Can I reverse aging? Can I grow younger again?

Slowing down aging is great, but what about actually reversing aging?

Reversing aging would mean making an old organism young again. Is it possible?

What may come as a surprise to many, the answer is yes! In the last few years, scientists have shown that it’s actually possible to partially reverse aging: they succeeded in making old organisms younger.
There are many ways to do this, via cutting-edge biotechnologies, and – to a lesser extent – via specific lifestyle interventions.

Let’s start with a few biotech approaches to reverse aging, before we cover lifestyle interventions.

EPIGENETIC REJUVENATION


The epigenome is the intricate molecular machinery that determines which genes are switched on or off. The older we get, the more the epigenome gets dysregulated. For example, cancer promoting genes are switched on (increasing our risk of cancer), and housekeeping and protective genes are switched off. This epigenetic dysregulation is one of the causes of aging.

However, it’s possible to reprogram this dysregulated, old epigenome back to a younger state.

This can, for example, be done by upregulating in a cyclical way (not continuously) four specific Yamanaka factors (R). These Yamanaka factors are proteins that can change the epigenome in cells. Yamanaka factors have been previously used to convert differentiated cells, like skin cells, neurons or muscle cells into stem cells (R), a ground-breaking discovery for which the Nobel Prize was awarded (R).

The Yamanaka factors can reprogram differentiated cells (non-stem cells) by changing the epigenome.

Scientists discovered that when Yamanaka factors are upregulated only for a short while in animals, their cells also became younger (a bit more “stem cell-like”), in the sense that their organs were better able to regenerate, and many other aging symptoms were undone or drastically reduced (R).

Other studies discovered that instead of using four Yamanaka factors, also three Yamanaka factors can be used to reprogram cells (R), and that even other transcription factors can be used, like Mxx1 (R).

This kind of epigenetic reprogramming approach to aging is called “epigenetic rejuvenation”.

CLEARING SENESCENT CELLS


Another way to make old animals younger again is by clearing away senescent cells.

The older we get, the more senescent cells accumulate in our body. These “zombie” cells refuse to die and secrete many harmful substances that damage the healthy neighboring cells.

Senescent cells in the skin contribute to a sagging skin, senescent cells in blood vessel walls contribute to stiffer blood vessels, senescent cells in the liver, fat and pancreas impair metabolic function, and so on. Cellular senescence is one of the reasons why we age.

In one experiment, senescent cells were removed in old mice. These old mice looked younger again: their gray fur with bald spots became shiny and black again, and the organs and other tissues of these mice could regenerate or function better compared to when they were old (R).

Image: The mouse at the top is old, the same mouse at the bottom looks younger after senescent cell clearance (Picture by Peter De Keyser, Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging, Cell, 2017)

Other studies show that when senescent cells are destroyed, various aspects of aging can be improved (R,R,R).

CAN WE REVERSE AGING IN HUMANS?

Previous studies were done in mice. The approaches we just mentioned are currently being developed to also be used in humans, but this will take many years (probably at least 15 years before we will see these technologies being used in humans).

So, the ultimate question is, is it possible to partially reverse aging in humans now?

Some studies have shown that it could already be possible to reverse aging in humans. At least when measured by epigenetic clocks.

Epigenetic clocks try to measure our real, biological age – so, how old you really are. One can be 50 years chronologically, but if you eat unhealthy and don’t exercise a lot, you can be biologically 58 years old.  This is what epigenetic clocks try to measure.

Epigenetic clocks look at the methylation patterns in our DNA. One way that the epigenome works is by putting small molecules, called methyl-groups, on the DNA. The more the DNA is covered with these methyl molecules, the less active the gene is (a gene is a piece of DNA containing the building instructions for a protein).

One study showed that giving growth hormone, metformin and DHEA reversed the epigenetic clock a little bit, making the participants younger again. During the year that the study lasted, they reversed aging by 1.5 years (R).

Other studies show that lifestyle interventions, including diet, exercise and supplements can reverse aging measured by epigenetic clocks.

In one study, patients were put on a healthy diet, had to take specific supplements and exercise. After 8 weeks, their epigenetic age was reversed by almost 2 years (R).

Other studies show that people are epigenetically younger by adhering to a healthy diet, regular exercise, stress reduction, moderate alcohol consumption, and so on (R,R).

We compiled 60 tips to slow down and even partially reverse aging here.

REVERSING AGING-RELATED DISEASES

These and other studies show that aging can be reversed. And not just aging, but also various aging-related diseases at the same time.

For example, if people adhere to a very healthy diet, many cases of type 2 diabetes can be reversed, and even atherosclerosis. In one study, people who adhered to a more healthy diet, and had to exercise could reduce the atherosclerotic plaque in the coronary arteries of their heart, not needing a heart operation anymore (which they were recommended to undergo) (R).

And even despite these impressive results, these study interventions (read: diets) can be further improved upon.

Even early stage Alzheimer’s disease can be reversed or substantially slowed-down if people start to eat and live healthier (R,R). We compiled various tips to reduce your risk of Alzheimer’s disease here.

In other words, it’s never too late to start to eat healthy, take supplements, exercise, fast and implement many other things that can not only slow down aging, but actually make you a bit younger again!