How do I knock off thirty years from my age?
Faust, the protagonist in Johann Wolfgang von Goethe’s famous play, poses this question to Mephistopheles in the chapter Hexenküche (Witches’ kitchen). Mephistopheles provides some pretty good advice – considering that he is the devil and this fictitious exchange takes place in the dark Middle Ages:
Begib dich gleich hinaus aufs Feld,
Fang an zu hacken und zu graben
Erhalte dich und deinen Sinn
In einem ganz beschränkten Kreise,
Ernähre dich mit ungemischter Speise,
Leb mit dem Vieh als Vieh, und acht es nicht für Raub,
Den Acker, den du erntest, selbst zu düngen;
Here is the paraphrased essence of the devil’s advice: Seek out a life of moderation, stop being lazy, exercise regularly by ploughing the field and avoid unhealthy foods!
How does the great scholar and scientist Faust respond to these commonsense suggestions?
Thanks, but no thanks. Faust does not like manual labor and is quite happy with his current lifestyle, so he instead opts for plan B – a magic youth potion.
Nearly two centuries after Goethe’s Faust was first performed, our quest for reversing the aging process continues. The magic potion which reverses aging continues to be as elusive as ever, but aging research has made substantial progress during the past few decades. One biological definition of aging is the gradual decline in function observed over time. Humans experience this age-related decline at a whole body or organ level such as memory loss or weakening of muscle strength, but aging also takes place in individual cells. Cellular aging or cellular senescence describes a form of “exhaustion” to the point where cells can no longer divide and a disruption of normal cellular activity. A substantial amount of scientific data suggests that the aging of individual cells plays a central role in the general decline of function in our muscle function, blood flow or metabolism which occurs when we grow older. But understanding cellular aging will not only unlock some of the mysteries of “healthy” aging, it may also help us understand and prevent certain age-associated diseases such as heart disease or cancer.
One of the central mechanisms responsible for the aging of cells is the shortening of telomeres. Telomeres are repetitive DNA sequences at the ends of chromosomes which act as protective caps. Every time a cell divides, its chromosomes undergo a doubling process so that the two daughter cells receive equal amounts of DNA. During the DNA replication and the separation of the newly formed chromosomes, small chunks of DNA are trimmed off at the end of the chromosomes. By having protective telomere caps, the shortening process only affects the telomeres and not the essential gene-encoding parts of the chromosome.
When cells in a tissue are damaged then their neighboring cells or reservoirs of regenerative stem cells and progenitor cells have to kick in, divide a replace the damaged cells. Having long telomeres would allow these regenerative neighbors to keep on dividing and restoring the tissue, whereas short-telomere cells would have to give up early on because their protective telomere caps would dwindle. Regenerative cells such as stem cells are frequently called upon to divide and this is why it is a good thing that these regenerative cells tend to contain high levels of an enzyme called telomerase which helps prevent the shortening of the telomeres. Telomerase thus acts as an anti-aging enzyme. The roles of telomeres and telomerase in cellular aging were first uncovered in the 1980s and 1990s by the pioneers Elizabeth Blackburn, Carol Greider and Jack Szostak, who all shared the 2009 Nobel Prize in Physiology or Medicine for “the discovery of how chromosomes are protected by telomeres and the enzyme telomerase“.
At the 64th Lindau Nobel Laureate meeting, Elizabeth Blackburn reviewed the history of how she and her colleagues identified the role of telomeres and telomerase in the cellular aging process, but also presented newer data of how measuring the length of telomeres in a blood sample can predict one’s propensity for longevity and health. It makes intuitive and theoretical sense that having long telomeres would be a good thing but it is nice to have real-world data collected from thousands of humans confirming that this is indeed the case. A prospective studycollected blood samples and measured the mean telomere length of white blood cells in 787 participants and followed them for 10 years to see who would develop cancer. Telomere length was inversely correlated with likelihood of developing cancer and dying from cancer. The individuals in the shortest telomere group were three times more likely to develop cancer than the longest telomere group within the ten year observation period! A similar correlation between long telomeres and less diseasealso exists for cardiovascular disease.