The 12 Hallmarks of ageing

1. Dysbiosis

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Dysbiosis refers to the imbalance of the gut microbiome, the community of microorganisms in the digestive system. As we age, the composition of the gut microbiota can become altered, leading to impaired digestion, reduced immune function, and increased inflammation. These changes in the gut microbiome are linked to age-related diseases such as obesity, diabetes, and neurodegenerative conditions.

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Key Implications: Maintaining a healthy microbiome through diet, probiotics, and prebiotics can promote longevity and improve overall health.

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2. Genomic Instability

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Over time, our DNA accumulates damage from various sources such as radiation, toxins, and replication errors. Genomic instability refers to the increased rate of mutations, which can disrupt normal cell function and lead to conditions like cancer. As we age, the body's ability to repair DNA diminishes, contributing to ageing and disease.

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Key Implications: Targeting DNA repair mechanisms and reducing environmental DNA damage may help mitigate genomic instability.

 

3. Telomere Attrition

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Telomeres are protective caps at the ends of chromosomes that shorten with each cell division. Telomere attrition, or shortening, is a key marker of cellular ageing. When telomeres become too short, cells enter a state of senescence or die, leading to tissue dysfunction and contributing to age-related diseases.

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Key Implications: Strategies to preserve telomere length, such as healthy lifestyles and stress reduction, may delay cellular ageing.

 

4. Epigenetic Alterations

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Epigenetics refers to changes in gene expression that do not involve alterations to the DNA sequence. As we age, these epigenetic changes can become dysregulated, leading to abnormal gene expression patterns. This can affect many cellular functions, from DNA repair to inflammation, and promote the onset of age-related diseases.

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Key Implications: Understanding and potentially reversing harmful epigenetic changes could offer new therapeutic strategies for ageing.

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5. Loss of Proteostasis

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Proteostasis refers to the balance and stability of proteins within cells. As we age, the systems responsible for maintaining protein quality, such as chaperones and proteolytic pathways, become less efficient. Misfolded or damaged proteins accumulate, contributing to conditions like Alzheimer’s and Parkinson’s diseases.

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Key Implications: Enhancing protein-folding mechanisms and reducing protein aggregates may improve cellular function and slow ageing.

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6. Disabled Macroautophagy

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Macroautophagy, commonly referred to as autophagy, is the process by which cells recycle damaged or unnecessary components. With age, this self-cleaning process becomes less efficient, leading to the accumulation of cellular debris and dysfunctional organelles. Impaired autophagy is associated with a variety of age-related diseases, including neurodegeneration and cancer.

 

Key Implications: Promoting autophagy through lifestyle interventions (e.g., fasting) or pharmacological agents could help maintain cellular health and longevity.

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7. Deregulated Nutrient-Sensing

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The body's ability to sense and respond to nutrient levels changes with age, leading to metabolic imbalances. Key nutrient-sensing pathways, such as insulin and mTOR signaling, become dysregulated, contributing to metabolic disorders like diabetes and obesity.

 

Key Implications: Modulating nutrient-sensing pathways, such as through caloric restriction or specific dietary interventions, can enhance metabolic health and extend lifespan.

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8. Mitochondrial Dysfunction

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Mitochondria are the energy-producing organelles of the cell, and their efficiency declines with age. Mitochondrial dysfunction leads to reduced energy production, increased oxidative stress, and impaired cell function. This decline plays a central role in age-related conditions, including muscle weakness, neurodegenerative diseases, and metabolic disorders.

 

Key Implications: Enhancing mitochondrial function through lifestyle changes, exercise, and potential therapeutics could support energy production and reduce the impact of ageing.

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9. Cellular Senescence

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Cellular senescence is the process by which cells lose their ability to divide and function. These cells accumulate with age, contributing to tissue dysfunction, chronic inflammation, and age-related diseases. Senescent cells secrete harmful signals that can damage neighboring healthy cells.

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Key Implications: Therapies that target and eliminate senescent cells, known as senolytics, are being developed to combat age-related diseases.

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10. Stem Cell Exhaustion

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Stem cells are responsible for regenerating damaged tissues and maintaining the body's ability to repair itself. With age, stem cell function declines, leading to reduced tissue regeneration and the onset of age-related conditions, such as sarcopenia and osteoporosis.

 

Key Implications: Strategies to rejuvenate or replace exhausted stem cells could help restore tissue function and improve longevity.

 

11. Altered Intercellular Communication

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As cells age, the way they communicate with each other changes, often becoming less efficient or even harmful. This altered communication contributes to inflammation, impaired immune function, and tissue damage. Chronic inflammation, known as “inflammaging,” is a hallmark of ageing that exacerbates many age-related diseases.

 

Key Implications: Anti-inflammatory interventions and improving cell signaling pathways may help reduce age-related damage and inflammation.

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12. Chronic Inflammation

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Chronic, low-grade inflammation, often referred to as "inflammaging," is a significant contributor to the ageing process. Inflammation becomes dysregulated with age, leading to increased risk of cardiovascular disease, neurodegeneration, and autoimmune disorders.

 

Key Implications: Controlling chronic inflammation through lifestyle, diet, and medical treatments could significantly reduce the impact of age-related diseases.