Why Do We Age? | Altered Intercellular Communication

During aging, the environment our cells live in changes: it becomes pro-inflammatory, pro-aging, and damaging. This makes our cells age faster, leading to a vicious cycle, given damaged, aged cells secrete harmful substances that damage healthy cells.

How the Changing Environment Our Cells Bathe In Make Them Age Faster

When we get older, many substances start to circulate in our body that accelerate aging. These are specific proteins, hormones, peptides and metabolic substances. 

Also, during aging, we see a decline in circulation of substances that protect our cells or that keep our cells in a good condition. 

The first insights regarding the importance of this extracellular milieu came from “heterochronic parabiosis” experiments, in which an old and a young mice were sown together, joining their blood circulatory systems, so that young blood flowed through the arteries of the old mouse and vice versa. 

Exposed to the blood of young mice, the old mice seemed to be somewhat rejuvenated, in the sense that their organs and tissues could regenerate better again. Unfortunately, the young mice exposed to the blood of old mice seemed to age faster. 

Scientists are now trying to identify the substances in young blood that can rejuvenate cells. And they are also looking to identify the substances that accelerate aging. Many of these substances promote inflammation. 

The Aging Process

We see a considerable increase in inflammation everywhere in the body during aging. This aging-related increase of inflammation is called “inflammaging”. 

“Inflammaging” is an important component of the altered intercellular milieu we see during aging. 

Where does this inflammaging come from? There are many causes: 

• Senescent cells start to arise everywhere in our body. They secrete proinflammatory substances that damage healthy cells. 
• When we get older, we tend to accumulate more adipose tissue, especially around the organs in our abdomen (this is called a “beer belly”). Often, in this fat tissue fat cells die off, scattering their contents around, which induces macrophages that want to clear everything up. These macrophages secrete inflammatory substances that travel everywhere around the body, and even reach your brain. 
• During aging, our gut becomes more leaky. In scientific terms this is called “increased intestinal permeability”. Also, during aging, our microbiome changes: it becomes less diverse, and there is more risk of overgrowth of specific unhealthy bacteria. An altered aged microbiome, in combination with increased gut permeability enables toxic substances to leak from the gut into the bloodstream, fanning inflammation everywhere in the body. 
• An aged immune system works less properly: it becomes too overactivated, even when there are no direct inflammatory stimuli. The aging and dysregulation of the immune system is called “immunosenescence”. 
• A declining immune system allows pathogens to roam around freely in the body, causing inflammation.  
• Aged, mare fragile and thinner skin lets harmful substances permeate the skin more, and induce inflammation. 
• In-born viruses (retrotransposons) jumping around in our DNA also induce inflammation. These retrotransposons activate inflammatory pathways, just like normal viruses do.  
• When we get older, we are less able to process nutrients, such as sugars and fats. These nutrients tend to linger longer around in the bloodstream, causing inflammation. Sugar induces inflammation, as do fats, especially long-chain saturated fats, which can directly activate white blood cells making them to release proinflammatory substances. 
• During aging, our mitochondria become more and more damaged. Damaged mitochondria secrete substances that fan inflammation. Such substances are called DAMPs (damage-associated molecular patterns) and include pieces of freely circulating mitochondrial DNA. These substances induce a strong immune reaction, especially given mitochondria have a bacterial origin, and the immune system is of course very vigilant to combat everything bacteria-related. 
• When we get older, higher levels of blood clotting (coagulation) factors are circulating in the bloodstream. Coagulation factors are proteins that induce blood clotting. But they also induce inflammation. Most coagulation factors are made in the liver, but senescent cells can also secrete coagulation factors. 

These are some examples of processes that induce aging-related inflammation, or inflammaging. This systemic, body-wide, pro-inflammatory environment damages healthy cells and stem cells, leading to a frail, aged body. 

Besides pro-inflammatory substances, many other substances that accelerate aging course through our bloodstream and cellular fluids. 

Experiments like heterochronic parabiosis, in which old and young mice share the same blood circulatory system,  demonstrate that in young mice substances circulate that have rejuvenation effects, and that the blood of old mice contains substances that accelerate aging. 

During aging, the levels of various harmful substances increase in our bloodstream, such as renin, angiotensin, insulin, IGF, cytokines, interferons, TNF,  hormones. These substances damage healthy cells and inhibit the functioning of stem cells, which are needed to maintain and replenish the tissues. 

This altered intercellular communication creates a pro-aging environment in the body, leading to a decline in cellular function and a decline of our body as a whole. 

NOVOS’ Approach to Altered Intercellular Communication.