FOREVER YOUNG
Alzheimer Dementia (AD), Parkinson, many forms of cancer and cardiovascular diseases are primarily age related; the older we grow, the greater the probability that we will be afflicted by one of these diseases. Even though science has discovered many novel approaches to deal with cancer and have successfully extended the lives of many cancer patients, progress in finding a cure for AD or Parkinson and many forms of cancer has been limited.
Scientists have, however, been working on finding ways and means to slow down, or even halt or reverse the ageing process, thereby not only extending life but keeping the diseases attributed to the ageing process at bay and making these additional years of life disease free and therefore enjoyable. If the ageing process could be delayed or even reversed, the age-related diseases would not strike the elderly.
In a fascinating and very readable book entitled “The Melatonin Miracle, Nature's Age-Reversing, Disease-Fighting, Sex-Enhancing Hormone”, authors Walter Pierpaoli and William Regelson proposed that Melatonin can do precisely that: slow down senescence, extend life and keep people healthy even in old age. The two doctors based their statements on extensive experiments on mice and rats and even claim in their book that by administering melatonin, they could reverse the early onset of Parkinson’s disease in a patient. They further attribute to melatonin the role of the conductor of an orchestra that coordinates the functioning of all other hormones in our bodies.
Melatonin is a hormone produced and released primarily by the Pineal Gland. The production is connected to time of day, increasing when it is dark and decreasing when it is light. It helps with the timing of our circadian rhythm (24-hour internal clock) and is administered to individuals suffering from sleep disorders or jet lag. It has shown positive results in clinical trials on patients with cancer and is used in chemotherapy for cancer patients; as a powerful antioxidant, the hormone appears to protect the mitochondria of the cells that could be affected during chemotherapy. Many doctors prescribe melatonin to patients afflicted by Parkinson’s disease.
Melatonin production decreases with age and Pierpaoli and Regelson suggest that it is this decrease that is responsible for senescence and the onset of age-related diseases. The authors were, however, clearly carried away by their enthusiasm because even though many of the benefits of melatonin are undisputed and its role is greater that only regulating the circadian clock, an overarching role in regulating all the hormones in our body is improbable. Besides, the authors have not taken the role of genetics and gene mutations in the ageing process into consideration. Which brings us to the next topic.
It is already well established that many diseases such as cancer and Alzheimer’s are the result of undesired genetic mutations. The probability of these mutations grows exponentially as we grow older bringing with them the dreaded age-related diseases mentioned above.
In a landmark study published in April 2022 by scientists of the UK Dementia Research Institute at Cardiff University in Nature Genetics, 42 previously unknown AD-related genes have been discovered, adding to the 33 which were already known. Through these 75 genes associated with AD, the scientists have found new pathways that lead to Alzheimer, one of them associated interestingly with inflammation that is in turn associated with many other diseases. One protein associated with AD that the authors singled out is tumour necrosis factor alpha or TNF that is also involved in many autoimmune diseases such as rheumatoid and psoriatic arthritis, Crohn’s disease and type 1 diabetes. The study seems to suggest, therefore, that neurodegenerative diseases may all have a common cause even though it is well known that there are different pathways that lead to Alzheimer’s because the disease “presents differently and progresses differently in different people” as Dr. Richard Isaacson, director of the Alzheimer’s Prevention Clinic in the Center of Brain Health at Florida Atlantic University’s Schmidt College of Medicine puts it. According to the authors, 60-80% of Alzheimer disease risk is based on our genetics, the remaining 20-40% risks can be attributed to lifestyle habits such as smoking, lack of exercise or a poor diet. The question arises as to what exactly causes one or more of the 75 identified genes to mutate in such a way that they trigger Alzheimer’s, Parkinson or other neurodegenerative diseases attributed to ageing.
The answer to that question is: Epigenetics. On 27 October 2021, I posted on this blog an article on EPIGENETICS and it would provide a better understanding of what follows next. Epigenomes are chemical compounds that modify, or mark, the genome in a way that tells it what to do, where to do it, and when to do it. Different cells have different epigenetic marks. In other words, epigenomes turn a gene on or off like a switch.
In the year 2020, Professor Vittorio Sebastiano and his team from the Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA published a breakthrough discovery that could reverse the ageing process by introducing mRNA with instructions to repair mutated epigenomes and thus reverse the undesirable changes that had been caused to the cells. The authors introduce their paper as follows:
“Aging is characterized by a gradual loss of function occurring at the molecular, cellular, tissue and organismal levels. At the chromatin level, aging associates with progressive accumulation of epigenetic errors that eventually lead to aberrant gene regulation, stem cell exhaustion, senescence, and deregulated cell/tissue homeostasis. Nuclear reprogramming to pluripotency can revert both the age and the identity of any cell to that of an embryonic cell. Recent evidence shows that transient reprogramming can ameliorate age-associated hallmarks and extend lifespan in progeroid mice. However, it is unknown how this form of rejuvenation would apply to naturally aged human cells. Here we show that transient expression of nuclear reprogramming factors, mediated by expression of mRNAs, promotes a rapid and broad amelioration of cellular aging, including resetting of epigenetic clock, reduction of the inflammatory profile in chondrocytes, and restoration of youthful regenerative response to aged, human muscle stem cells, in each case without abolishing cellular identity.”
Sebastiano’s process using mRNA functions not only at the level of the cell but also at that of tissue.
A spin-off of Stanford University, Turn Biotechnoligies or turn.bio, located in Mountain View, Silicon Valley where professor Vittorio Sebastiano is co-founder and Scientific Advisory Board Chairman is pursuing research in this exciting area. The company describes its brief as follows:
“Turn Biotechnologies develops mRNA medicines that induce the body to heal itself by instructing specific cells to fight disease or repair damaged tissue. We are focused on reprogramming the epigenome – a network of chemical compounds and proteins that control cell functions by influencing which genes are active – to restore capabilities that are often lost with age.”
The start-up has already succeeded in repairing and rejuvenating human skin, muscle and blood cells in the laboratory. Clinical studies with volunteers are expected to initiate within the next two years. The interest is so great that the company has had to place people on waiting lists.
There are, however, justified concerns regarding this therapeutic approach. A study conducted on mice in 2013 showed that if this therapy is prolonged for too long or is too intensive, it can lead to cancer. This is not surprising since cancer is an uncontrolled multiplication of cells that invades the whole body and turning on a gene without it being subsequently turned off will make cell multiplication uncontrollable. The challenge for turn.bio is thus to ensure that this does not occur by finding the correct dosage.
The start-up is working at the present time on a more modest project: skin therapy that would rejuvenate the skin, accelerate healing of wounds in the elderly and restore the original colour of grey hair. The choice of skin as the first organ on which to focus epigenetic clinical trials is deliberate because it can be easily minutely observed and scrutinised unlike internal organs such as a liver or a heart.
Yet another approach that is being tried out is blood plasma therapy. Alkahest, another Stanford spin-off, has been administering blood plasma infusions of young and healthy donors to patients inflicted with Alzheimer’s disease and the results are promising.
The rejuvenation of human cells and tissues will not make humans eternal but it could extend life to 120 or 150 years and above all, make these additional years free of dreaded diseases such as Alzheimer’s, Parkinson, cancer or other neurodegenerative diseases and therefore make the additional years worth living.
Sources:
- Walter Pierpaoli & William Regelson, The Melatonin Miracle, Pocket Books 1996, ISBN 978-1-4516-1312-4
- https://www.nature.com/articles/s41588-022-01024-z
- https://www.nature.com/articles/s41467-020-15174-3
- https://doi.org/10.1038/s41467-020-15174-3
- https://www.turn.bio/about
- Gioa da Silva, Neue Zürcher Zeitung, “Im Silikon Valley arbeiten Forschende daran, das Altern rückgängig zu machen.Bei Mäusen funktioniert das schon. Nun werden Studien mit Menschen durchgeführt”. NZZ, 02.04.2022, https://www.nzz.ch/wissenschaft/im-silicon-valley-arbeiten-forschende-daran-das-altern-rueckgaengig-zu-machen-bei-maeusen-funktioniert-das-schon-nun-werden-studien-mit-menschen-durchgefuehrt-ld.1665387?mktcid=smsh&mktcval=E-mail
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