’s regimen may be exciting, it involves some weaknesses in its scientific approach. Mainly hasty generalizations from studies conducted on model organisms, with insufficient human trials. This weakness and potentially others are analyzed further by Vujin & Dick (2020).

Conclusion

The average lifespan of humans has drastically improved compared to past centuries, thanks to the advances in healthcare, vaccination, and other factors (Although, the rate of increase has been slowing down (Cardona & Bishai, 2018)). It will likely continue to increase in the upcoming decades, thanks to the ongoing research and increasing understanding of the biological mechanisms behind aging. However, whether it will increase enough for Homo sapiens to eventually become “immortal” is yet to be clear, as the mechanisms of aging remain to be fully understood. Moreover, current anti-aging regimens such as that of Dr. David Sinclair may be interesting and exciting, but they lack sufficient evidence to be advised for humans and require more research.