23 April, 2025
Ageing has always been a mystery, but thanks to science, we have been able to understand it more and more over the years. However, there's still a long way to go.
My name is Tilly. I am an undergraduate Biomedicine student in my final year at the UEA. Throughout my undergraduate degree, I have developed a keen interest in how a person's environment and age can affect their health and immune system. This blog aims to communicate some of the key original hallmarks of ageing and highlight the affects you don’t see, unlike wrinkles!
This question has fascinated scientists, philosophers, and skincare companies for centuries. From grey hair to bad backs, the effects of ageing are very familiar, but what is going on beneath the surface?
In this blog we shall discuss the original nine Hallmarks of ageing. The hallmarks of ageing are the processes that leave visible evidence (well visible to science) of the body starting to slow down and become less efficient. These hallmarks are predictable cellular changes that scientists have grouped into nine key categories. They act like puzzle pieces and explain why our bodies gradually lose function over time. Some are inevitable, written in our DNA, and our lifestyles influence others. Understanding these hallmarks isn’t just curiosity; it’s the key to unlocking longer, healthier lives.
Genomic instability: The DNA Dilemma
Cell replication is a lot like the children’s game of Chinese whispers. The message starts clear, but as time goes on, changes are made until it's not the same as it was at the start. This is the same in our cells; DNA damage accumulates over time due to environmental exposure, metabolic stress, and replication errors. When the errors pile up, our body's ability to repair them declines as the repair mechanisms become less effective over time, which leads to genetic mutations and an increased risk of age-related diseases, including cancer.
Telomere attrition
Telomeres are the protective caps at the ends of our chromosomes, often compared to the plastic tips on shoelaces that prevent fraying. Each time a cell divides, these telomeres shorten until eventually, they become too short for the cell to function correctly. This signals cells to stop diving or die, contributing to tissue ageing and degenerative diseases.
Epigenetic alterations
As we age, our genetic material does not just accumulate direct damage; it also changes the way it is regulated. Epigenetic modifications, such as DNA methylation and histone modifications, influence gene activity without altering the DNA sequence itself. Over time, the tight control of these modifications is lost, and epigenetic markers begin to accumulate inappropriately. It's like how actors in a play might start to improvise lines or speak out of turn, disrupting the performance. This loss of epigenetic precision can switch genes on or off at the wrong times, disturbing normal cellular functions and contributing to ageing and disease. These changes also form the basis of the "epigenetic clock," a promising way to estimate biological age.
Loss of proteostasis
Proteins are essential molecules that carry out many cell functions, from structural support to immune responses. As we age, our ability to maintain protein quality control declines, accumulating misfolded and damaged proteins. This can cause diseases such as Alzheimer’s and Parkinson’s, where toxic protein aggregates interfere with normal brain function.
Deregulated nutrient sensing
Our cells rely on complex signalling pathways to detect and respond to nutrients, however, these pathways become less efficient with age, leading to metabolic imbalances and increased risk of diabetes. Key pathways such as insulin and mTOR (mechanistic target of rapamycin) play significant roles in ageing, and research suggests that interventions like caloric restriction can improve longevity by modulating these pathways.
Mitochondrial dysfunction
Mitochondria are our cells' energy factories, converting nutrients into the power needed for cellular functions. As we age, mitochondrial efficiency declines, meaning cells struggle to meet their energy demands. This cellular fatigue can impair essential processes such as repair, regeneration, and immune responses. Over time, the reduced energy availability contributes to tissue deterioration and increases vulnerability to age-related diseases.
Cellular senescence
Senescent cells are often called “zombie cells” because they stop dividing but don’t die. Instead, they accumulate in tissues and secrete harmful inflammatory signals, damaging neighbouring cells and contributing to age-related decline. The accumulation of these cells is linked to conditions such as osteoarthritis and cardiovascular disease.
Stem cell exhaustion
Stem cells are responsible for regenerating and repairing tissues throughout our lives. However, their numbers and activity decline with age, leading to slower healing and reduced tissue maintenance. This contributes to the ageing of skin, bones, and other organs.
Altered intercellular communication
Cells constantly communicate through chemical signals to coordinate bodily functions. As we age, this communication network becomes disrupted, often due to increased inflammation. Chronic inflammation can contribute to a wide range of age-related diseases, including cardiovascular disease and neurodegeneration.
Understanding these hallmarks of ageing allows scientists to explore potential interventions to slow down or reverse aspects of the ageing process. From lifestyle choices like diet and exercise to cutting-edge research into gene therapies and senolytics (drugs that target senescent cells), the future of ageing is full of exciting possibilities. While we may still have a way to go, we are certainly getting closer to extending both lifespan and health span.
Ageing may be inevitable, but science is working to ensure we do it as gracefully as possible!
23 April 2025
By Guest Blogger