2.3. Explain the ageing process at the cellular level

This guide will help you answer 2.3. Explain the ageing process at the cellular level.

The ageing process is complex and occurs throughout the body, impacting every system and cell. Understanding what happens at the cellular level helps explain why ageing leads to physical, mental, and functional changes over time. The changes in cells as we age are influenced by both internal factors (like genetics) and external factors (such as lifestyle, diet, and environmental exposure). These contribute to the gradual decline in how our body’s cells function and repair themselves.

This guide will go into the main cellular processes involved in ageing, explain what changes occur, and how these affect the overall ageing process.

Cellular Senescence

Cellular senescence is a key factor in ageing. This term means that cells have stopped dividing but are still metabolically active. Human cells can only divide a limited number of times during their lifespan, often referred to as the “Hayflick limit.” After this point, cells become senescent.

Senescent cells build up in tissues as we age. They release harmful substances called inflammatory cytokines, chemokines, and reactive oxygen species (ROS). These substances can damage nearby healthy cells and tissues. This chronic low-level inflammation caused by senescent cells is sometimes called “inflammaging.”

Senescent cells are also resistant to programmed cell death (apoptosis). This means they stay within the body, even though they are no longer contributing positively to its function.

Key points about cellular senescence include:

• Limits on how many times a cell can divide
• Release of harmful substances contributing to inflammation
• Resistance to apoptosis, leading to their accumulation in tissues

DNA Damage and Repair

DNA contains the genetic instructions that control a cell’s function and ability to reproduce. Over time, damage to DNA accumulates. This can happen due to external factors like UV radiation, smoking, and pollution, or internal factors like normal metabolic activities.

Cells have mechanisms to repair damaged DNA, but these systems become less effective with age. When DNA damage isn’t repaired properly, it can lead to mutations or dysfunction in the cell. In some cases, DNA damage can cause cells to become senescent or develop into cancerous cells.

As we age, the following occur with DNA:

• DNA damage happens more frequently
• DNA repair mechanisms work less efficiently
• Unrepaired DNA affects cell function and increases the risk of diseases, including cancer

Telomere Shortening

Telomeres are protective caps at the ends of chromosomes. They prevent DNA strands from fraying or sticking to each other during cell division. Each time a cell divides, its telomeres get shorter. When telomeres become too short, the cell can no longer divide properly and becomes senescent or dies.

Telomere shortening is often used as a signal of cellular ageing. Factors such as stress, poor diet, and lack of exercise can accelerate telomere shortening.

Key facts about telomeres include:

• Telomeres protect chromosomes
• Shortening occurs with each cell division
• When telomeres are too short, cells lose their ability to divide

Mitochondrial Dysfunction

Mitochondria are often called the “powerhouses” of cells because they generate energy. This energy is in the form of a molecule called ATP (adenosine triphosphate). However, as people age, mitochondrial function declines. At the same time, mitochondria produce more reactive oxygen species (ROS), which are damaging molecules.

Over time, this increased oxidative stress can harm cells and tissues. It also contributes to inflammation, cell damage, and the overall decline in organ function.

Key aspects of mitochondrial dysfunction during ageing include:

• Decreased energy production (ATP)
• Increased production of damaging reactive oxygen species
• Greater damage to cells and tissues

Accumulation of Cellular Waste

Cells naturally produce waste as part of their regular functions. Autophagy is the process by which cells clear out damaged or unnecessary components. This helps maintain healthy cell function. However, autophagy becomes less efficient with age, which leads to an accumulation of cellular waste.

One specific type of waste that builds up with ageing is called lipofuscin. Lipofuscin is made up of damaged proteins, fats, and other cellular materials that the cell cannot break down or expel. This waste builds up inside the cell and disrupts normal functions.

Summary of cellular waste as part of ageing:

• Less efficient autophagy
• Build-up of waste materials like lipofuscin
• Disruption of normal cell processes

Epigenetic Changes

Epigenetics refers to changes in gene expression without altering the DNA sequence itself. These changes are controlled by chemical markers that regulate how genes are turned “on” or “off.” Over time, the epigenetic markers on DNA are modified, which may result in genes being activated or silenced incorrectly.

For example, certain genes that prevent cancer or repair DNA may be switched off with age. This increases the risk of dysfunction and disease.

Epigenetic changes include:

• Increasing mistakes in how genes are regulated
• Activation of harmful genes or silencing of beneficial ones
• Greater susceptibility to age-related conditions

Loss of Stem Cell Function

Stem cells are undifferentiated cells that can become specialised cells. They play a critical role in tissue repair and regeneration. As the body ages, the number of functioning stem cells decreases. This impacts the body’s ability to repair damage and replace ageing or dead cells.

The decline in stem cell function is a major reason why tissues take longer to heal and regenerate in older adults.

Key points on stem cell decline:

• Fewer functional stem cells available for tissue repair
• Slower healing and regeneration of tissues
• Reduced ability for the body to recover from damage

Impact of Oxidative Stress

Oxidative stress happens when there’s an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to neutralise them with antioxidants. ROS are damaging molecules that can attack cellular structures, including DNA, proteins, and lipids. This leads to cellular damage.

Ageing increases oxidative stress because mitochondrial function declines, while the body’s antioxidant defences become weaker.

Main features of oxidative stress in ageing:

• Increased production of damaging reactive oxygen species
• Decline in antioxidant defence systems
• Damage to DNA, proteins, and cell membranes

Reduction in Protein Quality Control

Proteins are essential molecules that perform various functions in the cell. They need to be correctly folded and properly maintained to work. Cells have systems in place to identify and either fix or remove damaged proteins. This is called protein quality control.

With age, this system becomes less effective. Damaged or misfolded proteins build up and can form aggregates. This disrupts cellular function and has been linked to age-related diseases like Alzheimer’s and Parkinson’s.

Key facts about protein quality control include:

• Reduced ability to manage damaged proteins as we age
• Accumulation of misfolded proteins
• Association with neurodegenerative and other age-related diseases

How Cellular Changes Affect the Body

The cellular changes described above slowly cause tissues and organs to work less efficiently. This impacts different systems in the body, including:

• Immune System – Senescent cells cause chronic inflammation. The immune system becomes weaker, making it harder to fight infections.
• Muscle and Skeletal System – Reduced stem cells and mitochondrial dysfunction lead to muscle loss and bone fragility.
• Skin – Collagen production decreases, leading to thinner and less elastic skin.
• Brain – Accumulation of damaged proteins and reduced repair mechanisms lead to slower cognitive function and higher risk of diseases like dementia.

These changes also lead to increased vulnerability to diseases such as cancer, diabetes, cardiovascular disease, and neurodegenerative disorders.

Conclusion

The ageing process at the cellular level is driven by a combination of senescence, telomere shortening, DNA damage, mitochondrial dysfunction, and more. These changes directly impact the function of cells and organs, contributing to the visible and invisible signs of ageing. Understanding these processes provides valuable insight into how ageing occurs and how it affects overall health in later life.