There are ongoing debates about the role of cellular senescence in aging, but a group of researchers may have information that can shed some more light on this.

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In this article:

  1. What Is a Systems Biology Perspective?
  2. What Is Cellular Senescence?
  3. What Are Age-Related Diseases?
  4. What Are the Genetic Similarities Between CS, ARD, and LAGs?
  5. What Causes The Genetic Links Between CS, ARD, and LAGs?
  6. What Are the Common Signaling Pathways Between CS, ARD, and LAGs?

Understanding the Role of Cellular Senescence in Aging and Age-Related Diseases from a Systems Biology Perspective

In the 2011 issue of Aging, Researchers Tacutu, Budovsky, Yanai, and Frafeld published an article to clarify the role of cellular senescence in age-related diseases and, ultimately, longevity.

What Is a Systems Biology Perspective?

The systems biology perspective offers a holistic approach to understanding organisms and their function. In their article, the researchers use this perspective to understand the complex nature of aging by focusing on the interaction of different components such as genes, molecules, and signaling pathways.

What Is Cellular Senescence?

Cellular senescence (CS) refers to a state where cells are metabolically active but are unable to continue dividing and re-enter the cell cycle. The researchers describe it as a state of “irreversible growth arrest.”

Apart from that, other cellular senescence markers include:

  • Cell hypertrophy – This causes cells and tissues to increase in size.
  • An increase in metabolic activity – This includes an increase in the production of organelles and macromolecules (RNA, protein, lipid).
  • An increase in the secretion of pro-inflammatory substances – It can change the structure and function of the surrounding cells and tissues.
  • Resistance to apoptosis – It refers to cellular death, which allows the body to eliminate and replace cells.

Features of CS has been found in various cell types such as:

  • Human fibroblasts – connective tissue cells that produce collagen
  • Keratinocytes – epidermal cells that produce keratin
  • Endothelial cells – cell lining of various organs including blood vessels
  • Lymphocytes – refers to white blood cells
  • Adrenocortical cells – the cells surrounding the adrenal gland
  • Vascular smooth muscle cells – cells in the muscles of blood vessel walls
  • Chondrocytes – cells in cartilage
  • Neurons – nerve cells that transmit signals
  • Myocardiocytes – refers to cardiac muscle cells
  • Adipocytes – cells that store fat in connective tissues

The researchers assert that senescent cells contribute and interact with age-related conditions. There are genetic and functional similarities between CS, age-related diseases (ARD), and longevity-associated genes (LAGs).

What Are Age-Related Diseases?

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Age-related diseases are diseases that increase in incidence as the population ages. Examples of age-related diseases include:

  • Cardiovascular diseases
  • Cancer
  • Arthritis
  • Cataracts
  • Osteoporosis
  • Type 2 diabetes
  • Hypertension
  • Alzheimer’s disease

Researchers believe that the accumulation of senescent cells contributes to the development of age-related diseases.

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What Are the Genetic Similarities Between CS, ARD, and LAGs?

An extensive analysis reveals that 19% of CS genes are similar to LAGs. On top of that, 53% of CS genes involve at least one ARD.

The following ARDs share genetic overlaps with CS:

  • Cancer (53%)
  • Atherosclerosis (20%)
  • Alzheimer’s disease (9%)
  • Type 2 diabetes (9%)

CS also shares genetic overlaps with processes that may contribute to ARD, such as oxidative stress (21%) and chronic inflammation (8%).

There’s also an overlap between CS genes and genes essential for growth and development (38-55%). Keep in mind, genes essential for growth and development are necessary early on, but these same genes may lead to harmful health outcomes in the later stages of life.

There are also notable protein-protein interactions (PPIs) between CS, ARD, and LAG proteins. The PPI allows them to form protein complexes.

On top of that, they also share many external protein partners. Overall, over 80% of CS genes overlap with either ARD genes or LAG genes.

What Causes the Genetic Links Between CS, ARD, and LAGs?

The researchers believe these genetic links are partly because of common regulatory molecules (miRNA). The analysis shows that 39 miRNA targets 40 CS genes.

The same 39 miRNA also targets cancer, atherosclerosis, and other ARD genes. They also found that miRNA and cancer genes may bridge CS to other ARDs.

The presence of cancer genes predict links between CS and other ARDs. When they removed cancer genes in the ARD set, there was no increase in CS.

Interestingly, if you remove ARDs from cancer sets, there’s no significant change in CS. So it’s possible that cancer genes play a vital role in linking CS with other ARDs.

What Are the Common Signaling Pathways Between CS, ARD, and LAGs?

The researchers also found several common signaling pathways between CS, ARDs, and other aging processes. Surprisingly, many of these are growth-promoting pathways.

It may seem confusing because CS is a state of irreversible growth arrest. But the researchers found that when quiescence cells are stimulated with growth-promoting mediators, it can induce CS.

The common growth-promoting pathways are also linked to cancer-associated pathways. This association makes sense because cell proliferation and growth are characteristics of cancer cells.

CS signaling pathways are linked to bladder cancer, colorectal cancer, chronic myeloid leukemia, glioma, and melanoma pathways. All of these pathways involve tumor-suppressing signaling.

Apart from that, all of these pathways play a role in the cell’s stress response, which links CS to aging and ARDs even further.

There is an interconnection between CS, aging, longevity, and ARDs. They share common genes, molecules, and pathways.

Identifying these commonalities is an important step in understanding the complex process of aging. With these findings, the researchers believe it’s possible to develop pro-longevity and anti-ARD strategies by regulating CS.

If you’re interested in learning more about cellular senescence and how it could impact your overall health, talk to an integrative health specialist today.

What do you think of these new findings? Share your thoughts with us in the comment section below.

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Source:
Molecular links between cellular senescence, longevity and age-related diseases – a systems biology perspective – NCBI.gov