Scientists define aging as “a progressive loss of physiological function that can increase our overall susceptibility to disease and death.” While this definition isn’t exactly cheerful for most of us, longevity scientists see it as a thrilling puzzle just waiting to be solved. Why do we lose physiological function as we get older? Why are certain diseases, like Alzheimer’s, arthritis, and osteoporosis so inextricably linked to aging? And most importantly: what can science do to slow the loss of physiological function to help people lead longer, happier, healthier lives?

We may be decades away from having the answers to all of these questions. But recent scientific breakthroughs have identified the factors behind the first very important question: why do we age?

Longevity scientists have spent decades examining a range of species in search of commonalities that may hold the clue to why we age. The result: twelve common factors observed across species known as the hallmarks of aging. Although each hallmark is unique, they all interact with one another to contribute to the signs of aging. By understanding these hallmarks and how they interact, not only can we better understand aging, we can begin to understand how to reverse its impacts.

Science is always learning! Researchers originally identified just nine hallmarks of aging. But more recently, three new hallmarks of aging have been classified and published in the latest version of Cell’s landmark paper, “Hallmarks of Aging”.

The original 9 hallmarks:

1. Genomic Instability: As we age, numerous factors can damage our DNA. The more damage our DNA accumulates over time, the higher our chances are of developing age-related disease and signs of accelerated aging.
   
   
2. Telomere Attrition: Telomeres, the compound structures at the end of each of our chromosomes, shorten as we age. The shorter our telomeres get, the harder it is for our cells to multiply–making it more difficult for our tissues to regenerate and repair themselves. This compromised cell proliferation can lead to a number of age-related diseases.
   
   
3. Epigenetic Alterations: Throughout the course of our lives, our DNA can be chemically modified by both internal and external factors – for example, by the foods we eat or by UV exposure. These superficial DNA modifications determine which of our genes will be expressed or not expressed. As our DNA accumulates alterations with age, we’re more likely to see the activation of genes linked to inflammation and aging.
   
   
4. Loss of Proteostasis: Proteostasis maintains proper folding, degradation, trafficking, and biogenesis of proteins in our cells. As we age, proteostasis diminishes, which means our bodies start to create misfolded proteins. As these proteins accumulate in the body with time, they can lead to many issues, including chronic inflammation.
   
   
5. Deregulated Nutrient-Sensing: Metabolic activity, while essential to life, puts stress on our cells. To prevent this, our cells have nutrient sensing pathways that make sure they’re taking in the right amount of nutrition–enough to sustain life, but not too much to stress the system. As we age, these nutrient-sensing pathways deregulate. This is thought to be a primary factor behind age-related metabolic diseases like diabetes and obesity.
   
   
6. Mitochondrial Dysfunction: Known as the “powerhouse of the cell,” mitochondria keep our cells healthy and functioning. As we age, our chance of mitochondrial dysfunction increases, thereby speeding the rate of apoptosis – cell death.
   
   
7. Cellular Senescence: Senescent cells are cells at the end of their life cycle that can no longer divide. When we’re young and healthy, our bodies naturally clear these cells away. But as we age, our bodies become less efficient at removing senescent cells. This leads to an accumulation of senescent cells that has been shown to increase inflammation and contribute to a number of chronic diseases.
   
   
8. Stem Cell Exhaustion: Stem cells are the vital source from which all of our cells emerge. As we age, the activity of our stem cells slowly decreases. This occurs for a number of reasons; for example, pro-inflammatory signals secreted by senescent cells reduce stem cell activity. This, in turn, makes it harder for our tissues to regenerate in the same way that they do when we are young.
   
   
9. Altered Intercellular Communication: Cells are constantly communicating with one another to properly function. As we age, the signaling pathways our cells use to communicate can become disrupted. Without proper communication between cells, various forms of damage can occur.

The additional three hallmarks:

10. Chronic Inflammation: As we age, inflammation increases throughout our bodies in a process called inflammaging. This inflammation is a result of multiple derangements caused by other hallmarks and can be observed by measuring concentrations of inflammatory cytokines and biomarkers like CRP.¹² Over time, this inflammation can have systemic manifestations, including arteriosclerosis, neuroinflammation, and osteoarthritis.
    
    
11. Disabled Macroautophagy: Autophagy is the process by which our cells clean themselves. When this process is disrupted, cells can experience a build-up of waste, reduced elimination of pathogens, and enhanced inflammation. There is strong evidence that decreased autophagy is relevant to aging and age-related diseases like metabolic disorders and cancer.
    
    
12. Dysbiosis: Disruption in our gut bacteria can result in dysbiosis and contributes to a variety of conditions, such as obesity, type 2 diabetes, ulcerative colitis, neurological disorders, and cancer. While bacterial diversity is established during childhood and remains relatively stable in adulthood, it undergoes gradual changes during aging, leading to an overall decrease in ecological diversity.

References

• https://pubmed.ncbi.nlm.nih.gov/36599349/