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    Why We Age: Understanding the Science Behind Ageing

    Why We Age: Understanding the Science Behind Ageing
    August 5, 2023 Vitality Pro

    Why We Age: Understanding the Science and Genetics Behind Ageing and Health Span

    Virtually every modern human being desires a longer, healthier life that minimises the symptoms and effects of ageing. While ageing is not a disorder or a disease in itself (although some disagree), it is a primary factor in developing a wide range of major diseases, including chronic diseases that negatively impact the quality of life. According to the National Institute on Ageing, many of these diseases also accelerate the natural ageing process, compounding its effects. This results in declines in physical and cognitive function and an overall reduction in healthspan, wellness, and resilience.

    The study of how to live longer, known as longevity science, tries to figure out why we age and what happens in our bodies during this process. Knowing the difference between normal ageing and the biological processes that cause diseases is essential. For example, inflammation is a natural part of healing. But if there’s long-term inflammation in the body without any specific reason, like an infection, it can make people more likely to get diseases related to ageing and make these diseases worse, faster.

    According to Harvard Health, adopting healthy habits enables people to live significantly longer lives. Research from the Harvard T.H. Chan School of Public Health surveyed data from over 78,000 women and 40,000 men, assessing 34 years’ worth of data for the women and 28 years’ worth of data for the men. 

    The researchers assessed information on physical activity levels, diets, body weight, alcohol consumption and smoking. They discovered that people who enjoyed a healthy lifestyle and diet maintained a healthy weight and did not smoke or drink excessively lived longer lives. On average, the healthier women lived 14 years longer, and the men lived 12 years longer. People who adopted no healthy habits were significantly more likely to suffer premature deaths from cardiovascular disease or cancer. 

    It is also important to note that lifespan is not the sole indicator of wellness into one’s senior years. Lifespan refers to the estimated number of years that an individual will live. ‘Health span’ is the number of years in which a person is expected to live in good health without experiencing chronic illness, disability, cognitive decline, and disease. 

    While advances in modern healthcare have improved both lifespan and health span, data suggests that the increase in lifespan has surpassed the extension of health span. This means we are living longer, but we are experiencing chronic health conditions for a more extended period towards the end of our lives.

    In this article, we will explore the science and genetics behind ageing and health span. In part 2 of this series, we’ll provide recommendations for optimising your health and protecting it as the natural ageing process occurs.

    The Science of Ageing and Longevity

    What is Ageing?

    Ageing is a natural biological process resulting from accumulating a range of cellular and molecular damages within the body. This accumulation leads to a gradual decline in mental and physical ability and a heightened risk of death from chronic disease. 

    These changes do not progress in a linear way and can take place at any age. Ageing is often linked to lifestyle and environmental factors, as well as stress, injury and traumatic events. 

    The Cellular and Molecular Mechanisms of Ageing

    On a cellular and molecular level, ageing is the accumulation of cellular damage, including DNA mutations, lesions, misfolded proteins, and impaired function of the cells, organelles, and mitochondria.

    These alterations lead to the development and accumulation of dysfunctional cells, which hinder the processes involved with the regulation of all systems within the body, known as homeostasis. This, in turn, reduces the body’s ability to repair, causing chronic and low-grade inflammation and impairing intercellular communications.

    This molecular damage, combined with:

    – Epigenetic modifications and gene expression dysregulation – turning genes on and off in our cells is not working correctly. It’s like a control system that’s supposed to manage how and when our genes do their jobs and create the correct functional molecules the body needs to function effectively, but this system is malfunctioning.

    – Impaired hormone communication – means that the system in our body that uses hormones to send messages between different parts is not working properly. Hormones are like the body’s messengers, telling different parts what to do.

    … drives the ageing process.

    The Impact of Inflammation on Ageing

    A growing body of research suggests that molecular inflammation also plays a primary role in driving the ageing process. ‘Inflamm-aging’ is the term used to describe low-grade, chronic, systemic inflammation in the context of ageing, which takes place in the absence of diagnosable infection. 

    Chronic inflammation often results from a buildup of damaged cells and molecules. When these damaged components become too numerous, the body struggles to remove them effectively. This can lead to excessive inflammation.

    Chronic inflammation continuously activates the immune system, leading to the release of inflammatory molecules and free radicals. These substances can cause oxidative stress and damage to cells, proteins, and DNA. Over time, this damage accumulates, contributing to the deterioration of tissues and organs. It can even trigger the immune system to mistakenly attack the body’s own tissues, leading to autoimmune diseases.

    It can also hinder stem cell function, which is vital for repairing and regenerating tissues. This leads to a decline in the body’s ability to maintain and replace damaged cells, further contributing to ageing.

    Inflammation in the brain, known as neuroinflammation, can cause the death of neurons and impair cognitive functions.

    Low-grade, persistent inflammation can be triggered by a wide range of factors, including unhealthy lifestyle choices such as alcohol consumption, processed food and refined sugar consumption, a sedentary lifestyle, and smoking.

    Oxidative Stress

    Free radicals are unstable molecules that can damage cells in your body. They have an unpaired electron, making them very reactive with other molecules. Reactive Oxygen Species (ROS) are free radicals that include oxygen. Both are produced naturally in your body during processes like breathing and metabolism. While they can cause cell damage, they also play a role in essential body functions, like fighting off infections. It’s important for your body to maintain a balance, as too many free radicals or ROS can lead to oxidative stress.

    Oxidative stress targets vital cellular components like DNA, fats, and proteins, leading to mutations, disruptions in cell function, and even cell death. This cellular havoc contributes significantly to the ageing process by impairing tissue repair and regeneration and disrupting normal cellular metabolism (energy production).

    As mentioned above, this oxidative damage also triggers chronic inflammation, a key factor in many age-related diseases such as atherosclerosis, diabetes, and neurodegenerative disorders like Alzheimer’s and Parkinson’s disease.

    Additionally, in the skin, oxidative stress breaks down collagen, causing wrinkles and loss of elasticity.

    The Roles of Telomeres and Telomerase in Ageing

    The tips of all DNA chromosomes feature specialised DNA bundles known as telomeres, which consist of thousands of repeated DNA sequences.

    In humans and mammals, a part of our DNA called telomeres has a specific pattern. Telomeres are like protective caps at the end of our chromosomes. They are special because they have a bit that sticks out, kind of like a tail, which looks like damaged DNA. But this tail is actually there to help protect the telomeres. In humans and some animals, this tail sticks to other parts of our DNA, forming loops that help guard the telomeres. Also, there are certain proteins at the ends of the telomeres. These proteins are important because they keep the telomeres safe and stop them from being mistakenly repaired as if they were damaged DNA.

    Telomeres shorten over time due to cell division because of the way our cells replicate their DNA. Each time a cell divides, it must copy its DNA so the new cell has a complete set. However, due to the limitations of the DNA replication process, the very ends of the chromosomes, where telomeres are located, cannot be copied entirely. This means a small portion of the telomere is lost each time the cell divides. Over many divisions, this loss adds up, and the telomeres become progressively shorter.

    When telomeres become too short, the chromosomes become vulnerable to damage and fusion with other chromosomes. This can lead to genetic instability, cell malfunction, and eventually cell ageing or cell death. The inability of very short telomeres to protect the DNA is a key factor in the ageing process at the cellular level and contributes to the overall ageing of an organism.

    As more and more cells reach this state or die, the body’s ability to regenerate and repair tissues diminishes. This gradual loss of cell function and regenerative capacity is a fundamental aspect of the ageing process.

    Cellular Senescence and Its Impacts on Ageing

    Cellular senescence is the process through which cells stop multiplying. However, these cells do not die when they technically should. Instead, they remain in the body and release compounds that trigger chronic inflammation. This action can persist over time and spread inflammation throughout the body, damaging nearby cells in the process.

    Research shows that the compounds and molecules expressed by senescent cells play critical roles throughout human lifespans and in wound healing, childbirth, and the development of embryos.

    The number of senescent cells present in the body rises with age. As the immune system becomes less effective with age too, these senescent cells accumulate. When they do, they can hinder the body’s ability to withstand illness and stress, heal from injury, and maintain healthy cognitive function. 

    Cellular senescence has been linked to a variety of age-related conditions, including cardiovascular disease, cancer, diabetes, Alzheimer’s disease, dementia, osteoporosis, and osteoarthritis. It is also connected to declines in mobility, cognitive performance, and eyesight, according to the National Institute on Aging.

    Hormonal Changes

    Hormonal changes are increasingly recognised as another key factor contributing to ageing. As we age, the balance and levels of hormones in our body change, a process often referred to as the ‘endocrinology of aging.’

    These hormonal changes can impact various bodily functions. For instance, decreasing levels of hormones like estrogen and testosterone can lead to reduced bone density, changes in skin elasticity, and muscle strength decline. This shift in hormone levels can also affect metabolism, leading to changes in body composition, such as increased fat accumulation and reduced muscle mass.

    Additionally, hormones play a crucial role in regulating mood, energy levels, and cognitive functions. Changes in hormone levels can, therefore, contribute to mood swings, fatigue, and a decline in cognitive abilities, often observed in older adults.

    Hormonal imbalances can also exacerbate other age-related conditions. For example, reduced insulin sensitivity due to altered hormone levels can increase the risk of type 2 diabetes. Similarly, changes in thyroid hormones can affect metabolic rate, impacting overall energy levels and weight.

    Moreover, hormones are integral in regulating the body’s stress response. Age-related hormonal changes can make the body less efficient at managing stress, potentially leading to increased susceptibility to stress-related health issues.

    The Role of Genetics in Longevity

    The study of the role of genes in longevity is still a developing science. Currently, it is estimated that around one quarter of the variation in human life spans is determined by genes, including APOE, FOXO3, and CETP. Not all of these genes are found in individuals with notably long life spans, but it has been theorised that variants in a range of genes – both identified and unidentified – work in synergy to promote both a long life span and a longer health span. 

    Some of the key genes that affect longevity in humans include:

    • SIRT1: The SIRT1 gene encodes the sirtuin 1 protein.
    • SIRT3: The SIRT3 gene encodes the sirtuin 3 protein.
    • SIRT6: The SIRT6 gene encodes the sirtuin 6 protein.
    • FOXO3: The FOXO3 gene encodes the forkhead box O3 protein.
    • AMPK: AMP-activated protein kinase (AMPK).

    AMPK is a type of protein that works together with three key molecules; the catalytic alpha subunit and two assistants called regulatory gamma and beta subunits. The catalytic alpha subunit leads the process, and the regulatory subunits help to ensure that the process is carried out optimally. The genes PRKAA1 and PRKAA2 create the catalytic subunit. The genes PRKAB1, PRKAB2, PRKAG1, PRKAG2, and PRKAG3 create the regulatory subunits. AMPK maintains homeostasis, regulates cellular energy usage, decreases inflammation, supports metabolic pathways and processes, and promotes autophagy and healthier ageing. 

    The mTOR gene, or mechanistic target of rapamycin, is another important factor in ageing. Research highlights mTOR as a crucial regulator of ageing and life span, as it supports cellular metabolism and integrates nutrient sensing with cellular processes responsible for cell development and proliferation. MTOR features in a variety of important cellular processes as they pertain to ageing, including nutrient sensing, autophagy, mitochondrial function and dysfunction, cellular senescence, and stem cell functioning.

    Nicotinamide adenine dinucleotide or NAD+ is a coenzyme and is thus not encoded by any specific genes. However, there are certain genes involved in its synthesis, including NAMPT (nicotinamide phosphoribosyltransferase), which is a rate-limiting enzyme in the NAD+ salvage pathway. NAD+ levels decline naturally with age, and this decline has been linked to a range of age-associated diseases, including cancer, metabolic disease, sarcopenia, and cognitive decline. 

    Research suggests that many of these diseases can be slowed or reversed by restoring NAD+ levels in the body, thus extending the human life span and health span in tandem.

    More Than Just A Biological Process

    The process of ageing is a complex series of biological interactions between cells, molecules, proteins, enzymes, genes, and external factors such as environment and lifestyle. While the rate at which we age is coded, at least to a degree, in our genetic makeup, environmental factors still play a critical role in developing or suppressing age-related conditions and diseases. 

    Ultimately, adhering to a healthy diet and lifestyle, prioritising physical activity, and limiting inflammation-causing behaviours such as alcohol consumption and smoking can slow the natural ageing process, while certain interventions such as NAD+ supplementation can improve health span and quality of life even further.