From rejuvenation using young blood, calorie restriction, stem cells, and iPS cells to hot-topic anti-aging drugs and "senolytics," which target senescent cells—we explain where global longevity research stands today in terms that are easy for everyone to understand.
The words "immortality" and "longevity" have become buzzwords in society, but how far has cutting-edge research actually progressed?
We will explore the mechanisms of aging and the latest research methods in an easy-to-understand way for the general public.
Table of Contents
1. Why do we age? The starting point of research
First, as a basic principle, our bodies are made up of many "cells." When we are young, cells actively divide to maintain the body, but as we get older, "senescent cells" that have lost their function accumulate in the body. Recent research has revealed that these senescent cells are the "main culprits" affecting aging and lifespan. In other words, "reducing senescent cells and increasing young cells" is thought to be the key to immortality and longevity.
2. Rejuvenation with "young blood"?
In 2005, a highly unique study was published in the world-famous scientific journal Nature. It was an experiment called "parabiosis," where the blood vessels of young mice and old mice were connected to circulate blood. As a result, the old mice were rejuvenated, and the young mice aged. This suggests that young blood contains substances that energize cells, while old blood contains waste products that cause cells to age. At the mouse level, it has been demonstrated that rejuvenation is possible through blood exchange alone.
3. Does calorie restriction extend lifespan?
"Eating until eight-tenths full" has long been said to be the secret to longevity, and its effects have also been scientifically debated. In a famous study, monkeys that reduced their calorie intake by 30% were reported to have extended lifespans, but another study (NIA) showed no effect. The difference lies in the "original diet." If someone has been eating a biased diet full of fats and carbohydrates, calorie restriction can lead to dramatic health improvements, but it has been pointed out that if someone is already eating a well-balanced diet like Japanese food, excessive restriction may lower bone density or damage health. Unreasonable dieting should be avoided.
4. The power of stem cells and iPS cells
"Stem cells" are versatile cells that can become any type of cell. "iPS cells," which became famous through Professor Shinya Yamanaka's Nobel Prize, are a technology that artificially creates young and versatile cells from one's own skin cells or other cells. Currently, research in regenerative medicine using this to cure diseases is progressing rapidly. Also, research using specific viruses to directly act on cells in the body and rejuvenate the organs themselves has succeeded in mice, with an amazing result of extending lifespan by about 9%. However, safety hurdles such as the risk of cancer are high, and a careful process is required for application to humans.
Let me explain in a little more detail.
(1) What are stem cells? (The "original" cells of our bodies)
Our bodies are made up of tens of trillions of cells, but not all of them have a fixed role from the beginning. Stem cells possess the following two special abilities.
- Self-replication ability: The ability to copy and increase cells identical to themselves.
- Differentiation ability: The ability to change into all types of cells in the body, such as muscle, nerve, and blood cells.
They are truly the "raw material" for all parts of the body. This ultimate existence is the "pluripotent stem cell" that appears during the process where a fertilized egg divides and grows into a baby. Because it can create everything in the body, it has been researched for years as a dream of medical application.
(2) The emergence of ES cells and the ethical wall
Previously, "ES cells (embryonic stem cells)" having properties close to these pluripotent stem cells were the mainstream of research. However, to make these, it was necessary to use fertilized eggs (which have the potential to become babies in the future), and they had a major bioethical problem. Also, because they were made from other people's cells, the risk of "immune rejection" occurring in the patient's body when transplanted was also an issue.
(3) The birth of the game changer "iPS cells"
The one that solved this ethical wall and rejection problem is the iPS cell (induced pluripotent stem cell) discovered by Professor Shinya Yamanaka of Kyoto University.
- How to make: Introduce four genes called specific "Yamanaka factors" into "differentiated cells (mature cells)" collected from the patient's own skin or blood.
- Mechanism: Through this genetic manipulation, the cells are reset to an "immature state that can become anything" as if time had been wound back.
- Benefits: Because they can be made from one's own cells, immune rejection is less likely to occur, and because fertilized eggs are not used, the ethical hurdles were also cleared.
(4) Future medicine and safety challenges
Currently, the development of treatments using iPS cells to regenerate lost organs and tissues is progressing around the world. However, challenges remain. Some of the genes introduced to make iPS cells may include so-called "cancer genes," and how to suppress the risk of tumorigenesis after transplantation is at the forefront of research.
Also, research on a more advanced treatment that directly introduces Yamanaka factors into the body using a viral vector (carrier) to rejuvenate the cells in the body itself has begun, and rejuvenation of organs and extension of lifespan have been reported in mouse experiments.
Stem cells and iPS cells are now rewriting the future of medicine as the "ultimate tool" for stopping aging and regenerating lost functions.
5. What are the popular "rejuvenation drugs"?
Currently, substances that are said to "rejuvenate just by taking them" are being researched around the world, but here are three representative ones.
- Rapamycin: A substance known as an immunosuppressant that activates the cell's "self-cleaning function (autophagy)." An extension of lifespan of about 10% has been observed in mice, but side effects such as weakened immunity are also concerns.
- Metformin: It has a long history as a diabetes medication, but its effect of extending lifespan through its metabolism-improving action is also attracting attention. However, it requires caution because it shows toxicity if the dosage is not followed.
- NMN: This is the most talked-about substance right now. It has the role of increasing NAD, an enzyme essential for maintaining youth. Rejuvenation effects have been shown in Professor Shinichiro Imai's research, and many people take it as a supplement. However, warnings have been issued about the timing of taking it (morning is recommended, night may have the opposite effect) and the method of intake (intravenous injection may have the opposite effect).
6. Senolytics: Targeting senescent cells
Senescent cells cause a phenomenon called "SASP (senescence-associated secretory phenotype)," which secretes inflammatory substances that have a negative impact on surrounding normal cells. A treatment called "senolytics (senescent cell removal)" that pinpoint removes only these senescent cells is expected. Improvements in kidney function and physical function have been confirmed in mice. However, because senescent cells also play a role in healing wounds in some parts, it has also become clear that it is not simply a matter of completely eliminating them.
Let me explain in a little more detail.
What is senolytics
"Senolytics" is a word combining "senescent," meaning senescent cells, and "lytic," meaning destruction/decomposition.As the name suggests, "senolytic drugs" are drugs aimed at selectively finding and removing senescent cells accumulated in the body.
Why is it necessary to remove senescent cells
Senescent cells do not just stay there, but also release harmful inflammatory substances called "SASP (senescence-associated secretory phenotype)" and enzymes that break down collagen to their surroundings. This has a negative impact on surrounding normal cells and becomes a cause of further aging and the progression of age-related diseases such as cancer, dementia, and diabetes. In other words, the idea is to suppress aging and extend healthy lifespan by removing this "seed of inflammation."
Current status and possibilities of research
Currently, research is progressing to apply existing anticancer drugs, plant-derived components such as quercetin and fisetin, and even immune checkpoint inhibitors (such as Opdivo) as senolytics. In experiments using mice, the following effects have been reported.
- Improvement of physical function decline
- Improvement of kidney function
- Reduction of inflammation in the body
- Extension of average lifespan by about 6%
Important challenges
On the other hand, it has also become clear that it is not simply a matter of eliminating all senescent cells. In research, there have also been results where mice that completely removed senescent cells became worn out. Because senescent cells have necessary aspects for the body, such as being involved in "wound repair," killing everything blindly comes with risks. Therefore, it is thought that it will still take time for application as a safe and effective treatment.
7. Ayurveda and future prospects
Our research team is also paying attention to "Ayurveda," the traditional medicine of India. It has been discovered that plant components used in this medicine with 5000 years of history have the possibility of extending cell lifespan, and verification in mice is currently underway. It is a very interesting approach that combines the latest science and ancient wisdom.
Summary: The future of immortality and longevity
What can be understood through this explanation is that although rejuvenation research is steadily producing results at the mouse level, there are a mountain of challenges to be solved for application to humans, such as safety and the balance with lifestyle. Not only waiting for a magic drug, but first taking care of your current lifestyle can be said to be the best measure at this point.
* This article is intended to introduce research trends related to aging and rejuvenation to the general public, and does not guarantee the effects of specific treatments or products. For health concerns, please consult a medical institution.