Life

Research on longevity - insights from science on a long and healthy life

Michael Wäger
from Michael Wäger, BSc, MSc
on 01.10.2024
Longevity research

Who doesn’t want to stay young even though they get old? Longevity research seeks to realise this dream by exploring both science and the art of healthy ageing. In this knowledge blog, you will learn about the 12 key processes of ageing and how to stop the ageing screw from turning.

Human ageing

Human ageing is a multi-level and complex process. Science has been striving for decades to decode this process even more precisely and – if possible – to influence it. This relentless research effort has revealed the “12 signs of ageing”. There are numerous possibilities for putting this theoretical gain from longevity research into practice. Preventing these signs if ageing makes an important contribution to a long and healthy life.

The 12 key processes of ageing – and potential countermeasures

Ageing is influenced by a complex network of biological changes – the 12 key processes of ageing.

  1. Shortening of telomeres
  2. Loss of proteostasis
  3. Genomic instability
  4. Epigenetic changes
  5. Chronic inflammation
  6. Impaired intercellular communication
  7. Mitochondrial dysfunction
  8. Deregulated nutrient sensitivity
  9. Stem cell exhaustion
  10. Inhibition of macroautophagy
  11. Dysbiosis
  12. Cellular senescence

But what specifically do these 12 key ageing processes imply? An in-depth look:

1. Shortening of telomeres 

As we age, the ends of chromosomes, called telomeres, become shorter and can no longer protect the DNA. This can increase the likelihood of genomic instability and impair cell function.

Scientific news: According to basic studies, certain substances, such as fisetin or resveratrol, seem to stimulate the activity of the enzyme telomerase, which can lengthen the telomeres once again. It has also been possible to show telomerase-resilient effects for spermidine, although it is not yet clear whether it stimulates the telomerase or directly protects the telomeres.

2. Loss of proteostasis

Ideally, the proteins in a cell are always correctly folded and present in a suitable quantity. However, studies show that proteostasis changes with increasing age. The folding of proteins is often faulty with age. This is accompanied by a loss of proteostase function, which contributes to the development of many age-related diseases such as Alzheimer's, Parkinson's and cataracts.

Countermeasures: See point 10.

3. Genomic instability

The genome is the entirety of our genetic material and includes all genetic information in a cell. DNA is the spiral carrier of genetic information. DNA is damaged by mutations caused by environmental factors such as oxidative stress or even less efficient DNA repair mechanisms in old age. This also applies to our stem cells, which are responsible for general tissue renewal and regeneration. Damaged DNA can lead to a faulty cell function that impairs the proper function of tissues and organs.

Countermeasures: To protect our DNA, in addition to a healthy lifestyle, the absorption of various antioxidant substances is also beneficial. A mixture of various plant extracts (e.g. EGCG-rich green tea extract, OPC from grape seed extract, the antioxidant-effective enzyme SOD from melon extract), and the body’s own radical scavenger (e.g. coenzyme Q10) is particularly well suited for this, because these can both support and complement each other with their various modes of action.

4. Epigenetic changes

The epigenome is the molecular machinery that regulates the activity of our genes. So-called methylation deactivates and activates our genes. As we age, this regulatory process gets out of control. As a result, certain useful genes are turned off when they should be turned on, and genes that can cause problems are fatally turned on.

Countermeasures: In order to prevent epigenetic changes, the targeted intake of selected active substances is recommended in addition to avoiding harmful external influences (e.g. environmental toxins, free radicals). Modern longevity research is currently focused on alpha ketoglutarate (AKG), known for its role in cellular energy metabolism and its antioxidant capacity. A human study showed that the epigenetic age decreased by 8 years after taking AKG for several months

5. Chronic inflammation

Chronic inflammations that can be influenced by lifestyle factors occur more frequently as we age. These inflammations promote age-related diseases, including cardiovascular diseases, diabetes and neurodegenerative diseases.

Countermeasures: Regular exercise, sufficient sleep and a healthy diet are simple strategies to prevent chronic inflammation and early ageing. In addition, antioxidant intake reduces oxidative stress associated with inflammation. In addition, botanicals such as quercetin, berberine or betaine have direct anti-inflammatory effects and are therefore ideal for the natural control of chronic inflammation.

6. Impaired intercellular communication

Cells interact, among other things, by transduction, the signal transmission to certain receptors where the signals are converted. Extracellular signals are thus converted into specific cellular reactions. However, with age, this communication is often more difficult and becomes more error-prone.

Countermeasures: See point 10.

7. Mitochondrial dysfunction

Mitochondrial dysfunction plays an important role in age-related research. With increasing age, mitochondrial function disorders can occur, which can lead to inflammatory reactions. The mitochondria themselves are damaged by the inflammation, which can lead to a vicious cycle and contribute to a number of health problems.

Countermeasures: While exercise and a healthy calorie balance are an important factor in mitochondrial health, support with special preparations is also possible. The use of coenzyme Q10, the most important mitochondrial antioxidant, is promising. In addition, NADH, alpha ketoglutarate, ginseng extract and berberine also have mitochondrial-protecting potential.

8. Deregulated nutrient sensitivity

As we age, our cells are less exposed to nutrient signals, which affects a cell’s ability to use and produce energy. This can lead to reduced energy and metabolic disorders.

Countermeasures: See point 10.

9. Stem cell exhaustion

With increasing age, stem cells lose their function or die. Because stem cells are responsible for producing new copies of our cells as needed, a lower number or dysfunctional stem cells lead to our tissues being less well regenerated and preserved.

Countermeasures: See point 12.

10. Inhibition of macroautophagia

So-called macroautophagia inhibition occurs when a body’s cells are unable to perform cellular self-cleansing. This leads to the accumulation of damaged or dysfunctional cell components and is associated with cancer, metabolic and neurological disorders.

Countermeasures: Fasting can stimulate cellular self-cleaning (= autophagia) – but not everyone can or would like to integrate regular fasting into their daily lives. Fortunately, there are special substances that stimulate the autophagia process by activating the sirtuins. Spermidine and resveratrol are the most well-known here. More recent study data suggest that pterostilbene and quercetin are also suitable in this context. Autophagia stimulation also prevents an accumulation of damaged proteins and improves intercellular communication. Several factors of ageing are positively affected. 

11. Dysbiosis

The microbiome is the entirety of all microorganisms – such as bacteria, viruses, etc. – in our body. Today, we know that we live in close symbiosis with our bacteria. They affect whether we are healthy or sick and have a correspondingly strong influence on our immune system. Dysbiosis becomes more common with age – a disorder of the normal microbial community. As a result, the risk of neurodegenerative diseases or cardiovascular diseases increases with increasing age.

Countermeasures: High-dose probiotics and special prebiotics can help to restore healthy intestinal flora in dysbioses. Prolonged unhealthy colonisation can also lead to mucosal damage. In this case, special mucosal preparations containing micronutrients that protect the mucous membranes and plant extracts (e.g. L-glutamine, extracts of green tea, chamomile and grape seeds) can contribute to the restoration of an intact intestinal mucosa.

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12. Cellular senescence

Senescent cells are former healthy cells that can no longer divide due to their advanced age. They secrete substances that damage the healthy surrounding cells. These cells, known as zombie cells, increase exponentially with age and lead to tissue and organ damage.

Scientific news: Longevity research is currently researching special substances (= senolytics) that prevent the development of senescent cells or dissolve any senescent cells that are already in existence. The flavonoids fisetin and quercetin are considered the most researched senolytics, and have shown a life-prolonging effect in animal models. Resveratrol and coenzyme Q10 can also delay the onset of senescence due to their positive effect on cell health. Through the general promotion of tissue health, these substances also contribute to another characteristic of ageing – the exhaustion of our stem cell reserves. 

Conclusion: In addition to a healthy lifestyle with a balanced diet, regular exercise and a restful night’s sleep, taking botanical extracts and special micronutrients is an optimal supplement to promote healthy ageing. These nutritious tools can help counteract the signs of ageing and are therefore considered a natural support in the fight against ageing.

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Further reading: 

Aunan, J. R. et al. 2016. Molecular and biological hallmarks of ageing. Br J Surg. 103(2):e29–e46.

Kassis, A. et al. 2023. Nutritional and lifestyle management of the aging journey: A narrative review. Front Nutr.9:1087505.

Yousefzadeh, M. et al. 2021. DNA damage—how and why we age? eLife. 10:e62852.

Zulfiqar, A. et al. 2020. Anti-Oxidant Nutrients and Nutraceuticals in Aging. In: Nutrients and Nutraceuticals for Active & Healthy Ageing. Hrsg.: Nabavi, S. M. et al. Springer Singapore, Singapore. S. 195–216.

Horvath, S., Raj, K. 2018. DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet. 19(6):371–384.

Asadi Shahmirzadi, A. et al. 2020. Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice. Cell Metab. 32(3):447–456.e6.

Demidenko, O. et al. 2021. Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test. Aging (Albany NY). 13(22):24485–24499.

Yiannakopoulou, E. C. 2015. Targeting DNA Methylation with Green Tea Catechins. Pharmacology. 95(3–4):111–116.

Friso, S., Choi, S.-W. 2002. Gene-Nutrient Interactions and DNA Methylation. J Nutr. 132(8):2382S–2387S.

Shay, J. W. 2016. Role of Telomeres and Telomerase in Aging and Cancer. Cancer Discov. 6(6):584–593.

Mazidi, M. et al. 2018. Serum lipophilic antioxidants levels are associated with leucocyte telomere length among US adults. Lipids Health Dis. 17(1):164.

Kubo, C. et al. 2020. Fisetin Promotes Hair Growth by Augmenting TERT Expression. Front Cell Dev Biol. 8:566617.

Wirth, A. et al. 2021. Novel aspects of age-protection by spermidine supplementation are associated with preserved telomere length. GeroScience. 43(2):673–690.

Bagherniya, M. et al. 2018. The effect of fasting or calorie restriction on autophagy induction: A review of the literature. Ageing Res Rev. 47:183–197.

Eisenberg, T. et al. 2009. Induction of autophagy by spermidine promotes longevity. Nat Cell Biol. 11(11):1305–1314.

Hector, K. L. et al. 2012. The effect of resveratrol on longevity across species: a meta-analysis. Biol Lett. 8(5):790–793.

Hassani, B. et al. 2022. Pharmacological Approaches to Decelerate Aging: A Promising Path. Oxid Med Cell Longev. 2022:4201533.

Son, J. H. et al. 2012. Neuronal autophagy and neurodegenerative diseases. Exp Mol Med. 44(2):89–98.

Muñoz-Espín, D., Serrano, M. 2014. Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Biol. 15(7):482–496.

Romashkan, S. et al. 2021. National Institute on Aging Workshop: Repurposing Drugs or Dietary Supplements for Their Senolytic or Senomorphic Effects: Considerations for Clinical Trials. J Gerontol A Biol Sci Med Sci.76(6):1144–1152.

Riva, A. et al. 2019. Improved Oral Absorption of Quercetin from Quercetin Phytosome®, a New Delivery System Based on Food Grade Lecithin. Eur J Drug Metab Pharmacokinet. 44(2):169–177.

Tang, Y. et al. 2012. Resveratrol reduces vascular cell senescence through attenuation of oxidative stress by SIRT1/NADPH oxidase-dependent mechanisms. J Nutr Biochem. 23(11):1410–1416.

Yan, J. et al. 2006. Reduced coenzyme Q10 supplementation decelerates senescence in SAMP1 mice. Exp Gerontol. 41(2):130–140.

Kang, C. 2019. Senolytics and Senostatics: A Two-Pronged Approach to Target Cellular Senescence for Delaying Aging and Age-Related Diseases. Mol Cells. 42(12):821–827.

Guo, C. et al. 2013. Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regen Res. 8(21):2003–2014.

Alf, D. et al. 2013. Ubiquinol supplementation enhances peak power production in trained athletes: a double-blind, placebo controlled study. J Int Soc Sports Nutr. 10(1):24.

Nicolson, G. L. 2014. Mitochondrial Dysfunction and Chronic Disease: Treatment With Natural Supplements. Integr Med (Encinitas). 13(4):35–43.

Shin, E. J. et al. 2020. Red Ginseng Improves Exercise Endurance by Promoting Mitochondrial Biogenesis and Myoblast Differentiation. Molecules. 25(4):865.

Fang, X. et al. 2022. Research progress on the pharmacological effects of berberine targeting mitochondria. Front Endocrinol (Lausanne). 13:982145.

Petrangolini, G. et al. 2021. Development of an Innovative Berberine Food-Grade Formulation with an Ameliorated Absorption: In Vitro Evidence Confirmed by Healthy Human Volunteers Pharmacokinetic Study. Evid Based Complement Alternat Med. 2021:7563889.

Asbaghi, O. et al. 2020. Effects of chromium supplementation on glycemic control in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Pharmacol Res. 161:105098.

Kim, S. K. et al. 2020. Hypoglycemic efficacy and safety of Momordica charantia (bitter melon) in patients with type 2 diabetes mellitus. Complement Ther Med. 52:102524.

Pahwa, R. et al. 2024. Chronic Inflammation. In: StatPearls Publishing, Treasure Island (FL).

Nani, A. et al. 2021. Antioxidant and Anti-Inflammatory Potential of Polyphenols Contained in Mediterranean Diet in Obesity: Molecular Mechanisms. Molecules. 26(4):985.

Lesjak, M. et al. 2018. Antioxidant and anti-inflammatory activities of quercetin and its derivatives. J Funct Foods. 40:68–75.

Li, Z. et al. 2014. Antioxidant and Anti-Inflammatory Activities of Berberine in the Treatment of Diabetes Mellitus. Evid Based Complement Alternat Med. 2014:289264.

Zhao, G. et al. 2018. Betaine in Inflammation: Mechanistic Aspects and Applications. Front Immunol. 9:1070.

Ratan, Z. A. et al. 2021. Adaptogenic effects of Panax ginseng on modulation of immune functions. J Ginseng Res. 45(1):32–40.

Campos, L. D. et al. 2023. Collagen supplementation in skin and orthopedic diseases: A review of the literature. Heliyon. 9(4):e14961.

Gao, Y.-R. et al. 2023. Oral administration of hyaluronic acid to improve skin conditions via a randomized double‐blind clinical test. Skin Res Technol. 29(11):e13531.

Veronese, N. et al. 2020. Glucosamine sulphate: an umbrella review of health outcomes. Ther Adv Musculoskelet Dis. 12:1759720X20975927.

Pontifex, M. G. et al. 2022. Saffron extract (Safr’InsideTM) improves anxiety related behaviour in a mouse model of low-grade inflammation through the modulation of the microbiota and gut derived metabolites. Food Funct. 13(23):12219–12233.

Xiong, J. et al. 2023. Evaluation of saffron extract bioactivities relevant to skin resilience. J Herb Med. 37:100629.

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