Hallmarks of Accelerated Skin Aging Caused by Epigenetic Hydroxylation Incompetence

What Is Accelerated Skin Aging?

Skin aging is not always a smooth and gradual process. There are certain biological acceleration points where changes occur more rapidly, and the ages of 44 and 60 are two notable examples. This phenomenon is known as accelerated skin aging, or premature aging, which refers to the early appearance of signs such as wrinkles, age spots, and sagging skin. In essence, it is when your skin looks older than your actual age.

Accelerated aging results from a combination of internal (intrinsic) and external (extrinsic) factors.

Why Does Our Skin Age?

Our skin ages because of both built-in biological programming and cumulative external damage over time; in other words, intrinsic and extrinsic aging. Both forms share the same root cause and mechanism: skin epigenetic hydroxylation incompetence (SEHI).

Hydroxylation in DNA and chromatin maintains proper gene expression. Reduced epigenetic hydroxylation causes gene misregulation, including that of repair and antioxidant defense genes. Similarly, hydroxylation in collagen synthesis is essential for forming stable triple-helix collagen. When this process is deficient or dysregulated, collagen becomes weak and dermal aging accelerates.

Fourteen Hallmarks of Accelerated Skin Aging

1. Genomic Instability

This refers to an increased tendency for DNA mutations and other genetic changes to occur during cell division. In essence, the cell’s DNA becomes more prone to errors and alterations as it replicates, increasing the risk of mutations and inherited genetic damage.

2. Telomere Attrition

Telomere attrition refers to the shortening of telomeres, which are protective caps at the ends of chromosomes, during each cell division. This natural process contributes to age-related decline. Critically short telomeres can trigger cellular senescence or cell death.

3. DNA and Histone Methylation

DNA methylation involves adding a methyl group to cytosine bases in DNA, while histone methylation adds methyl groups to histone proteins that help package DNA. Both are epigenetic modifications that regulate gene expression and can either activate or repress transcription, depending on the site and context.

4. Loss of Proteostasis

Loss of proteostasis means disruption of the cellular balance that ensures proteins are correctly folded, functional, and degraded when damaged. This decline in protein quality control is a hallmark of aging. Dysfunction of the proteostasis network, which includes chaperones, proteases, and other regulators, leads to the accumulation of misfolded or aggregated proteins and cellular dysfunction.

5. Deregulated Nutrient Sensing

Deregulated nutrient sensing occurs when the body loses its ability to properly detect and respond to nutrient availability. This disruption impairs metabolic balance, contributing to age-related diseases and decreased longevity.

6. Mitochondrial Damage or Dysfunction

Mitochondrial dysfunction arises when mitochondria fail to produce sufficient energy for cellular processes. Since mitochondria power most cellular activities, their failure affects energy-demanding organs such as muscles, nerves, and skin. Causes include genetic mutations, mitochondrial DNA damage, and environmental stressors.

7. Cellular Senescence

Cellular senescence is a state in which cells permanently stop dividing and enter irreversible growth arrest. Senescent cells become larger and flatter, with altered function and increased secretion of inflammatory molecules. This process is triggered by stressors such as telomere shortening and DNA damage and contributes to tissue dysfunction and age-related disease.

8. Stem Cell Exhaustion

Stem cell exhaustion refers to a reduction in both the number and function of stem cells as we age. This decline impairs tissue regeneration and repair, promoting tissue deterioration and aging. Contributing factors include genomic instability, epigenetic alterations, and chronic cellular stress.

9. Altered Intercellular Communication

This hallmark involves changes in how cells communicate and coordinate with one another. Disruption of these signaling pathways impairs tissue and organ homeostasis and contributes to aging-related decline.

10. Decreased Reactive Oxygen Species (ROS) Defense

This refers to a reduced ability of the body to neutralize reactive oxygen species, which are harmful by-products of cellular metabolism. When antioxidant defenses weaken, oxidative damage accumulates, leading to cellular injury and premature aging.

11. Increased Oxidative Stress

Oxidative stress occurs when there is an imbalance between free radical production and antioxidant defenses. This imbalance causes damage to lipids, proteins, and DNA, accelerating the aging process.

12. Decreased Hydration

Dehydration occurs when the body loses more fluids than it takes in. In the skin, this leads to dryness, reduced elasticity, and a dull appearance, as essential cellular processes require adequate hydration.

13. Chronic Inflammation

Chronic inflammation, often termed “inflammaging,” is a state of persistent, low-grade inflammation associated with aging. It is characterized by elevated inflammatory markers even in the absence of infection or injury. Inflammaging contributes to cardiovascular, neurodegenerative, and metabolic diseases.

14. Dysbiosis

Dysbiosis refers to an imbalance in the skin microbiome. This disruption weakens the skin’s barrier, increases inflammation and oxidative stress, and accelerates cellular aging. Dysbiosis also affects the gut-skin axis, influencing skin health from within.

References

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