Understand Your Aging Process: The 12 "Hallmarks of Aging"

Research on the aging process has identified 12 key processes that are referred to as "hallmarks of aging". (1) It helps to understand the hallmarks of aging if you want to prevent, counteract, or defeat them. Here they are, listed in the order they appear in a recent scientific article reporting on the updated list of aging hallmarks:

Genomic instability
Telomere attrition
Epigenetic alterations
Loss of proteostasis
Disabled macroautophagy
Deregulated nutrient-sensing
Mitochondrial dysfunction
Cellular senescence
Stem cell exhaustion
Altered intercellular communication
Chronic inflammation
Dysbiosis

Genomic Instability

DNA is the "blueprint" for most, if not all, functions of the human body. But DNA is vulnerable to damage from toxicants, ionizing radiation, oxidants, errors in replication, and other factors. The body possesses mechanisms that can repair DNA, such as a group of seven proteins called "sirtuins", but our DNA repair mechanisms typically decline as we get older. As DNA damage accumulates, cells and organs start to malfunction.

Telomere Attrition

When our cells divide to produce new cells, the DNA must also divide in order to create copies of the DNA for the two daughter cells of the division. The proteins that copy the DNA sit on the DNA strand that they copy. When these proteins reach the end of the strand of DNA, they cannot copy the part of the strand that they are sitting on, so this portion of the strand is lost. In order to prevent the loss of functional DNA, there is an "end cap" on the DNA called a telomere.

Telomeres consist of non-coding DNA that the body can afford to lose when DNA is replicated. But when the telomeres become too short, then coding DNA will also be lost when the cell divides. Once the telomeres become too short to avoid loss of functional DNA during cell division, cells stop dividing. This is the reason that human cells can typically only divide a finite number of times. This limit on the number of cell divisions is known as the "Hayflick limit".

Until recently, telomeres were thought to be the most important hallmark of aging, but it turns out that telomere length is far less indicative of biological age or predictive of lifespan than other factors, such as patterns of DNA methylation, which currently seems to be the best measure of biological age. Nevertheless, telomere attrition remains an important factor in the aging process.

Epigenetic Alterations

While DNA is the foundation code for the structure and function of our bodies, we also have a system that determines which parts of the DNA code are used at a particular time by a particular cell. The body attaches and detaches small molecules like methyl groups or acetyl groups to DNA in order to control which genes are turned off or on. The process of controlling DNA expression in this manner is called "epigenetics".

Epigenetics is also how the body directs the process of cellular differentiation so that each specialized cell type knows whether it is a brain cell or a butt cell (haha). Epigenetics is also how the body regulates its response to environmental cues like extreme heat or cold, caloric scarcity or abundance, toxicants or infectious agents, etc.

Research has demonstrated that DNA methylation patterns (one aspect of epigenetics) track very closely with chronological age, suggesting that epigenetics actually programs the aging process since we typically age in proportion to our chronological age. Long-term research on DNA methylation has also observed that people who maintain youthful patterns of DNA methylation look younger and experience less disease than people of the same chronological age who have less youthful patterns of DNA methylation. So the evidence is quite strong that epigenetic alternations are very important hallmarks of aging.

Loss of Proteostasis

Proteins execute countless essential functions in the body, including enzymatic reactions, repair functions, waste removal, most communication processes, and more. The loss of proteostasis (protein homeostatis) is a loss of the ability to maintain normal proteins and is therefore characterized by increasing amounts of dysfunctional proteins, proteins that are misfolded, misconfigured, or otherwise damaged in some way. The loss of protein function has wide-ranging effects, including oxidative stress, chronic inflammation, DNA damage, incomplete DNA repair, mitochondrial dysfunction, organ dysfunction, diabetes, dementia (e.g. Alzheimer's disease), cancer, and more.

Disabled Macroautophagy

Autophagy is the recycling of damaged cellular components and is one of the mechanisms for maintaining proteostasis (the previously described hallmark of aging). Macroautophagy is the recycling of large cellular components like organelles, which are the "organs" of the cells, the cellular "machinery" that carries out the processe of life. Mitochondria are an example of one type of organelle. By recycling damaged organelles and other cellular components, macroautophagy essentially rejuvenages cells and keeps them functioning in a youthful manner. The loss of effective autophagy accelerates aging.

Deregulated Nutrient Sensing

The body is always responding to nutrient abundance and scarcity, and it does this through a varity of "nutrient sensing" mechanisms, the most well-known of which is "mTOR" (mammalian / mechanistic target of rapamycin). Amino acids and insulin stimulate mTOR, and mTOR increases protein synthesis, metabolism of glucose and fats for energy, mitochondrial biogenesis, and other processes, while it inhibits autophagy.

Nutrient sensing can become dysregulated as we get older and by poor dietary choices (e.g. excess intake of calories and simple carbohydrates). As nutrient sensing and energy metabolism get dysregulated, degenerative diseases like cancer, diabetes, dementia, and heart disease develop.

Mitochondrial Dysfunction

Mitochondria generate ATP, sense the environment around them, and participate in signaling to initiate key processes in the body. As sensors, mitochondria can detect the presence of things like toxins, infectious agents, and even biophotons emitted by gut bacteria and food. In their signaling role, mitochondria initate apoptosis, the death of abnormal cells such as cancer cells. Mitochondrial signaling is also involved in the Cell Danger Response, which is part of the body's response to threats like infections.

Mitochondria possess their own DNA, which can become damaged. Mitochondria are damaged by toxins like heavy metals, oxidative stress, excess polyunsaturated fatty acids, loss of proteostasis, and more. Damage to mitochondria causes mitochondrial dysfunction, which is at the heart of degenerative disease processes.

Cellular Senescence

Cells that have lost enough function that they stop dividing are termed "senescent cells". In some cases, senescent cells produce inflammatory compounds that damage surrounding tissue. Senescent cells can also secrete compounds that convert other cells into senescent cells, so they are sometimes referred to as "zombie cells".

Cellular senescence can be triggered by telomere shortening, DNA damage, mitochondrial damage, cancer, viral or bacterial infections, oxidative damage, nutrient imbalance, and mechanical stress. Multiple diseases involve cellular senescence, including metabolic syndrome, diabetes (types I and II), heart disease, Alzheimer’s disease, and Parkinson’s disease. The chronic inflammation driven by cellular senescence is also a key mediator of many symptoms and subclinical pre-disease states that tend to become increasingly common as people get older.

Stem Cell Exhaustion

Stem cells are "undifferentiated" cells that can become "differentiated" cells with specific functions in the body in order to replace damaged cells and repair damaged tissues. But stem cells can become depleted, and they age just like other cells. As they age, they can lose their differentiation capacity, depriving us of the rejuvenative healing powers of youth.

Altered Intercellular Communication

The body maintains homeostasis via intercellular communication, which is communiation between cells of the body. Neurotransmitters, hormones, cytokines, chemokines, and biophotons are among the mechanisms of intercellular communication. Chronic inflammation is one of the factors that interferes with intercellular communication, resulting in reduced responsiveness of the immune system, insulin receptors, reproductive organs, endocrine glands, blood pressure regulatory system, and more .

Chronic Inflammation

Most of the hallmarks of aging described so far can involve chronic Inflammation, which is why it is sometimes referred to as "inflammaging". There are very few disease processes that do not involve some degree of chronic inflammation, including some that you might not normally associate with inflammation, such as osteoarthritis and osteoporosis. Key inflammatory mediators include interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL1-beta), nuclear factor kappa-light-chain enhancer of activated B (beta) cells (NFkB), and the NLRP3 inflammasome.

Dysbiosis

Dysbiosis is an imbalance in the microbiome of the body, especially in the gastrointestinal tract but also in other parts of the body such as the nasal and sinus cavities, mouth, throat, lungs, skin, bladder, breasts, vagina, etc. Dysbiosis is one of the main drivers of chronic inflammation. Dysbiosis can also be an indirect result of chronic inflammation and altered cellular communication to the extent that they reduce immune response, which is important to maintaining a healthy microbiome. Species diversity is a key factor in the health of the microbiome, and dysbiosis is characterized in part by loss of diversity. While most people lose microbiome diversity and develop dysbiosis as they get older, centenarians possess microbiomes that are similar to those of young people.

How The Hallmarks of Aging Pertain to Common Health Challenges

The hallmarks of aging are essentially the same factors underlying the symptoms and conditions that people come to me for help with. So reversing the hallmarks of aging is implicitly (and sometimes explicitly) embedded in the system I use for helping people with their health challenges. To learn more about this system, download the Bio-Individual Blueprint Roadmap and watch the walkthrough video. And if you think we might be a fit to work together, book a time for to chat about it after watching the video.

In the next post, we will explore what I call "youth factors" related to the hallmarks of aging that we can optimize to slow and reverse aging.