By Yechezkal Freundlich, Senior Science and Technology Editor
“Nothing is certain but death and taxes” is a phrase coined by Benjamin Franklin in a letter to Jean-Baptiste Le Roy in 1789. This idiom has held true, until now. Life and the battle against death is something humanity has been fighting for millennia. Religions have been built on eternal life and conquering death. People have fantasized about the perplexities and wonders of immortality as far back as the Epic of Gilgamesh, around 4,000 years ago. Cosmetic companies have made billions of dollars selling de-aging products, banking on the dreams of people who will gladly spend a fortune just to postpone aging — of their appearances, not their bodies — by a year or two. Now, the future is here, and biological and physiological “youth potions” will soon be a reality.
There are many biological indicators of aging. As people get older, their DNA and chromosomes become damaged, telomere sequences shorten, proteins misfold and aggregate and cell lysis becomes more prevalent. One key debate in scientific literature is how large a role stem cells play in aging. Whether this is considered the main element or simply a symptom, once stem cell production and mitosis begins to decline, the body ages. Stem cells, located in tissue throughout the body, are in charge of repairing and/or replacing dying cells: they divide into daughter cells from replication, producing new stem cells, specific-based progenitors or both. Essentially, stem cells play a crucial role in regulating cell reproduction and in the aging process.
What if stem cells could be used to replace dying tissue as a form of reverse aging? A group of scientists in Beijing, in a 44-week study, discovered a method for de-aging monkeys. The researchers infused cynomolgus monkeys with senescence-resistant mesenchymal progenitor cells, or SRCs, which provided longevity for the FOXO3 gene, reducing markers for chronic inflammation, cellular degradation and tissue decay. Over time, cells accumulate DNA damage and slow down or stop dividing, a process called cellular senescence. These engineered senescence resistant cells delay or avoid DNA damage so they can repair tissues longer.
Injecting stem cells into people to increase the cell volume to prevent tissue decay may sound simple, but there are many issues that have prevented researchers from doing this experimentation until now. Injected stem cells would have to come from the subject, as otherwise they would be treated as foreign and killed by the body’s defense system. The injected cells would have to arrive at the desired tissue in order to have the desired effect, and they would need to proliferate at a certain time and only to a specific amount. If the replication of the cells were to become unregulated, the large clumps of cells might become cancerous.
The scientists engineered these SRCs for elderly macaques, as they exhibit similar physiology to older humans. The monkeys received biweekly intravenous injections of 2,000,000 cells per kilogram of weight. The study found that the monkeys exhibited signs of de-aging while maintaining stellar health, with no adverse side effects appearing. The stem cells triggered rejuvenation for test subjects, increasing cognitive and motor function and reducing age-related issues such as muscular atrophy, osteoporosis and fibrosis.
The SRCs helped reduce aging in ten different physiological systems and over 61 different tissues. The transcriptomic and DNA methylation clocks, which estimate biological age, showed a reduction of the biological age of systems like the lungs, skin, muscles and hippocampus, as well indicated improved reproductive capabilities. The team found an increase in sperm count in the macaques and no tumor development. The macaques had an increase in genomic capabilities, stronger immune systems and improved reactions to oxidative stress.
Upon further analysis, the researchers found that the SRCs produced exosomes (membrane-bound extracellular vesicles used for communication and macromolecular transport). These exosomes were enriched in “geroprotective” proteins and metabolites, and appeared to mediate anti-aging signaling. These findings, coupled with the lack of tumor formation or an immune response to the SRCs, indicates a successful experiment.
This is not the start of producing capable “youth potions.” It is, however, the beginning of discussing producing “youth potions.” The experiment — whilst impressively long for a highly-functioning organism study — is too short in regard to the macaque lifespan, taking up only a 23rd of their life, to evidently prove success. Latent carcinogenic symptoms may still appear. Furthermore, while the SRCs definitely improved a wide variety of the organisms’ physiology, aging is multifactorial, so stem cells cannot halt it altogether. They can, as this study found, potentially slow it down for specific tissues and systems. Exosomes need further study in order to determine their function, and the biggest hurdle to overcome — safely transitioning from monkeys to humans — will further postpone the arrival of any anti-aging drugs on the market.
While it may be some time before humans can significantly slow molecular aging, this experiment has vastly accelerated the “immortality fantasy.” The Beijing scientists behind this experiment have brought this idea to the forefront, potentially bringing humanity one step closer to overcoming the greatest certainty to ever exist, the certainty of death.
Photo Credit: Unsplash