From the early records of history, humans have always been in search of the elixir of life, the source of immortality, or the philosopher's stone; we have long been fascinated with stories about vampires, beings that live forever, looking young forever. In just few years, however, scientists are turning what once was a fantasy to a reality. Looking (or even living) young forever might be a possibility thanks to researchers getting excitingly closer to crack the ageing code.
In 2022, various investors from the bay area in the United States, including Jeff Bezos himself, betted for rejuvenation and longevity investing an unprecedented amount of around $300 million dollars to crack the ageing code. The foundation of this company, Altos Labs, brought a lot of attention from investors around the world into the area of rejuvenation. Altos Labs recruited some of the most capable scientists in ageing from the world and placed them in the same room, with the vision of tackling ageing and delaying death as much as possible.
Anti-ageing technology: some developments and drawbacks
Ageing is the accumulative result of epigenetic dysregulation (how DNA is organised), coupled with genetic mutations that take place over time. Interestingly, the key to crack this code relies on babies not ‘inheriting’ the parents' age at conception, but resetting it. Many current techniques rely on this resetting, which scientists refer to as reprogramming. By using just four different proteins–the Yamanaka factors (see Box 1)–scientists manage to reverse the age of a 50-year-old human skin cell to an embryonic state of age zero. Current attempts are focusing on fine-tuning that age reversion while avoiding all sorts of biological peril.
Box 1.The Yamanaka Factors, explainedThe Yamanaka factors, which include Oct3/4, Sox2, Klf4, c-Myc, are a set of protein transcription factors that help the creation of pluripotent stem cells (i.e., cells that carry potential to develop into any cell in the body).
Another company in the United States called TurnBio is using the Yamanaka factors as messenger RNA to target several tissues with a huge progress on skin rejuvenation. This company is close to being the first to truly rejuvenate human skin tissues on an epigenetic level.
»By using just four different proteins—the Yamanaka factors—scientists managed to reverse the age of a 50-year-old human skin cell to an embryonic state of zero. Current attempts are focusing on fine-tuning that age reversion while avoiding all sorts of biological peril.«
However, not everything is bliss with manipulating the Yamanaka factors. Partial reprogramming of a transgenic mouse expressing the Yamanaka factors under an inducible drug (doxycycline), showed development of teratomas in epithelial and gastrointestinal tissues. This is due to how one of the four factors is an oncogene, which promotes cellular differentiation (c-Myc). In short, the process may cause cancerous cells to develop, which is why we might see some delays with rejuvenation products designed on the basis of these factors.
As an alternative and to my knowledge, other companies such as Calico and Shift Biosciences are developing substitutes of Yamanaka factors which might eliminate the risk of developing cancer. These companies could have an easier pathway to develop therapeutical applications if they manage to prove that their rejuvenation factors are safe.
»While the technological developments in anti-ageing are getting increasingly successful at unprecedented rates, many scientists—myself included—often take a step back to think over some deeper questions. What would the issue be with ageing if we left it to be, and crucially, is it truly meaningful to beat aging? «
How much rejuvenation could we get? How safe is it, and how much would it cost?
These are typically the questions I hear from people in the field and not surprisingly, the answers vary depending on who you ask. On average and in colloquial terms, the extent of rejuvenation could be interpreted as ‘how many years can I get off my back’. Recent publications have shown that rejuvenation of human fibroblasts achieved a reversion of 30 to 40 years of epigenetic age. This might be a reality soon on the market and the prices would likely be sky-high. However, the delivery method and the tissue/organ chosen for rejuvenation might have quite different effects.
People show true excitement with the possibility of skin rejuvenation, and many of the recent publications have focused on this issue, but researchers argue that there is a big difference between looking young and feeling young. Of course, this might be interpreted quite subjectively, but precedents of blood rejuvenation in mice have shown that the presence of young blood in an aged mouse has several positive impacts during parabiosis experiments.
Rejuvenation beyond the glossiness of your skin: Lifespan extension and a decrease in disease
Beyond its aesthetics aspects, rejuvenation can, as the word suggests, quite literally make your body young again. Paul Bert and collaborators in the mid-1800s tried parabiosis for the first time. It consisted of the stitching together of blood vessels of a young mouse with those of an aged mouse. The free circulation of young blood in the old mouse caused a significant decrease in inflammation and organ failure; immunity was also restored. Recent advances have shown that young blood in an aged mice also decreases the chances to develop Alzheimer's and other neurological diseases. To add icing on the cake, Bert and others reported that the young blood in the aged mouse also led to an increase in lifespan of approximately 30%.
Depending on the tissue targeted for rejuvenation, humans can improve considerably their healthspan and even their lifespan, and this is what has kept investors interested in this field. Researchers in the area have done deep progress on the rejuvenation of skin, heart, and blood, which will probably be the first therapies to be used in humans.
Slowing down during the race to be forever young: questions that matter
While the technological developments in anti-ageing are getting increasingly successful at unprecedented rates, many scientists—myself included—often take a step back to think over some deeper questions. What would the issue be with ageing if we left it to be, and crucially, is it truly meaningful to beat aging? These are just a couple among the many that surface to my mind at times after turning off the lights at the lab.
Knowing all that you know now, would you still get a rejuvenation treatment if you had the chance? Would you rather look younger or live longer? In a world where everyone were to live with repeated rejuvenation treatments, what impact would we expect on an already complicated society and economic system?