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One of the first scientists to seriously study aging was the pioneering immunologist Elie Metchnikoff, who coined the term “gerontology” for the study of aging.[1] Metchnikoff won the 1908 Nobel Prize in Medicine for his work on the functioning of the immune system, which he also applied to his research on aging. He theorized that toxic bacteria in the gut contributed to aging and drank sour milk every day to combat them. Today, we know that the matter is far more complicated than that, but gut bacteria, our gut microbiome, do play a role.[2] 

Not long after Metchnikoff’s Nobel Prize, US biochemist Clive McCay was studying nutrition. McCay fed rats on different diets to investigate how they affected their growth and development. By chance, he discovered that his rats would live longer if he fed them less.[3] This counterintuitive finding, dubbed “calorie restriction”, became the first proven anti-aging intervention in mammals. It also proved efficient in yeast, worms, flies, and other rodents.[4] McCay had discovered the interconnectedness of energy, development, and aging. 

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At this point, it was still believed that while the organism as a whole might age, cells were immortal. In 1961, this view was challenged when US anatomist Leonard Hayflick[5] discovered that human cells in culture are not immortal. They will only divide between 40 and 60 times and then stop. After this, they enter a phase of senescence. This phenomenon is now known as the Hayflick Limit. 

Initially, it was not clear why cells would not be able to divide indefinitely. In the 1970s, Russian biologist Alexei Olovnikov found a clue. He recognized that cells could not completely replicate the ends of their chromosomes.[6] 

With each division, the chromosomal ends lost a little DNA, growing slowly shorter over time. Finally, Australian biologist Elizabeth Blackburn got to the bottom of the matter. With her colleagues Carol Greider and Jack Szostak, she discovered and described the nature of structures called telomeres – a discovery for which they shared the 2009 Nobel Prize in Medicine.[7] Briefly explained, telomeres are repeating sequences of DNA located at the ends of all our chromosomes. The sequences do not code for any necessary information but are there to protect the rest of the DNA. Think of them as the aglet on the end of a shoelace that prevents the lace from dissolving. When the protective telomeres become too short, the cell will arrest its activity to avoid excessive DNA damage, which could make it turn cancerous.[8] 

Some cells, however, have a way of working around this problem. These cells can continuously add more telomere using an enzyme called telomerase. This helps them maintain their telomere length and makes them immortal – at least in theory. Stem cells are the primary users of this mechanism in our bodies.[9] Different kinds of stem cells are distributed in various tissues and tasked with dividing and then differentiating into new cells. For this reason, it makes sense for them to have access to telomerase.  

If a lack of telomeres makes cells mortal, and if telomerase can reverse this, that would seem to imply a quick fix for aging by simply triggering this mechanism in normal cells. It turns out that the matter is not that simple, but more about that later. 

Finally, in the 2000s, British biologist Aubrey de Grey founded Strategies for Engineered Negligible Senescence (SENS), an organization that advocates for life extension, studies aging, and provides funds for anti-aging research. Together with major advances in many subfields of aging research, this has laid the foundation for the surging popularity of anti-aging science.  

It is impossible to give a fair summary of the history of anti-aging research. In the last few decades especially, thousands of people have made meaningful contributions. New scientists are flooding into the field, but so are new entrepreneurs, donors, volunteers, and hobbyists.  

Generally speaking, there are two major challenges involved when we consider the aging process as a disease to be counterbalanced with pharmaceutical drugs (or regenerative medical procedures). First of all, if such drugs are to be taken preventively, they would need to be completely free from side-effects. While adverse side-effects might be considered tolerable in the treatment of severe diseases, they would not be accepted in cases of aging or lifestyle indications.[10]

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Secondly, demonstrating the scientific efficacy of anti-aging requires long-term clinical studies that would be both laborious and expensive. The effects of aging on the body take place very slowly (subchronically), making it highly challenging to design scientifically and statistically sound and meaningful clinical studies and to finish them within a timeframe that is manageable and affordable for companies. Because the expected effects are small and slow to evolve, studies need to be large in scale and measure outcomes over many years. This, more than issues surrounding patenting, seems to be a main reason why large pharmaceutical corporations are wary of anti-aging and lifestyle drugs, preferring to focus on more severe and immediate indications, such as diabetic kidney disease. Closely linked to the research effort is the question of whether health insurances would cover preventive anti-aging treatments.

Anti-aging research now encompasses many wildly different ideas and approaches. We can get an overview in a 2013 paper entitled “The Hallmarks of Aging”.[11];The model presented in this paper is inspired by a similar model for cancer called “The Hallmarks of Cancer”. It describes the different biological alterations thought to play a role in aging. If one of the hallmarks is artificially aggravated in a model organism, aging will accelerate. If it is ameliorated, the organism will live longer. In other words, these hallmarks show us which problems we need to solve.

References

[1] Martin, D.J. and L. Gillen 2014. Revisiting Gerontology’s Scrapbook: From Metchnikoff to theSpectrum Model of Aging. The Gerontologist 54 (1):51-8.


[2] Nagpal, R. et al. 2018. Gut microbiome and aging: Physiological and mechanistic insights.Nutrition and Healthy Aging 4(4):267-85.


[3] McCay, C.M. and M.F. Crowell 1934. Prolonging the Life Span. The Scientific Monthly39(5):405-14.


[4] Taormina, G. and M.G. Mirisola 2014. Calorie restriction in mammals and simple modelorganisms. BioMed Research International. Special issue: Aging and Longevity between GeneticBackground and Lifestyle Intervention (2014).


[5] Hayflick, L. and P.S. Moorhead 1961. The serial cultivation of human diploid cell strains.Experimental Cell Research 25(3):585-621.

[6] The chromosomes are the structures that contain our DNA. Each of us have 46, 23 from eachof our parents.


[7] https://www.nobelprize.org/prizes/medicine/2009/summary/.

[8] Campisi, J. 2000. Cancer, aging and cellular senescence. In Vivo 14(1):183-8.


[9] Cong, Y. et al. 2002. Human telomerase and its regulation. Microbiology and MolecularBiology Reviews 66(3): 407-25.


[10] For an investigation of negative side-effects on post-marketing withdrawals of lifestyle drugsin the pharmaceutical industry, see Onakpoya, I.J. et al. 2016. Post-marketing withdrawal of anti-obesity medicinal products because of adverse drug reactions: a systematic review. BMCMedicine 14:191.


[11] López-Otín, C. et al. 2013. The hallmarks of aging. Cell 153(6): 1194-217.