Live Well, Live Long
Science-backed tips for a healthier & longer life
Volume 6: Hallmarks of Ageing
Welcome back to Live Well, Live Long. In this volume, we’re diving into the fascinating concept of the Hallmarks of Aging—the foundational mechanisms that govern the ageing process at the cellular level. Understanding these hallmarks is crucial for unlocking the secrets to healthier, longer lives.
Why Are the Hallmarks of Aging Important?
It’s crucial to recognise why discussing and understanding ageing is so important. Ageing significantly impacts our quality of life, and by studying it, we can explore ways to manage and mitigate its effects. In this article, we will delve into the various Hallmarks of Aging.
Ageing is a complex phenomenon, involving interconnected processes within our bodies that impact our quality of life. By identifying the hallmarks of ageing, scientists have created a framework to understand and potentially reverse the age-related decline.
A biological process must meet three essential criteria to qualify as a hallmark of ageing:
-First, it must manifest during normal ageing, becoming more apparent as the organism ages.
-Second, its experimental aggravation should accelerate ageing, confirming its direct influence on lifespan and age-related decline.
-Third, improving or reducing the impact of the hallmark should extend both lifespan and health span, offering the potential for therapeutic interventions that promote healthier ageing.
Understanding these hallmarks can pave the way for breakthroughs in slowing or reversing the ageing process.
Let’s explore the key hallmarks of ageing and their implications.
The Key Hallmarks of Aging
-Genomic Instability
-Genomic instability refers to the natural tendency of the genome to lose information due to various internal and external agents. This loss poses a significant challenge to the body’s proper functioning.
The genome provides the instructions for producing proteins essential for health. When genomic instability causes loss of these instructions, protein synthesis can be impaired or halted, leading to health issues and ageing.
Proteins are crucial for cellular functions, including damage repair and metabolic regulation. Disruption in protein synthesis due to genomic instability can profoundly affect health and longevity. As genomic instability progresses, the cumulative loss of genetic information accelerates ageing, emphasizing the importance of maintaining genomic integrity to prevent age-related decline.
Why it matters:
The cumulative loss of genetic information accelerates ageing and increases the risk of diseases. Maintaining genomic stability is crucial for longevity.
-Telomere Attrition
Telomere, as we know, are protein-DNA structures at the ends of chromosomes that protect the ends of DNA and help control a cell’s lifespan. Telomere Attrition is another hallmark of ageing, involving the gradual shortening of telomeres. Telomeres play a vital role in preventing DNA damage during replication. With each cell division, telomeres naturally shorten. Eventually, when they become too short, cells can stop dividing or become senescent, which leads to disrupted tissue function & contributes to many age-related diseases.
Why it matters:
Telomere shortening is a cellular clock that limits the lifespan of cells. Protecting telomeres through lifestyle changes or medical interventions can potentially delay the onset of age-related conditions, such as cardiovascular diseases, and promote healthier aging.
| Did you know? As per India Ageing Report 2023, the current elderly population of India is 153 million (aged 60 and above) and is expected to reach a staggering 347 million by 2050. |
-Epigenetic Alterations
Epigenetic alterations refer to changes in the epigenome, which essentially is like a set of on & off switches for genes, which will allow cells to have different properties even though they have the same DNA. When the epigenome is altered, these critical switches malfunction, leading to a loss of cellular identity. This deregulation can cause cells to behave abnormally, contributing to various health issues and diseases.
Why it matters:
Epigenetic alterations contribute to a wide range of age-related conditions, from cancer to metabolic disorders.
Loss of Proteostasis
It refers to the failure of the protein-building machinery of the cell and the accumulation of misfolded proteins. This failure in maintaining proper protein folding, assembly & degradation within the cell, leads to cellular and organ level dysfunction.
Why it matters:
Maintaining proteostasis is vital for preventing neurodegenerative diseases like Alzheimer’s.
Deregulated Nutrient Sensing
Deregulated nutrient sensing is a hallmark of aging, and describes how our cells fail to sense and respond appropriately to the levels of available nutrients. Changes in nutrient sensing pathways affect how cells distribute their energy between energy-saving and energy-demanding processes like cell division. Getting this balance wrong may accelerate age-related changes within the cell.
Deregulated nutrient sensing systems, which monitor nutrient availability in the body, can become impaired with age, affecting cellular function and overall health.
Our cells sense and respond to nutrient levels to balance energy use between maintenance and growth. Ageing disrupts these pathways, leading to metabolic dysfunction.
Why it matters:
Deregulated nutrient sensing accelerates age-related cellular changes, impacting overall health.
-Mitochondrial Dysfunction
Mitochondrial dysfunction refers to a decline in the ability of mitochondria to function properly, particularly in their capacity to produce energy. This decline occurs as mitochondria accumulate damage in their genetic material, which is partly separate from the rest of the human genome and thus less protected. As this damage accumulates, the efficiency and effectiveness of the mitochondria diminish, leading to various health issues.
Why it matters:
Healthy mitochondria are essential for energy-intensive organs like the heart and brain.
-Cellular Senescence
Cellular senescence is a state in which cells stop dividing. This occurs after a cell has undergone a certain number of divisions (typically 40-60 in humans) or when a cell sustains irreparable damage. While senescence plays a crucial role in protecting against cancer by preventing damaged cells from proliferating, it can become problematic as we age. The accumulation of senescent cells contributes to ageing and age-related diseases.
Why it matters:
Clearing senescent cells could slow ageing and improve tissue function.
-Stem Cell Exhaustion
When too many of our stem cells are not working anymore, they cannot produce more cells to replace the ones that die, because they are somewhat dead themselves. This means the cell count in some of our tissues decreases with age, making us vulnerable to many diseases.
Why it matters:
Stem cell exhaustion plays a significant role in immune decline with age.
-Altered Cellular Communication
Altered cellular communication refers to changes in the signals that cells throughout the body send to each other. Intercellular communication is like a biological telecoms network, allowing even distant cells to coordinate their activities. With age, an increasing number of harmful signals are released by certain cells (such as senescent cells), which can drive the ageing process in multiple organ systems.
Why it matters:
Restoring healthy communication between cells could prevent systemic ageing effects.
-Disabled Macroautophagy
This occurs when a body’s cells are unable to perform a cellular self-cleaning known as autophagy. This leads to the accumulation of damaged or dysfunctional cellular components and is associated with cancer, and metabolic and neurological disorders.
Why it matters:
Impaired autophagy prevents cells from eliminating harmful debris, which can disrupt cellular function and increase the risk of chronic diseases. Supporting autophagy through diet and exercise can promote cellular health and longevity.
-Dysbiosis
Dysbiosis is a disruption in the normal microbial community, reduction of beneficial kind & overgrowth of the harmful kind leads to brain dysfunction, poor immune health & chronic inflammation.
Why it matters:
Dysbiosis is linked to inflammation, brain dysfunction, and a weakened immune system.
-Chronic Inflammation
Inflammation is a chronic, low-grade inflammatory state that occurs as part of ageing and can be influenced by lifestyle factors. It can contribute to age-related diseases, including cardiovascular disease, diabetes, and neurodegenerative disorders.
Why it matters:
Unchecked chronic inflammation accelerates tissue damage and ageing, increasing susceptibility to age-related conditions. Addressing inflammation through lifestyle changes and medical interventions can significantly improve healthspan and reduce the burden of disease.
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Why Are Hallmarks Important?
By understanding these mechanisms, researchers aim to develop therapies that slow or reverse ageing. Ageing, once thought to be inevitable, may be influenced by lifestyle choices and medical advancements.
What’s Next?
In the upcoming articles, we’ll discuss how lifestyle interventions—such as diet, exercise, and stress management—can help mitigate these hallmarks, offering hope for a healthier future.
Stay tuned for more insights into the science of ageing and longevity!
References
1) India Ageing Report 2023 – United Nations Population Fund
2) Hallmarks of Aging: An Expanding Universe – Carlos et al., 2023