Aging is a complex process that starts deep down in our cells. In the past few decades, researchers have identified the fundamentals of why we age at the cellular level. Let’s take a look!
To study cellular aging, we need a metric to measure it. That’s where biological age comes in.
Everyone ages at a different pace, and therefore it’s important to distinguish your chronological age from your biological age.
Your chronological age is the number you celebrate every birthday, which you have little control over. Your biological age, on the other hand, is more persuadable. It reflects your overall health. (Read more about how we derive biological age here!
A 2013 study first established the nine hallmarks of aging and divided them into three groups: primary, responsive, and integrative hallmarks. The primary hallmarks are the foundational sources of cell damage whereas the responsive and integrative hallmarks are relatively reactive. The primary hallmarks are the root causes of aging1.
The four primary hallmarks are telomere erosion, genomic instability, epigenetic alterations, and loss of proteostasis. In this article, we’ll be focusing on the first three concepts1.
Telomeres are the protective caps at the end of your DNA, like the protective plastic at the end of your shoelaces! These caps prevent DNA damage brought on by cell replication. Here’s cell replication in a nutshell:
This process is not seamless. As chromatid pairs are pulled apart, the DNA at their ends takes damage. Consistently sustaining this level of DNA damage would typically be disastrous for the cell. That’s why we have telomeres to bear the brunt of the wear and tear in cell replication.
When chromatid pairs are pulled a part, their ends take damage. That’s why we have meaningless DNA repeats called telomeres at the end of our chromatids Thus, when chromatid pairs are pulled apart, telomeres take the damage.
Unfortunately, telomeres are not endless. Each cell division deteriorates these telomeres until they’re critically short, and can no longer protect our DNA. After taking some replication-induced DNA damage, the cell activates a DNA damage response. This informs the cell that it’s at the end of its life, sending it into a zombie-like state to eventually undergo apoptosis, cell suicide2.
Sometimes that last part doesn’t go as planned. After the cell enters a zombie-like state, known as senescence, it occasionally doesn’t die. This leaves it as a senescent cell. Cellular senescence has its own host of issues, such as promoting inflammation. In fact, cellular senescence is one of the responsive hallmarks of aging1.
Even if things do go as planned, the result is cell suicide. Shorter telomeres lead to shorter cell lifespans, which is not ideal for longevity. Thus, several studies focus on maintaining telomere length via lifestyle changes and potential therapies.
Our cells sustain DNA damage every day. Internally, this is a result of unwanted oxidation from free radicals. (Read more about using antioxidants to fight radical here!)
When you oxidize DNA, you change its structure, leading to breakages. There are repair pathways that replace damaged DNA molecules, but these pathways get less effective with age. Eventually, these breaks start to accumulate, and the cell activates a DNA damage response. This hallmark also leads to apoptosis (programmed cell death) and cellular senescence, a responsive hallmark of aging3.
The epigenome is virtually another layer on the genome. Using DNA methylation, the epigenome controls the activation and deactivation of genes. While our genome is unchanging from birth, our epigenome is dynamic.
When our DNA sustains damage, the reparation pathways will usually step in to replace the damaged DNA molecules. However, DNA repair will frequently get our epigenetic expression wrong. So although the DNA molecule is repaired, its level of expression is different. This is referred to as an epigenetic alteration4.
A change in gene expression can suppress crucial genes and leave a cell dormant or activate genes that can send a cell into senescence. Most of the age-related changes we experience are consequences of epigenetic alterations.
Our epigenome and DNA methylation patterns are a strong indicator of overall well-being, making it a terrific metric for biological age. In fact, GrimAge, the biological clock we use at FOXO, employs DNA methylation patterns to predict biological age.
Our epigenome is also highly responsive to our lifestyle and environment; this makes it a superb source of personalized health data. With a detailed analysis of your gene expression, FOXOTM returns a Longevity ReportTM with a current reflection of your cellular health as well as strategies to determine what your cells need to stay young!
Studying and analyzing the fundamentals of aging not only tells us where we stand, but it tells us how to do better! Let FOXO do the research, so you can focus on staying healthier, longer.