The Theories of Aging
The desire to fight aging has a long history, and for good reasons. Aging is the main risk factor for many chronic degenerative diseases and cancer. It causes muscle and bone loss, brain atrophy, Alzheimer’s Disease, heart disease, dementia, diabetes, and more. The signs are clear: aging is a massive risk to our health, but the exact cause of this process is still up for debate.

The theories of aging include:

1. Senescence
Increased senescent cell load in the body’s tissues is a major contributor to aging and age-related diseases. Senescent cells are those which have reached their maximum capacity to replicate. Although these cells are non-functioning, their presence in the body can cause inflammation and expedite degenerative processes in our tissues.

Recently, a new class of drugs named “senolytics†were demonstrated to extend health span, reduce frailty and improve stem cell function in multiple murine models of aging (PMID: 28871086).

Senolytics are agents that remove senescent cells, thus stopping tissue degeneration and aging complications. This allows tissues to regenerate, leading to the prevention, reversal, or delaying of age-related diseases.

Over the last few years, many senolytic agents have been identified and tested on lab animals. There are ongoing human trials involving Metformin, Resveratrol, FOXO4-related peptides, a combination of dasatinib (chemotherapy agent to treat leukemia) and quercetin, Azithromycin and Roxithromycin, HSP90 inhibitors, navitoclax and TW-37, Fisetin (a natural polyphenol found in seaweed and strawberries), and piperlongumine (an extract of long pepper root), to name a few. Scientists are also currently developing safer, non-toxic chemotherapy-based agents that act as senolytics, including Rapamycin, Navitoclax and Dasatinib (PMID: 30006159). These have all shown potential to selectively kill senescent cells and decrease oxidative stress, and some are readily available to the public over the counter or through prescription.

If these ongoing clinical trials prove the effectiveness of senolytic agents, they could bring hope to the wide range of patients suffering from severe, debilitating age-related diseases.


2. Cell division and Telomere lengths:

A popular theory of how aging progresses involves the body’s telomeres, suggesting that the shortening of telomere length over the cycle of lifelong cell division causes the body to slow its regenerative processes and lead to aging. Although this theory of aging was remarkably popular when first introduced, its validity is debatable.

Our cells contain a wide variety of telomere lengths naturally, and recent evidence has revealed that the correlation between telomere length and age-related complications in individuals is low (Müezzinler et al., 2013; Breitling et al., 2016; Marioni et al., 2016). This has led investigators to continue searching for other biomarkers that can be used in the prediction of age-related diseases with higher accuracy.

The pill TA65, derived from chinese astragalus, was promoted as a method of stopping the shortening of telomere length and expanding life span, despite the fact that its effects were only studied in 6 patients. In the field of aging treatments, hyped-up medicines with little to no proven results are all too common.

Despite the faults in this theory, telomere length may still be related to aging, even if not the direct cause. The process of aging results in multiple changes at both the molecular and cellular levels, including cellular senescence, telomere attrition, and epigenetic alterations (Lopezotin et al., 2013). Among these hallmarks, telomere length is a remarkable characteristic of aging and linked with age-related health status (Rizvi et al., 2015). The rate of shortening rather than the absolute telomere length may be a better predictor when it comes to connecting telomeres to the aging process. (Aging 2018, 10, 3397–3420)

3. Other Theories

Cellular damage has been the target of aging research for years, producing plenty of theories with varying levels of validity. For example, reactive oxygen species (ROS) are DNA damaging molecules shown to be widely linked to aging. Mutations in proteins that participate in free radical detoxification can also affect variation in aging and life span.

As for genetic causes, the list is lengthy and complicated. There are 6 genetic diseases with identified genes involved in the accelerated aging process, each currently used by scientists to study the genetic aspect of aging. There are many genes identified as the genes of aging itself, and in order to make this article as simple as possible, we will avoid going into details in that regard.

These are only a small sample of the many theories on how aging progresses, but they all have the potential to propel the science of disease prevention to new heights if given plenty of research and review.

How to Measure Aging:

There are two ways to measure aging, the first being a person’s chronological age, which is based on the date of birth. The second is referred to as biological age, which is the actual functionality and youthfulness of the body regardless of chronological age.

Currently, the best measure of biological age is DNA methylation. Anyone can check their own methylated DNA by simply sending a buccal swab to qualified labs like Cygenia in Germany or Chronomics in London. Having this information can help individuals take personalized measures to ensure their health and longevity, including lifestyle changes and the use of certain supplements or medications.

Variables in the Speed of Aging:

Although the definitive cause of aging is up for debate, there are certain factors that have been proven to slow or accelerate the process.

Cigarette smoking is observed to strongly drive mortality-associated predictive DNA methylation changes, alongside other health risks it causes. Drinking has been shown to affect methylation in a similar manner.

Calorie restriction has been proven to slow the process of aging in numerous studies. Another study showed that a vitamin and antioxidant rich diet can promote methylation of DNA in type II Diabetes Mellitus.

Those in middle age are likely to experience accelerated methylation change, although men are at higher risk than women.

No matter your current age or lifestyle, understanding aging and its potential causes can help make decisions for lifelong wellbeing. For the curious and health-conscious reader, all potential agents currently available to slow the aging process will be listed and discussed in the next article of this series.

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