Humanity has long sought a method of living for eternity. We have created entire mythos reflecting our hopes of immortality from the vampire to the zombie, and our fear of death drives our nearly every action. Only recently have we begun to find solutions that may one day lead us to a greatly extended life.

 

As cells age and their genetic material becomes damaged, it is normal for them to release a protein trigger called p53 to initiate cellular apoptosis. Apoptosis is a cellular function that destroys the cell in response to damaged DNA to make room for new cells. However, when this process does not work correctly, it can lead to cancer, organ damage, and an array of other nasty effects.

 

Recent studies by Erasmus University and the Buck Institute for Research in Aging as well as the Sinclair Lab have shown some unique methods of dealing with cellular damage. The Sinclair Lab study, published in 2013, highlights a method of reversing DNA damage. The study led by Dr. Peter De Kaiser with Erasmus University and the Buck Institute for Research in Aging focuses on targeted elimination of senescent cells in the body.

 

What are senescent cells?

 

Senescent cells have sustained damage to their DNA, a status that would normally trigger the release of p53 and, subsequently, cell death. Senescent cells contain higher than normal amounts of DOXO4, which directly prevents the cells from beginning the process of apoptosis.

 

How do senescent cells inflict harm?

 

Senescent cells stick around–they do not begin apoptosis, but they also do not become cancerous. Cells that have undergone this transformation instead remain in a semi-dormant state, lingering around and secreting chemicals into the surrounding areas of the body–not good news for nearby cells.

 

How can Senescent Cells be Treated Before they Become a Serious Issue?

 

Senescent cells can be eliminated naturally by separating FOXO4 from p53, allowing the protein to do its job and initiate apoptosis. But how can these two things be separated at such a small scale with reliable accuracy? By introducing a cell-penetrating peptide. Cell-penetrating peptides are a fairly recent discovery and are showing significant promise in other areas of medicine.

 

Eliminate senescent cells to lengthen lifespan

 

In a study by the Mayo Clinic, mice who underwent gene therapy to have between half and three-quarters of their senescent cells terminated lived approximately 20% longer. The study led by Dr. Peter De Kaiser had similar results which included regrowth of and healthier fur as well as significantly increased organ function and energy levels.

 

Aging and DNA

 

As we grow old, our cells suffer damage as a result of our environment and their reproductive method alike. Telomeres exist at the end of chromosomes to prevent damage during cellular reproduction, but oftentimes, that is not enough. When cells sustain damage, we have a new way of ensuring that they are eliminated–one that is just a few years away from human trials.

 

A preemptive approach that repairs cellular damage may also become available in the near future. The Sinclair Lab of Harvard University has developed a method to reverse DNA damage. By adding NMN, a precursor to NAD+ into sample mice, they were able to kickstart their metabolism and revert them to a younger state of functionality.

 

How Does Aging Alter Metabolic and Muscular Function?

 

As mammals age, our muscles grow weaker, swell with inflammation, and do not work as well. Similarly, our cells lose the ability to communicate effectively between the nucleus and mitochondria, resulting in an inability of cells to reproduce effectively because a very small portion of the cell DNA resides exclusively in mitochondrial DNA.

 

By weakening the ability of the nucleus and mitochondria to communicate effectively, aging restricts the amount of carbohydrates we can process and turn into energy.

 

How can cellular damage and aging be reversed?

 

The Sinclair Lab study found that as mammals age, the concentration of NAD+ in their cells dropped off sharply. The mice in the study around 22 months of age had a much lower NAD+ concentration than mice around 6 months of age. In order to reverse this, NMN was added to their system, which transitioned into NAD+. The mice who were administered NMN became more active, had healthier coats, more youthful muscle tone, and more efficient metabolisms.

 

How Does NAD+ Fight Aging?

 

When higher levels of NAD+ were introduced to older mice, they exhibited an appearance and muscle tone similar to having consistently eaten healthily and exercised regularly–very similar to the physical state of the six-month old mice. SIRT-1 is an NAD+ dependent enzyme that works to protect individuals from metabolic decline, cancer, neurodegeneration, and cardiovascular disease. increased SIRT-1 expression with NAD+ has also been shown to extend lifespan in mice.

 

What do these studies mean together?

 

When the results of the studies are compared, we are left with two significant breakthroughs on the horizon–the ability to reverse damage to DNA at the molecular and cellular levels, as well as removing senescent cells from living organisms without harming healthy cells.  We may not have found the Fountain of Youth, but we are on the verge of much longer, healthier lives.