Anti-Aging: Promising Developments

When it comes to the question of how to increase life expectancy while remaining fit and healthy, lifestyle modification is always mentioned first. At first glance, implementation seems easy: a healthy diet, plenty of exercise, sufficient sleep, and mental and physical relaxation. On closer inspection, however, some people respond with a hesitant “but”.

There are life situations that make rapid lifestyle changes difficult: What can you do if every step causes pain? What does a healthy diet look like if you have food allergies? Is it even possible to avoid stress when you are going through a difficult period in life, for example after a painful loss or while living with an anxiety disorder? The lifestyle route is multifaceted and long. In such cases, some kind of booster in the form of a cocktail of active ingredients might not sound like a bad idea.

Anti-ageing through food supplements?

Anyone considering taking food supplements for this reason will quickly find themselves in an impenetrable jungle of information. The drawer of advertised anti-ageing products is overflowing. But what is true, and how can we recognise half-truths or even empty promises? Taking such preparations can sometimes also be dangerous, says specialist pharmacist Martin Smollich, among others. In the age of the internet and globalisation, it is possible to buy almost anything – including products that are not even approved in Germany.

The only sensible approach is a clear appeal to reason: examine products carefully and look for scientifically credible studies that demonstrate effectiveness and safety. Alternatively, seek advice from a competent source. This protects your health and saves you money.

We have compiled the latest developments in anti-ageing for you.

The anti-ageing research pipeline

It is no longer only universities, hospitals and research institutes that are dedicated to anti-ageing. Increasingly, young start-ups are also entering the field. Encouragingly, some of them intend to follow the demanding, multi-stage approval process that applies to medicines. We regard this as an important step towards moving beyond the confusing grey area of supplements. Funded by influential investors, these companies offer hope for further serious research and development based on the existing body of fundamental knowledge. Several strategies are being pursued, targeting different known causes of biological ageing.

Intervention strategies in anti-ageing research

The most promising treatments currently being investigated to alleviate or even reverse the consequences of ageing involve influencing regulatory mechanisms related to autophagy, cellular protection (apoptosis/senescence), protein biosynthesis and gene activity. This is achieved by inhibiting or stimulating regulatory pathways with endogenous substances produced by the body or with exogenous active ingredients. Positive results have been demonstrated for some of these intervention strategies in preclinical studies and are currently being evaluated in clinical trials.

Intervention strategy 1: Influencing the body’s own autophagy recycling system

One of our central quality-control systems for cellular function is autophagy. In this process, molecules that are no longer needed, harmful or incorrectly assembled are broken down and recycled. However, the capacity for autophagy decreases with age. Stimulating autophagy is believed to have a positive effect on lifespan.

The positive effects of calorie restriction have been studied extensively. The various forms of fasting are discussed controversially in this context. The fasting-mimicking diet and the Longevity Diet, developed by Professor Dr Valter Longo and already tested in several clinical studies, have produced promising results. His fasting-mimicking nutrition programme with complete meals is called ProLon and is also successful because it avoids the unpleasant sensation of hunger.

Several years ago, the molecule spermidine was also identified and studied as an endogenous polyamine involved in autophagy. More recently, it was investigated at Charité Berlin in connection with combating SARS-CoV-2, because the virus blocks autophagy in infected cells. Regarding its effect as an anti-ageing compound, initial clinical study results suggest that taking spermidine may have positive effects.

You can learn more about this compound in our article Spermidine: insights into one of the most important polyamines.

Intervention strategy 2: Influencing cellular protection

When cells are at risk of becoming abnormal, a natural mechanism is activated that kills and removes the cell through apoptosis. Another tissue-protection programme is programmed cell-cycle arrest, known as senescence. Affected cells do not die but remain in an almost inactive state. Among other things, they release pro-inflammatory substances, which can sometimes have beneficial effects, such as in wound healing, but are generally considered to promote inflammation and therefore negatively affect health, a process known as “inflammaging”. Senescence also plays a role in the inflammatory processes associated with COVID-19, as the research team led by Prof. Christian Drosten at Charité Berlin was able to demonstrate. If senescent cells accumulate over the course of life, this can promote diseases such as atherosclerosis, diabetes and cancer – conditions associated with ageing.

Active ingredients designed to selectively remove senescent cells are known as senolytics. They are currently being tested in humans in relation to ageing and a wide range of diseases. Examples of such compounds include navitoclax, fisetin, quercetin and dasatinib. Researchers are testing not only established medicines and secondary plant compounds, but also newly discovered chemical substances believed to have senolytic effects.

Intervention strategy 3: Influencing protein biosynthesis

Research into protein biosynthesis focuses particularly on mitochondria – cellular organelles with their own DNA that nevertheless interact with the DNA in the cell nucleus. Approximately 1,700 mitochondrial genes have been identified to date, 300 of which are associated with mitochondrial diseases. Mitochondria are also referred to as the “powerhouses of the cells” because they provide energy for all processes in the body. They influence metabolism and the immune system and control the cell cycle. Peptides, smaller protein molecules encoded by mitochondrial genes, are among the substances involved. A malfunction or impairment of gene expression has serious consequences because the body’s own peptides are assembled incorrectly or only in reduced quantities. Mitochondrial diseases are not typical conditions observed only in old age; they can occur at a young age and may then cause accelerated biological ageing.

You can read more about the relationship between mitochondria and cellular ageing in our article When cellular structures become diseased: mitochondrial disease. You can determine your own biological age with the bioAge Test from neotes.

One research approach is the development of peptide analogues for therapeutic use that are capable of interacting with receptors on the cell surface and restoring protein homeostasis. Peptides are generally considered to have great potential. They are already used for numerous diseases, are relatively easy to reproduce and are the subject of extensive research. A large peptide database is currently being developed by the company CohBar. It is also investigating the use of various peptides in mitochondrial and age-related diseases.

Another research approach aimed at preventing defective protein biosynthesis is gene therapy. Scientists at the Max Planck Institute for Biology of Ageing in Cologne have demonstrated in cell cultures that a modified virus can break down mutated mitochondrial DNA using a so-called gene-editing tool. Following successful testing in animal models, the necessary procedural steps are currently being reviewed and the safety of use in patients is being assessed.

Intervention strategy 4: Influencing gene activity

Our organism is controlled by a perfectly coordinated network of regulatory mechanisms. Biochemical molecules produced through genetic coding act as signalling substances that interact with cellular receptors and trigger entire cascades of further actions. The route from the initial signal to the desired response is known as a signalling pathway. Dysregulation contributes to ageing or is an expression of it.

In ageing research, known signalling pathways, signalling molecules and their interactions are being targeted. In many cases, these are already established exogenous active ingredients used in medicines for age-related diseases that are now being investigated to determine whether they may also have an anti-ageing effect. These medicines include dasatinib, developed for the treatment of leukaemia; acarbose and metformin, used to treat type 2 or secondary diabetes; nebivolol and metoprolol, which are beta blockers; and acetylsalicylic acid, used as a blood thinner and painkiller. The most promising medicine is metformin. Its effects at the molecular level are complex, but it provides an example of the enormous potential of such compounds for anti-ageing research and development.

Another strategy is the stimulation or supplementation of endogenous metabolites or vital substances – a satisfactory term for this class of substances has not yet been established – likewise with the aim of influencing the activity of genes or important enzymes. Examples include so-called nicotinamide adenine dinucleotide (NAD) “boosters”, such as nicotinamide riboside or nicotinamide mononucleotide, and calcium alpha-ketoglutarate, which are currently among the best-known compounds believed to have anti-ageing effects. NAD boosters stimulate the function of sirtuins, endogenous enzymes that regulate numerous cellular processes and whose levels decline during ageing. Supplementation with calcium alpha-ketoglutarate also appears promising. Alpha-ketoglutarate is produced in the citric acid cycle, an important metabolic pathway whose intermediate products act as signalling molecules and participate in numerous additional signalling pathways. However, it is not used only in mitochondria; it also acts as a cofactor in many important enzymatic processes. It has been shown that the concentration of calcium alpha-ketoglutarate in peripheral blood decreases with age. Preclinical studies in various organisms have also demonstrated that supplementation with calcium alpha-ketoglutarate has positive effects on lifespan and, in particular, on healthspan, meaning the disease-free period of the overall lifespan.

Good to know: You can read more about this compound in our article Calcium alpha-ketoglutarate (CaAKG).

Will anti-ageing become a reality? A conclusion

There is a great deal in the anti-ageing research pipeline. Detailed knowledge of cellular mechanisms gained through state-of-the-art technologies provides an extremely precise view of new potential intervention points in ageing processes. However, what also becomes clear time and again is the complexity of the relationships involved. Adjusting one mechanism can produce unwanted effects elsewhere. For this reason, clinical studies in humans are indispensable, including when established medicines are being used in an anti-ageing context or when apparently harmless food supplements are involved. Side effects and interactions are serious factors, and even promising intervention strategies can reveal one problem or another. Nevertheless, anti-ageing research can already point to many positive results, bringing us significantly closer to humanity’s dream of ageing healthily. It remains exciting to see what new findings emerge from long-term studies such as the large-scale TAME study involving interdisciplinary research groups, as well as from the research and development activities of the start-ups mentioned above.

At neotes, we are convinced that it is possible to age more slowly and healthily. We continuously monitor the latest developments in anti-ageing research. With us, you have a competent and experienced partner by your side who keeps you informed, provides comprehensive advice and offers only products that have been thoroughly tested.