• muchlongerlife.com

Science today for a healthier tomorrow

longevity dictionary

IMPORTANT

The dictionary is intended as a tool, not a reading book. When you come across a term in an article that you do not immediately understand, you can easily look it up here for extra explanation and further insight. In this way, the dictionary supports you precisely at the moment it is needed.

It is not intended that you read the dictionary from cover to cover. The terms can be technical or complex and might therefore be off-putting if you view them out of context. Therefore, use it primarily as a reference work: targeted, practical and supportive of what you are reading at that moment.

Energy and metabolism — Genetics & regulation — Maintenance & damage — Ageing & interventions

🔋 Energy & metabolism

AMPK

AMPK is a kind of energy meter in your body. It becomes active when your cells notice that little energy is available, for example during fasting, exercise or a longer period without food.

When AMPK is activated, the body switches to a more economical and efficient mode. Processes that consume a lot of energy are slowed down, while repair and maintenance are stimulated instead.

You can view AMPK as a protective system that helps to keep cells in balance when energy is scarce.

AMPK switches your cells from energy consumption to maintenance and repair when energy is scarce.

AMPK (AMP-activated protein kinase) is an enzyme that plays a central role in cellular energy regulation. It is activated when the ratio of AMP to ATP changes — in other words, when available energy decreases.

At that moment, AMPK intervenes directly. Energy-intensive processes, such as fat and protein synthesis, are slowed down. At the same time, processes that produce energy are stimulated, such as fat burning and glucose uptake.

In addition, AMPK activates important repair mechanisms. Among other things, it stimulates autophagy, in which damaged cell components are broken down and reused.

AMPK often acts as a counterpart to mTOR. Where mTOR stimulates growth and building, AMPK focuses on maintenance, repair and efficiency.

As we age, the activity of AMPK may decrease, making cells less responsive to energy shortages.

Activation of AMPK is stimulated by exercise, calorie restriction and periods without food, among other things.

ATP (Adenosine triphosphate)

ATP is your body's direct energy source. Every cell uses ATP to function, whether it's for movement, thinking or recovery.

You can see ATP as the fuel for your cells. Without ATP, everything grinds to a halt.

The production of ATP takes place mainly in the mitochondria. The better these function, the more energy your body has available.

ATP supplies the energy every cell needs to function and repair.

ATP (adenosine triphosphate) stores energy in chemical bonds. When energy is needed, ATP is converted into ADP, releasing directly usable energy.

This energy is used for virtually all processes in the body, such as muscle contraction, the transport of substances and cell repair.

ATP is mainly produced in the mitochondria via oxidative phosphorylation. During this process, nutrients and oxygen are converted into energy.

When this process becomes less efficient, energy production drops and the load on cells increases.

Because repair and maintenance require energy, a shortage of ATP can lead to reduced cell function and faster deterioration.

Glycolysis

Glycolysis is a process by which your body makes energy from glucose, without the need for oxygen.

It is a quick way to release energy, but less efficient than energy production in the mitochondria.

When the body increasingly relies on glycolysis, this may indicate a less efficiently functioning energy system.

Glycolysis is a fast way for your body to make energy from glucose without needing oxygen.

Glycolysis is the first stage of energy production in the cell and takes place in the cytoplasm. During this process, glucose is broken down into pyruvate, producing a limited amount of ATP.

Because this process does not require oxygen, it can quickly supply energy in situations where oxygen is scarce, such as during intense exercise.

Under healthy conditions, pyruvate is subsequently processed further in the mitochondria via oxidative phosphorylation, which yields considerably more ATP.

When mitochondria function less effectively, cells switch more often to glycolysis as their primary energy source. This is also known as a metabolic shift.

This phenomenon occurs during ageing, but also in certain diseases such as cancer, where cells deliberately choose rapid but inefficient energy production (the Warburg effect).

An increased dependence on glycolysis can therefore be a signal that the cellular energy balance is becoming disrupted.

Mitochondria

Mitochondria are the powerhouses of your cells. They convert nutrients into energy (ATP), which your body needs to function.

This energy is needed for virtually everything: moving, thinking, recovering and maintaining cells. Without enough energy, these processes do not function as well.

When mitochondria function less effectively, you notice it immediately. You have less energy, recover more slowly and cells lose their balance more quickly.

You can see mitochondria as the engines of your cells — if they run less smoothly, the whole system stutters.

Mitochondria are the powerhouses of your cells and determine how much energy your body can produce.

Mitochondria convert nutrients into ATP via oxidative phosphorylation. This is the main source of energy for cells.

During this process, by-products such as free radicals are also produced. In small quantities these are normal, but when there is an imbalance they can cause damage.

As we age, the quality and number of mitochondria often decrease. This leads to less energy production and more oxidative stress.

Furthermore, damaged mitochondria are less able to renew themselves, especially when processes such as autophagy become less efficient.

Mitochondrial dysfunction is therefore seen as one of the central characteristics of ageing.

Supporting mitochondria through lifestyle, such as exercise and nutrition, can help to slow down this process.

mTOR

mTOR is a regulatory system in your body that determines whether cells focus on growth or maintenance.

When sufficient nutrition and energy are available, mTOR becomes active. It then stimulates processes such as cell growth, protein synthesis and cell division.

This is important for recovery and building. However, when mTOR remains active for a prolonged period, maintenance and cleanup processes get less opportunity.

mTOR puts your body into “growth mode”, but if that setting stays on for too long, the system gets out of balance.

mTOR is the system that determines whether your body focuses on growth and building or on repair and maintenance.

mTOR (mechanistic Target Of Rapamycin) is a central regulatory mechanism that responds to signals such as nutrients, energy and growth factors. It acts as a switch that determines whether the cell focuses on growth or maintenance.

When mTOR is active, it stimulates processes such as protein synthesis, cell growth and cell division. This is essential for recovery, muscle building and normal development.

At the same time, an active mTOR status inhibits processes such as autophagy — the clearing and recycling of damaged components within the cell. This creates a clear balance between growth and maintenance.

In an environment with constant food intake and few periods of scarcity, mTOR can remain chronically active. As a result, cells remain in “build mode”, while repair processes run less efficiently.

In the long term, this can contribute to the accumulation of damage in cells, which plays a role in ageing and disease.

mTOR works closely with other systems, such as AMPK. Where mTOR stimulates growth, AMPK becomes active during energy shortages and puts the cell into maintenance mode. The balance between these systems is essential for health.

NAD⁺ (Nicotinamide Adenine Dinucleotide)

NAD⁺ is a substance found in every cell of your body that is essential for energy production and repair.

It helps your mitochondria to make energy and plays a role in repairing damaged DNA.

As you get older, NAD⁺ levels drop. This affects energy, recovery, and cellular health.

Without sufficient NAD⁺, cells can produce less energy and repair themselves less effectively.

NAD⁺ is an essential substance that your cells need for energy production and repair.

NAD⁺ is a coenzyme involved in hundreds of processes within the cell, particularly in energy production and repair. It plays a central role in the mitochondria, where it aids the conversion of nutrients into ATP.

Additionally, NAD⁺ is essential for the function of sirtuins, a group of proteins involved in DNA repair, anti-inflammation and the regulation of metabolism.

As we age, the amount of NAD⁺ in the body decreases. As a result, energy production and repair processes become less efficient, which can lead to fatigue and the accumulation of damage in cells.

Factors such as chronic stress, poor nutrition and inflammation can accelerate this decline. This creates a vicious circle: less NAD⁺ leads to poorer recovery, which in turn places additional strain on the system.

Because NAD⁺ plays such a central role in multiple processes simultaneously, it is seen as a key link in ageing.

Oxidative phosphorylation

Oxidative phosphorylation is the process by which your body makes energy (ATP) in the mitochondria.

This uses oxygen to convert nutrients into energy. This is the main way your body produces energy.

When this process works less well, you have less energy and more damage occurs in cells.

It is the moment when oxygen is converted directly into usable energy for your body.

Oxidative phosphorylation is the process by which your cells use oxygen to produce energy (ATP).

Oxidative phosphorylation takes place in the mitochondria and is the final and most efficient component of energy production in the cell.

During this process, energy from nutrients and oxygen are combined to make ATP, the primary energy source for cells.

This happens via a series of steps in which energy is gradually passed on and ultimately used to produce ATP.

Oxygen plays a crucial role in this. Without oxygen, this process cannot continue and energy production largely comes to a halt.

During this process, by-products such as free radicals are also produced. In small amounts these are normal, but if disrupted they can cause damage to cells.

As we age, the efficiency of this process often decreases. As a result, less energy is produced and oxidative stress increases.

Because this process is so central to energy production, a disruption directly affects the functioning of cells.

Genetics & regulation

DNA

DNA is the blueprint of your body. It contains all the information that determines how your cells function, grow and repair.

Every cell contains the same DNA, but not all parts are active. Which genes are switched on or off determines how your body behaves.

Over time, DNA becomes damaged. This is a normal process, but the accumulation of damage plays a major role in ageing.

DNA contains the genetic information that determines how cells function, and damage to this plays a central role in ageing and disease.

DNA consists of long chains of genetic information stored in the cell nucleus. This information directs the production of proteins, which carry out virtually all processes in the body.

Every day, DNA damage occurs due to internal processes, such as energy production, and external influences, such as radiation, diet and toxins. The body has extensive repair systems to repair this damage.

As people age, the efficiency of these repair systems decreases. As a result, errors persist and accumulate. This can lead to poorly functioning cells or uncontrolled cell division.

DNA damage plays a role in virtually all ageing processes, including cancer, cellular senescence and the loss of organ function.

Protecting DNA and supporting repair mechanisms is therefore seen as an important part of healthy ageing.

DNA methylation

DNA methylation is a process that determines whether genes are switched on or off. It does not change your DNA itself, but how it is used.

You can see it as a sort of switch system that controls which information is read.

This process changes throughout your life and is influenced by your lifestyle.

DNA methylation acts like a switch that determines which genes are active, without altering the DNA code itself.

In DNA methylation, small chemical groups (methyl groups) are added to specific parts of the DNA. As a result, certain genes become less active or are switched off completely.

This mechanism is part of epigenetics: the regulation of gene activity without altering the genetic code itself.

Patterns of DNA methylation change throughout life and are influenced by factors such as diet, stress, sleep, and exposure to toxins.

Because these changes occur relatively predictably, they are used to measure biological age using so-called epigenetic clocks.

Disruptions in DNA methylation are linked to various diseases, including cancer and metabolic disorders.

DNA repair

DNA repair is the process by which your body repairs damaged DNA. This happens continuously, as damage occurs daily.

Without this system, errors would quickly accumulate and cause problems.

A well-functioning DNA repair system is essential for keeping cells healthy.

DNA repair ensures that damage in your DNA is continually repaired, allowing cells to continue functioning healthily.

Your body possesses multiple repair mechanisms that can repair various forms of DNA damage, such as damage caused by oxidative stress, radiation, or errors during cell division.

These systems recognise damage and repair it by targeted DNA cutting, correction and reconstruction.

As people age, the efficiency of DNA repair decreases. As a result, errors persist longer and can accumulate.

This can lead to a loss of cell function, an increased risk of cancer and the acceleration of ageing processes.

DNA repair is highly dependent on sufficient energy, properly functioning enzymes and a healthy balance within the cell.

Epigenetics

Epigenetics is about how your genes are used, not your DNA itself.

You can see it as a kind of regulatory system that determines which genes are switched on and which are off. After all, not all the information in your DNA is used all the time.

Your lifestyle has a major influence on this. Factors such as diet, exercise, stress and sleep can determine how your genes behave.

Epigenetics determines which genes are switched on or off, thereby forming the link between your DNA and your lifestyle.

Epigenetics encompasses all processes that determine which genes are active and which are not, without the DNA code itself changing. It is therefore not about the content of your DNA, but about how that information is used.

This occurs via mechanisms such as DNA methylation and changes in proteins surrounding the DNA (histones). These determine how accessible certain parts of the DNA are, and therefore whether a gene is “switched on” or alternatively switched off.

This allows cells to adapt to their environment. Depending on signals such as nutrition, stress or exercise, different genes become active, causing the body to react and function differently.

Factors such as lifestyle play a major role in this. Diet, sleep, exercise and stress continually influence how genes are read and used.

As we age, these epigenetic patterns can become less stable. Genes that should actually be switched off remain active, or vice versa. This can contribute to disruptions in cells and ultimately to ageing and disease.

Epigenetics thus forms the link between your genetic makeup and your lifestyle. It shows that your genes are not fixed in how they are expressed, but that your body is constantly adapting to how you live.

epigenetic clock

The epigenetic clock is a way to measure how old your body is biologically.

Instead of looking at your age in years, this method looks at changes in your DNA, specifically DNA methylation. This provides insight into how your cells behave and how quickly they are ageing.

This allows you to see whether your body is functioning “younger” or “older” than your actual age.

Your chronological age says how many years you have lived, but the epigenetic clock shows how your body is actually doing.

The epigenetic clock measures how biologically old your body is based on changes in your DNA.

The epigenetic clock is based on specific patterns of DNA methylation that change as you get older. These patterns are relatively predictable and are therefore used as a biomarker for ageing.

By analysing these methylation patterns, an estimate of your biological age can be made. This is done by looking at which parts of the DNA are active and how this activity changes.

What makes this method special is that the outcome can differ from your chronological age. Someone can be biologically younger or indeed older than the number of years they have lived.

These differences are influenced by factors such as diet, exercise, stress, sleep and inflammation levels. The epigenetic clock therefore responds directly to lifestyle and environment.

Therefore, this method is widely used in ageing research and interventions that could potentially slow down this process.

Crucial is that the epigenetic clock is not a fixed given. Because epigenetic patterns can change, biological age can also adapt to a certain extent.

Gene expression

Gene expression determines which genes in your body are active and which are not. Although you have the same DNA in every cell, that does not mean all genes are always “switched on”.

You can see it as a kind of control panel. Depending on what your body needs, certain genes are activated or deactivated.

This process is heavily influenced by your lifestyle. Diet, exercise, stress and sleep partly determine how your genes behave.

Gene expression converts the information in your DNA into proteins that determine how your body functions.

Gene expression is the process by which the information in your DNA is converted into proteins. These proteins control virtually all functions in the body, from metabolism to repair and defence.

The process begins with transcription, whereby a piece of DNA is copied into RNA. Next, this RNA is translated into a protein with a specific function.

Not all genes are continuously used. Cells determine which genes are needed based on signals from their environment. This allows different cell types, such as muscle and brain cells, to have completely different functions despite identical DNA.

Gene expression is regulated by epigenetic mechanisms, such as DNA methylation and histone modification. These determine how accessible certain parts of the DNA are.

Disruptions in gene expression can lead to faulty protein production, which plays a role in ageing and diseases such as cancer and neurodegeneration.

Good regulation of gene expression is therefore essential for balance and health.

Sirtuins (SIRT1–SIRT7)

Sirtuins are proteins that play an important role in the maintenance and repair of your cells. They help to limit damage and keep processes running efficiently.

They become especially active when less energy is available, for example during fasting or intense exercise. In such situations, the body switches from growth to maintenance.

Sirtuins work closely with NAD⁺, a substance required to produce energy and direct repair processes.

Sirtuins are proteins that regulate cell maintenance, repair and energy use.

Sirtuins (SIRT1–SIRT7) form a group of seven proteins, each with a specific role within the cell. They are located in various places, such as the cell nucleus, the cytoplasm and the mitochondria.

Their main function is the regulation of cell maintenance. They support DNA repair, inhibit inflammation and help to adapt the cell's energy metabolism. They do this by influencing other proteins through a process called deacetylation.

An important feature is that sirtuins are dependent on NAD⁺. As a result, their activity is directly linked to the energy status of the cell. When NAD⁺ levels rise — for example during energy deficiency — sirtuins become more active.

They thus function as a switching point between energy, repair and survival. They help cells to deal more efficiently with stress and damage.

As people age, NAD⁺ levels often decline, which also reduces sirtuin activity. This can contribute to less effective repair and more disruptions in cells.

Sirtuins work together with systems such as AMPK and mTOR and form part of the broader network that determines whether a cell focuses on growth or maintenance.

🧹 Maintenance & damage

Apoptosis

Apoptosis is the process by which your body neatly clears away old or damaged cells. It is a controlled form of cell death that prevents bad cells from accumulating.

Instead of a cell “breaking”, it breaks itself down in a controlled manner. This happens without damage to surrounding tissue.

This process is essential for keeping your body healthy. Without apoptosis, defective cells persist, which can cause problems.

Apoptosis ensures that damaged cells are safely removed before they can cause harm.

Apoptosis is a tightly regulated biological process in which cells switch themselves off when they no longer function properly. This occurs via internal signals that initiate a controlled breakdown.

During this process the cell shrinks, the DNA is chopped into pieces and the remnants are tidily cleared away by other cells. Because this happens without an inflammatory response, surrounding tissue remains intact. This distinguishes apoptosis from damaging processes such as necrosis.

Apoptosis plays a crucial role in preventing cancer. Cells with DNA damage are removed in time before they can divide uncontrollably.

Apoptosis is also indispensable for the normal renewal of tissues. It ensures a continuous balance between new and old cells.

When this process functions less effectively, damaged cells can persist. This can contribute to ageing, inflammation and the development of disease.

Autophagy

Autophagy is your cells' cleaning and recycling system. Damaged or worn-out parts are broken down and reused.

This keeps cells functioning healthily and efficiently. It prevents waste from accumulating and disrupting processes.

You can view autophagy as an internal maintenance system that is continually working to keep your cells in good condition.

Autophagy ensures that damaged components are cleared away and recycled, keeping cells functioning healthily and efficiently.

Autophagy is an essential process by which cells maintain themselves and protect against damage. When cellular components, such as proteins or mitochondria, become damaged, they are recognised and enveloped in special vesicles, known as autophagosomes.

These vesicles then fuse with lysosomes, where enzymes break down the material into small building blocks. These building blocks are subsequently reused for energy production or for constructing new cell structures.

Because of this, autophagy is not only a clearing process, but also an efficient recycling system. Instead of storing waste, the cell reuses what is still usable.

Autophagy becomes particularly active when the body is under stress, for example during a shortage of energy or nutrients. In such situations, the cell switches from growth to maintenance and optimisation.

As we age, the efficiency of autophagy often decreases. As a result, damaged components persist for longer, which can lead to disruptions and loss of function.

Furthermore, autophagy plays a role in preventing disease. When defective components are not removed in time, they can contribute to inflammation and damage to surrounding cells.

Autophagy is directly connected to other important processes, such as energy production (ATP), mitochondrial function and systems such as mTOR and AMPK. Together, these determine how well a cell can maintain itself.

Chronic inflammation

Chronic inflammation is a low-grade, ongoing inflammatory response in your body. You usually don't notice it immediately, but it is continuously present.

Unlike an acute inflammation (such as with a wound), this form does not go away by itself. It remains active in the background and constantly burdens your body.

In the long term, this can cause damage to cells and tissues. Therefore, chronic inflammation is seen as a major factor in ageing.

Chronic inflammation keeps the body continuously in a low-grade state of inflammation, causing damage to accumulate and accelerating ageing.

Chronic low-grade inflammation, also known as inflammaging, occurs when the immune system remains mildly activated for a prolonged period. This can be caused by factors such as stress, being overweight, an unhealthy diet, lack of sleep and ageing itself.

Instead of a short, targeted response (such as with an infection), the body continuously produces small amounts of inflammatory substances, such as cytokines. These substances are useful in the event of an acute threat, but harmful when they remain present for a long time.

This constant activation causes cells to damage more quickly. It affects blood vessels, the brain, muscles and organs among other things, thereby increasing the risk of diseases such as cardiovascular disease, diabetes and neurodegenerative disorders.

Additionally, chronic inflammation disrupts other important processes, such as insulin sensitivity, mitochondrial function and cell repair. This creates a vicious circle: damage leads to inflammation, and inflammation leads to more damage.

Reducing chronic inflammation is strongly linked to lifestyle. Diet, exercise, sleep and stress management play a central role in this.

Inflammageing

Inflammaging is chronic, low-grade inflammation specifically associated with ageing.

It is a silent form of inflammation that is often present for years without clear symptoms.

This ongoing inflammatory activity contributes to damage in the body and accelerates ageing.

Inflammageing is chronic, low-grade inflammation that slowly damages your body and accelerates ageing.

Inflammaging occurs because the immune system changes with age. It reacts less effectively to real threats, but at the same time remains continuously mildly activated.

As a result, inflammatory substances, such as cytokines, remain in circulation for a prolonged period. This causes a constant strain on cells and tissues.

Inflammaging plays a role in many age-related conditions, including cardiovascular diseases, diabetes and neurodegenerative diseases.

It is exacerbated by factors such as senescent cells, gut problems and metabolic dysregulation.

Inflammaging is therefore not isolated, but forms part of a larger network of processes that mutually reinforce one another.

Oxidative stress

Oxidative stress occurs when there are more free radicals in the body than it can neutralise.

These substances are reactive and can damage cells, proteins and DNA.

You can see it as a form of “rust” in your body. When this process becomes unbalanced, it contributes to ageing and disease.

The problem is not the presence of free radicals themselves, but the disruption of the balance.

Oxidative stress occurs when the balance between free radicals and antioxidants is disrupted.

Free radicals are unstable molecules that are produced during normal processes, such as energy production in the mitochondria. They also play a role in signalling processes in the body.

The body has antioxidants that neutralise these substances. As long as there is a good balance, the system remains stable.

When too many free radicals are produced or too few antioxidants are available, oxidative stress occurs. This leads to damage to important structures in the cell, such as proteins, fats and DNA.

This damage can accumulate when the capacity for repair is insufficient. This plays an important role in ageing and the onset of chronic diseases.

Factors such as smoking, poor diet, chronic stress and pollution can disrupt this balance.

Oxidative stress does not stand alone, but is closely linked to processes such as mitochondrial dysfunction, inflammation and impaired cell repair.

proteostasis

Proteostasis is the system that ensures proteins in your body are properly made, folded and cleared away.

Proteins must have a specific shape in order to function properly. When they are misfolded, they cannot do their job or may even cause damage.

You can view proteostasis as a quality control: properly functioning proteins stay, faulty proteins are refolded, repaired or removed.

When this control falters, damaged proteins accumulate and cells become unbalanced.

Proteostasis is your cell's quality control system: it ensures that proteins are correctly made, folded and cleared away on time.

Proteostasis (protein homeostasis) encompasses all processes that ensure a healthy protein balance within the cell. This begins with the synthesis of proteins, followed by their correct folding into a functional structure.

Special proteins, known as chaperones, guide this folding process and prevent proteins from misfolding. When proteins do become damaged or misfolded, they are recognised and degraded via systems such as the proteasome and autophagy.

This clearance system is essential, because otherwise faulty proteins accumulate and clump together. These accumulations disrupt the functioning of cells and are linked to ageing and various diseases.

With ageing, the efficiency of proteostasis decreases. Damaged proteins are less effectively repaired or removed, which increases the burden on the cell.

Proteostasis is directly linked to other processes, such as autophagy, energy production and cellular stress responses. When these systems become unbalanced, it directly affects protein quality and therefore the health of the cell.

🧓 Ageing & interventions

biological age

Biological age says something about how well your body functions, not how many years you have lived.

Two people of the same age can be biologically very different. One still functions as “young”, while the other already shows signs of decline.

Your biological age is influenced by factors such as diet, exercise, stress, sleep and the extent to which your body can repair damage.

Biological age shows how well your body actually functions, regardless of the number of years you have lived.

Biological age is a way of looking at the actual condition of the body. Instead of just counting how many years someone has lived, it looks at how well cells, tissues and organs function.

At a cellular level, various processes play a role. Think of DNA damage, energy production in mitochondria, inflammation levels, and the ability of cells to repair themselves. Together, these determine how “old” your body actually is.

When these systems function properly, cells continue to work efficiently and the body is better able to cope with damage. If these processes deteriorate, damage accumulates and biological age increases — regardless of chronological age.

There are several ways to measure biological age. One of the best-known methods is via epigenetic changes, such as DNA methylation. This can be used to estimate how fast someone is ageing on a biological level.

The difference between biological and chronological age can be significant. This makes it a valuable indicator of health and disease risk, as it shows how the body is truly faring.

What is important is that biological age is not a fixed given. Because it is strongly influenced by lifestyle and environmental factors, it can change to a certain extent. That also makes it a practical and motivating concept within health and prevention.

Cellular senescence (zombie cells)

Cellular senescence means that cells stop dividing, but are not cleared away. They remain, as it were, “stuck” in the body.

Instead of becoming quiet, these cells remain active. They release substances that can disrupt surrounding healthy cells and cause inflammation.

You can see them as cells that have lost their function, but stick around and negatively affect their environment. That is why they are also sometimes called zombie cells.

Senescent cells accumulate in the body and disrupt their environment, thereby contributing to inflammation and ageing.

When a cell sustains too much damage — for example through DNA damage or stress — the body basically has two options: repair the cell or clear it away via apoptosis. But sometimes neither happens. The cell stops dividing, but continues to exist. We call this senescence.

Senescent cells are not passive. They actively secrete substances, such as inflammatory signals, growth factors and enzymes that can break down tissues. This whole is called the SASP profile (senescence-associated secretory phenotype).

These substances affect surrounding healthy cells. They can cause damage there, trigger inflammation and even prompt other cells to undergo senescence. This creates a kind of chain reaction in tissues.

In young, healthy bodies, these cells are usually cleared away in time by the immune system. But as we age, this clearance capacity decreases. As a result, senescent cells accumulate.

This accumulation is associated with tissue loss of function, chronic inflammation and the onset of age-related diseases.

Senescent cells are therefore regarded as a key target in ageing research.

Hallmarks of ageing

The “hallmarks of aging” are the main biological processes that cause ageing.

Scientists have identified a number of core mechanisms that together explain why and how we age.

By understanding these processes better, it becomes possible to influence ageing in a more targeted way.

The hallmarks of aging are the main biological processes that together determine how and why we age.

The hallmarks of ageing form a scientific framework that describes the primary drivers of ageing. Examples of these include DNA damage, loss of proteostasis, mitochondrial dysfunction and chronic inflammation.

Each of these processes contributes in its own way to the deterioration of cells and tissues. Together they reinforce each other, accelerating ageing.

In this way, DNA damage can lead to dysfunctional cells, which in turn produce inflammatory substances. This inflammation then causes additional damage to other cells.

The model helps to see ageing not as a single process, but as a coherent network of biological changes.

Many new therapies focus on one or more of these hallmarks, with the aim of slowing down ageing and improving health.

NMN (Nicotinamide Mononucleotide)

NMN is a substance that the body uses to produce NAD⁺.

It therefore indirectly plays a role in energy production and cell repair.

The amount of NMN in the body decreases with age.

NMN is not energy itself, but a building block that helps to support energy processes.

NMN is a building block your body uses to produce NAD⁺ to support energy and recovery.

NMN is a precursor to NAD⁺ and is converted into this important coenzyme in the body. As a result, it plays a role in processes related to energy and repair.

As NAD⁺ levels decline with age, research is being conducted into whether increasing NMN can help support these systems.

Animal studies show that increasing NAD⁺ via NMN can influence certain ageing processes.

Research in humans is still ongoing. The initial results point to potential effects on energy balance and metabolism.

It is important to approach this realistically: the insights are promising, but not yet definitively proven.

NR (Nicotinamide Riboside)

NR is, just like NMN, a precursor to NAD⁺.

It helps the body to increase NAD⁺ levels, thereby supporting energy and recovery.

NR is well absorbed and has been investigated in human studies.

NR is not energy itself, but a building block that helps to support energy processes.

NR is a building block that the body uses to make NAD⁺ and thereby support energy and recovery.

NR (nicotinamide riboside) is a precursor to NAD⁺ and is converted in the body via a different pathway than NMN. It therefore plays a role in processes related to energy and recovery.

Because NAD⁺ levels decline with age, research is being conducted into whether increasing NR can help support these systems.

Human studies show that NR can be effectively absorbed and can increase NAD⁺ levels.

The effects on health and ageing are still being investigated. The initial results indicate potential improvements in energy management and metabolism, but are not yet definitive.

Just like with NMN, it is not a direct energy source, but a building block that the body uses within existing systems.

Rapamycin

Rapamycin is a substance that affects the mTOR system in your body, an important regulatory system for growth and cell activity.

By inhibiting mTOR, the body temporarily shifts from a state of growth to a state of maintenance and repair.

In animal studies, rapamycin is linked to effects on ageing processes, but in humans research is still very much ongoing.

Rapamycin inhibits the mTOR pathway and shifts the body from growth to repair and maintenance.

Rapamycin was originally developed as a drug with immunosuppressive properties and is used, amongst other things, in organ transplants to prevent rejection. It works by inhibiting mTOR, a central regulatory system that responds to nutrients, energy, and growth signals.

mTOR regulates processes such as protein synthesis, cell growth and cell division. When this system is active, the body is in an anabolic state. This is essential for recovery and development, but with continuous activation, maintenance processes can be pushed into the background.

By inhibiting mTOR, the body shifts towards maintenance and repair. A major effect of this is the stimulation of autophagy, whereby damaged cellular components are cleared away and recycled.

Animal studies have shown that inhibition of mTOR via rapamycin can influence lifespan and healthspan. This has led to a great deal of interest within ageing research.

In humans, this picture is less clear. The long-term effects, optimal dosage and safety are still being researched. Rapamycin can also have side effects, such as disruption of the immune system and metabolism.

The principle behind rapamycin aligns with a broader biological mechanism: the balance between growth and maintenance. In an environment of constant abundance, that balance can shift towards the chronic activation of growth systems.

Rapamycin demonstrates how strongly this balance is biologically regulated — and how that influences ageing.

Resveratrol

Resveratrol is a substance found in, among other things, grapes and red wine. It belongs to a group of substances known for their protective properties.

It is being investigated for potential effects on cell protection and ageing, particularly on processes such as inflammation and energy regulation.

You can see it as a signalling molecule that helps the body respond to stress and damage, although the effect in humans is not yet fully clear.

Resveratrol appears to activate certain protective mechanisms in cells, but evidence in humans is still limited.

Resveratrol is a plant compound that may support protective processes in cells.

Resveratrol is a polyphenol, a plant compound produced by plants as protection against stress, such as UV radiation or infections. In the human body, research is being conducted to see whether this substance might have similar protective effects.

An important point of attention is the potential influence on sirtuins, proteins involved in DNA repair, anti-inflammation and energy management.

In addition, resveratrol appears to play a role in reducing oxidative stress and inflammatory processes, both important factors in ageing.

One challenge is the low bioavailability: the body absorbs resveratrol relatively poorly, meaning that the effect in practice may be limited.

Although laboratory and animal studies show interesting results, the evidence in humans is not yet convincing. Therefore, resveratrol is seen as a promising, but not a proven intervention.

Senolytics

Senolytics are substances aimed at clearing out senescent cells, also known as zombie cells.

These are old or damaged cells that no longer function properly, but stick around in the body.

These cells disrupt their environment by releasing inflammatory substances and contribute to ageing and loss of tissue function.

By selectively removing these cells, the body can function better again and space is created for healthier cells.

Senolytics are substances that selectively clear damaged, senescent cells.

Senolytics represent a relatively new area of research within the biology of ageing. They specifically target senescent cells, which accumulate as we get older.

Normally, damaged cells are cleared away via processes such as apoptosis. However, senescent cells often escape this. They remain actively present and produce inflammatory substances, growth factors and enzymes that can damage surrounding cells.

Senolytics tackle this issue by selectively switching off these cells. They exploit vulnerabilities in senescent cells, making them more sensitive to certain signals than healthy cells.

In animal studies, the removal of senescent cells has led to improvements in physical functions, such as muscle strength, organ function and recovery capacity. In some cases, an extension of lifespan was also observed.

In humans, this research is still at an early stage. The long-term effects, safety and effectiveness are still being investigated.

The idea behind senolytics fits within a broader approach to ageing: not just preventing damage, but also actively clearing away existing damage.

Stem cells

Stem cells are special cells that can develop into different types of cells in the body. They form the basis for the repair and renewal of tissues.

When damage occurs, for example in muscles, skin or organs, stem cells can create new cells to repair this.

As we age, both the number and quality of stem cells decrease. As a result, it becomes increasingly difficult for the body to repair itself properly.

Stem cells are cells that can renew themselves and develop into specialised cells for repair and renewal.

Stem cells play a central role in the maintenance of the body. They have two unique properties: they can continually renew themselves and develop into specialised cells, such as muscle, skin or blood cells.

This makes them essential for regeneration. In healthy conditions, stem cells replace damaged or worn-out cells, keeping tissues functioning properly.

There are several different types of stem cells. Some can develop into many different cell types, while others are more specific and mainly support one type of tissue.

As people age, this system changes. Stem cells respond less well to signals, divide less often and differentiate less efficiently. Their environment — the stem cell niche — also becomes imbalanced.

As a result, the body's capacity for repair gradually declines. Minor damage is repaired less effectively and tissues lose their resilience.

Stem cells depend on other processes in the body. Energy supply (ATP), the level of inflammation, and signals from systems such as mTOR and sirtuins partly determine how well they function.

When these systems fall out of balance, it directly affects the quality of stem cells and the body's ability to regenerate.

Telomeres

Telomeres are protective ends of your DNA. You can compare them to the plastic tips of a shoelace that prevent it from fraying.

They protect your DNA during cell division. Without this protection, important genetic information would be damaged.

Every time a cell divides, telomeres become a little shorter. This is a normal process, but has long-term consequences.

Telomeres protect your DNA during cell division and determine how often a cell can safely renew itself.

Telomeres are located at the end of chromosomes and consist of repeating pieces of DNA. They have no direct function, but are essential as a protective mechanism.

During DNA replication, the end of a chromosome cannot be fully replicated. Telomeres compensate for this by acting as a buffer. With each division, a small piece of the telomere is sacrificed instead of functional DNA.

Over time, telomeres become progressively shorter. When they reach a critical length, a cell can no longer safely divide. At that point, the cell stops dividing or is cleared away.

This mechanism is often seen as a biological clock. It determines how many more times a cell can divide and thus plays a role in ageing.

Telomere length is influenced by factors such as stress, inflammation and oxidative damage. These can accelerate the shortening process.

Telomeres do not stand alone, but are connected to processes such as DNA repair, cellular ageing and inflammation. When they become too short, the likelihood of cells functioning less well increases.

Here comes the summary