The biology of ageing: what we know and what we don't know

10 days ago

Die Biologie des Alterns: Was wir wissen und was nicht

10 days ago

Aging affects us all. But what exactly happens in our bodies when we age? And even more exciting: can we slow down or even reverse this process? In recent years, science has provided many new insights. At the same time, leading experts show how complex and controversial many of today's approaches still are.

What is considered certain today: aging is not a fixed process, but a biological process that can in principle be influenced. Nevertheless, not every new theory is automatically reliable or clinically relevant. A healthy dose of scepticism is particularly needed when it comes to much-discussed topics such as age clocks, epigenetic reprogramming or senolytics. This article will give you a well-founded overview of what has been scientifically proven, which concepts should be viewed critically and what you can take away from this for your everyday life.

Between hope and hype

We have put together a very exciting longevity roundtable discussion, which featured four of the most renowned experts in the field: Steven Austad, Matt Kaeberlein, Richard Miller and host Peter Attia. These experts have been studying the question of why we age and what can possibly be done about it for decades.

And now to the crux of this roundtable discussion: there is still no universally accepted scientific definition of aging. Nevertheless, a common understanding emerged. Aging can best be described as a biological process, or more precisely, as a variety of processes that gradually impair the function of tissues, organs and body systems.

Over time, this increases susceptibility to disease and ultimately to death. While chronological age is measured in years, biological age reflects health decline. This view is supported by studies showing that lifespan can be extended by individual gene mutations or medications in model organisms such as mice, suggesting that aging is not immutable.

What ageing means and why it is considered modifiable

Although there is still no universal scientific definition of ageing, experts agree that it is a progressive biological deterioration. This affects tissues, organs and bodily systems over time, thereby increasing susceptibility to disease and death.

While your chronological age only indicates the number of years you have lived, your biological age describes your actual state of health.

Various studies on model organisms such as mice show that targeted interventions such as gene mutations or certain medications can extend lifespan. This suggests that ageing processes can be modified. However, a large part of these findings come from preclinical studies. And here, caution is advised: what works in mice does not automatically apply to humans. Although the biological mechanisms are promising, they have not yet provided any clear causalities. In clinical application, there is often still no proof that the observed effects also occur in humans and actually bring health benefits.

→ Find out more: Study-based! For mice or for humans?

‘Hallmarks of Aging’: Orientation or research trap?

Biological age is a complex and abstract concept that indicates how healthy or aged someone really is in physical, mental and biological terms. Consequently, it cannot be accurately measured by just one indicator.

In the context of the Hallmarks of Aging theory, biological age can be understood as the composite result of various molecular and cellular processes. The list, first published in 2013, was expanded to twelve hallmarks in 2023. These 12 hallmarks of aging provide a useful framework for aging research, but it is mainly supported by studies in animals and laboratory-grown cells. They are also not all equally validated, and only a few, such as genomic instability, telomere erosion, and nutrient sensing, show relevance in human studies. Most of the others are still based on preclinical studies, which means that their relevance to actual human aging has not yet been fully confirmed.

The 12 hallmarks of aging provide orientation

Genomic instability: Over time, DNA damage accumulates, impairing repair and cell function. Measurable via DNA damage markers.
Telomere wear: Telomeres shorten with age, limiting the ability of cells to divide and renew themselves. Measured via qPCR or FISH.
Deregulated nutrient sensing: Important signalling pathways such as insulin and mTOR become unbalanced, accelerating the ageing process. Metabolic markers help to track this.
Mitochondrial dysfunction: mitochondria lose efficiency and release reactive oxygen species, increasing stress.
Chronic inflammation (inflamm-aging): low-grade systemic inflammation increases with age, often assessed via CRP and cytokines.
Epigenetic changes: changes in gene regulation without DNA mutation that affect cellular identity. Mapped via methylation profiles.
Loss of proteostasis: cells lose the ability to manage misfolded proteins, leading to aggregation and dysfunction.
Cellular senescence: Damaged cells stop dividing and secrete harmful factors. Identified via p16INK4a or SA-β-Gal.
Depleted stem cells: Fewer active stem cells reduce tissue regeneration. Measured by stem cell count or function.
Altered intercellular communication: Cell signalling goes awry, promoting ageing and systemic inflammation.
Disabled macroautophagy: cells cannot recycle waste, leading to the accumulation of cellular debris. Traced using autophagy markers.
Microbiome disruption: The gut flora becomes unbalanced, affecting metabolism and immune signalling. Profiled using microbiome sequencing.

Many researchers use this framework to better structure the complexity of aging. However, not all experts view this list uncritically. Richard Miller and Steve Austad warn against treating it as a fixed benchmark. They believe it could stifle scientific curiosity, especially if funding were to be allocated only to projects that align with these categories. Instead of asking new questions, they say, researchers might find themselves slavishly following a predetermined structure without questioning its actual validity.

While Matt Kaeberlein recognises the communicative value of the ‘Hallmarks’, he also emphasises that it is not a closed system. The list provides a useful orientation, but no scientific finality. Mechanisms are named, but real causalities are rarely proven.

Are epigenetic clocks scientifically sound?

A popular but controversial tool for determining biological age is the so-called epigenetic clock. It is based on DNA methylation patterns and is supposed to indicate how quickly a body ages biologically, independently of chronological age.

The idea sounds promising, but in practice it has significant weaknesses. Matt Kaeberlein has tested several of these clocks himself and found strong fluctuations. Using the same blood sample, the measured biological age was between 42 and 63 years.

Peter Attia is also highly critical. In his opinion, these measuring instruments are too simplistic. Instead, he recommends focusing on specific health markers such as VO2 max, muscle mass or insulin sensitivity.

All experts agree that epigenetic clocks have their place in the research environment. However, they lack the necessary reliability and clinical validation for individual health assessments or therapeutic decisions. At present, they provide interesting hypotheses but no reliable recommendations.

The role of epigenetic changes

The role of epigenetic changes in the ageing process is currently the subject of much discussion. Some researchers are working on reprogramming techniques that can be used to partially reverse age-related cell changes.

Initial studies on mice have shown promising results. However, experts are calling for caution: so far, there is a lack of clear evidence that the reversal of certain epigenetic markers actually leads to improved function or health.

A similar picture emerges for cellular senescence. These are cells that no longer divide but continue to remain in the body. Richard Miller criticises the lack of clarity in the definition. The term ‘senescent cell’ encompasses very different cell types, which makes research more difficult.

Although preclinical studies show that the targeted removal of certain senescent cells in mice has positive effects, the transfer to humans remains unclear.

Kaeberlein and Austad emphasise that the hype surrounding so-called senolytics is exaggerated. Although the data to date show biological relationships, they do not show any reliable causalities.

Here, too, many of these results come from animal models. They show possible mechanisms but are only partially transferable to humans. There is currently a lack of clear evidence for clinical use.

Stay sceptical on your longevity journey

Modern longevity research is fascinating, but also full of uncertainties. There is still no clear definition of aging and many of the mechanisms discussed come from preclinical studies. These provide interesting insights, but are only partially transferable to humans. They show possible relationships, but no certain causes.

If you are interested in longevity, you would be well advised not to rely on unreliable measuring instruments or promises made by the media. Instead, you would be better off concentrating on what can already be measured, influenced and scientifically proven today.