A decline of the epigenome could be one of the most important reasons causing the aging process. The epigenome determines which genes are active and provides instruction for genes that need to be kept inactive. During the process of aging, the epigenome tends to dysregulate i.e., genes that should be deactivated are activated (like cancer-promoting genes), and genes that should be activated are deactivated (like genes that protect and repair our cells). This, in turn, leads to instability in the DNA.

Proteins are the building blocks and workhorses of our cells. A cell contains millions of proteins. These proteins are continuously built up and broken down in a complex and intricate recycling process. However, this process is not deterministic. Often proteins are not broken down and start to accumulate in and around the cells. This leads to the process of coagulation of the proteins, which hampers the functioning of the cells. This “protein toxicity,” caused by what is also known as a “Loss of Proteostasis,” is one of the reasons for causing the aging phenomenon.

The mitochondria are the powerhouses of the cells. Each cell can contain hundreds to thousands of mitochondria. It produces the energy that the human body needs to live. As humans succumb to aging, mitochondrial dysfunctions often occur. Without sufficiently functioning mitochondria, the cells decline, leading to symptoms of aging.

The telomeres are the outer ends of the DNA strand. It is composed of repetitive DNA and protects the ends of the DNA. With each cell division, the telomeres shorten, until it can no longer protect the DNA. In non-dividing cells (in which the telomeres do not shorten), it does not cause an issue. Still, these cells can become damaged because the dividing surrounding cells that nourish and protect these cells become damaged due to telomere shortening. Also, during aging, the telomeres become damaged, not just shortened, which further stresses the cells.

During aging, an increasing number of senescent cells appear in the tissues. Senescent cells are also called “zombie cells”: these cells should normally have died but tend to linger in the body perpetually. Normally, these cells should be self-eradicated because of this damage, but due to certain reasons this process does not take place. These cells secrete substances that damage the healthy surrounding cells. Accumulation of senescent cells in the skin contributes to wrinkles. Senescent cells in the blood vessels make the blood vessels stiffer and more prone to atherosclerosis. It also contributes to brain inflammation and aging.

Some scientists speculate that DNA damage can accelerate aging indirectly. To repair a DNA break, specific repair enzymes are displaced from regions where these enzymes normally help to stabilize the epigenome. During extreme DNA breakage, the enzymes cannot maintain the epigenome appropriately and are transported to repair the DNA breaks, which could result in a dysregulated epigenome, an important driver of aging.

Stem cells grow new cells that replenish the tissues. During aging, the amount of stem cells in the body declines. Additionally, the remaining stem cells function less optimally. This leads to our tissues being less maintained, repaired, and replenished, contributing to aging. The decline in stem cells is caused because of the aforementioned aging mechanisms, such as epigenetic dysregulation, mitochondrial dysfunction, protein accumulation, and crosslinking, which also happen in stem cells.

As the human body ages, instability arises in communication between cells. Senescent cells, secrete substances that damage other healthy cells. These senescent cells also secrete pro-inflammatory substances that travel throughout the body and cause damage everywhere. During aging, desensitization of cells to specific triggers, like insulin or other nutrients, leading to insulin resistance, a precursor of diabetes, or resulting in aging switches (like mTOR) that are activated for periods longer than necessary.

Cross-linking refers to the molecular issues that arise when glucose binds to protein. This process occurs under the presence of oxygen, and as we age there are increased odds that oxygen comes in contact with glucose and protein to activate the cross-linking transition. Cross-linking of proteins may also play a role in the hardening of collagen and cardiac enlargement, increasing the risk for cardiac arrest. In addition to these potentially serious implications, many believe that cross-linking is responsible for age-related skin changes including wrinkles and reduced elasticity.

Our metabolic activities can put stress on our cells. When there is an increased amount of activity and changes in nutrient availability and composition in our body, the cells age faster. As cells age due to various stresses it is subjected to, these damaging events also deregulate various nutrient sensing molecules. For example, a misguided hypothalamus may signal for greater food intake when the body does not really require it. This can result in age-related obesity, diabetes and other metabolic syndromes.