Heard of senolytics?

Heard of senolytics?

Margie GanderDec 3, '19

When you look in the mirror, you don't want to see new wrinkles, right? You may even think about what is going on in the inside too! More philosophically, humans have always been interested in "why" we age and how we can live longer and healthier lives. 

Most recently, our pursuit of this question has led us to this new science called senolytics. 

What is senolytics?

Extending life has always fascinated human beings. I know that it appeals to me as I still have lots of traveling to do! 

Well, it would seem that with our greater understanding of genomics and human biochemistry, we could soon be able to swallow a pill that could help us to live forever. A  pill that could push back the ageing process – a medicine that could push back the fragility, osteoarthritis, memory loss, sagging skin and cancers that plague old age.

Enter the science of senolytics: an emerging – and highly anticipated – area of anti-ageing medicine. These scientists are focused on prolonging what they call “healthspan” than lifespan: this means helping people to age with less pain and illness, with a better quality of life. 

The science of senolytics is trying to unlock cellular senescence (defined as irreversible cell cycle arrest) which is driven by a variety of mechanisms, including telomere shortening, other forms of genotoxic stress, or mitogens (chemical substances, usually a protein, that induces a cell to begin cell division) or inflammatory cytokines. 

Their findings have led them to focus much of their research on the role of nucleotides in cellular health and stability.  The researchers observed that the senescent cells stopped producing nucleotides, the building blocks of DNA. When they took young cells and forced them to stop producing nucleotides, they became senescent or aged. This means that the production of nucleotides is essential to keep cells young. It also means that if we could prevent cells from losing nucleotide synthesis, the cells might age more slowly. Sounds incredible! 

Why does senescence occur?

Senescent cells accumulate as you age. The link between senescence, ageing, and age-related chronic disease, including cancer, neurodegeneration, and metabolic and cardiovascular diseases, has largely fueled the senescence research field. Senescence typically occurs in response to damaging stimuli, including telomere shortening (replicative senescence), DNA damage (DNA damage-induced senescence), and oncogenic signaling (oncogene-induced senescence).

DNA damage triggers the DNA repair machinery, apoptosis, or senescence depending on the extent of damage and physiological context. Persistent DNA damage and subsequent senescence can also be induced by ionizing radiation, chemotherapeutics, genotoxic stress, and oxidative stress. Now you know why you need to eat your fruit and veggies! 

What are nucleotides?

The four types of nucleotides in DNA are adenine, thymine, guanine, and cytosine. Purine and pyrimidine nucleotides fill a variety of metabolic roles. They are the “energy currency” of the cell. In addition to their roles as the subunits of nucleic acids, nucleotides have a variety of other functions in every cell: as energy carriers, components of enzyme cofactors, and chemical messengers.

Supplementing with nucleotides

Enhancing nucleotide metabolism protects against mitochondrial dysfunction and neurodegeneration.

Nucleotide balance is critically important not only in replicating cells but also in quiescent cells. Quiescence is the reversible state of a cell in which it does not divide but retains the ability to re-enter cell proliferation. Some adult stem cells are maintained in a quiescent state and can be rapidly activated when stimulated, for example by injury to the tissue in which they reside.

Telomeres and their role in senescence

Telomeres are the repetitive nucleotide sequences and associated proteins at the ends of chromosomes that serve as protective caps against chromosomal degradation.  

Disruption of mechanisms controlling telomere stability or length, such as mutations in proteins that form the telomerase complex, are associated with genomic instability, tissue damage, and cancer. Genetic disorders associated with defects in the telomere maintenance machinery are collectively referred to as telomeropathies.

The gene that encodes for telomere function is TERT. You can test for this gene in this DNA test:

 

 

With each round of DNA replication, telomeres are progressively shortened by 50-100 base pairs leading to senescence. During DNA synthesis, DNA polymerase is unable to fully replicate the end sequences on the strand which is known as the “end replication problem”. As a result, these unreplicated sequences are shortened. Once telomeres reach a critical length, the protective telomeric cap structure is disrupted and recognized by the cell as a DNA double-strand break, which triggers a persistent DNA damage response. This results in the halting of further cell division. 

You may wish to order this book if you want to learn more about telomeres and ageing:

 

When to take nucleotides and when to wait

When coaching, I like to use this table to help my clients decide when to "add-in" nucleotides for improved cellular health. 

Health Goal When to use Genotype
Athlete Enhance sports performance, recovery and endurance. 

Nucleocell Sport:

2 capsules, twice a day.

MnSOD
Post-chemotherapy 

Nucleocell IM to reduce senolytic action.

Research has shown that senescent cells accumulate in patients undergoing chemotherapy, presumably due to DNA damage, and are thought to contribute to unwanted side effects, particularly fatigue. Moreover, senescent cells can also contribute to cancer relapse and metastasis.

Due to nucleotide action, it is advised NOT to use while receiving chemotherapy treatment BUT rather once treatment has been concluded. 
Radiation treatment 
Nucleocell IM to reduce senolytic action.
Nucleotides can be taken during radiation treatment. 
Weight-loss
Bensulin is a dietary supplement for the maintenance of healthy blood glucose levels. In this product, specifically developed for people with type II diabetes and abnormal glucose homeostasis, a proprietary blend of Nucleotides (Nutri-tide™) has been combined with a very specific probiotic.  
Ideal for those who are overweight or struggle with insulin resistance.

 

PPARG

ADRB2

Energy 
Nucleocell IM 

MnSOD

Mitochondrial biosynthesis

Skin
Nucleocell IM helps to prevent accelerated ageing by halting senolytic action.
TERT
GUT health & immunity 
IntestAid-IB is a supplement for supporting long-term bowel health. It contains the nucleotide nutritional formula, a unique blend of the five nucleotides (Nutri-tide®) that are DNA building blocks, all of which are biologically available, plus glutamine, B vitamins and other nutrients.
Ideal for those who struggle with GUT health issues, GI inflammation, and immune regulation.
HMOX1

 

Order nucleotides online below:

 

On a personal note, I've recently starting adding-in nucleotide nutrition to my diet and I have experienced increased energy which is really great for a busy life!

Written by:

Marguerite Doig-Gander
CEO of MY DNA CHOICES
BA (Speech, Hearing & Lang Therapy) Hons | FMCHC | ReCODE Coach | Men's Health |  HMX Genomics & Biochemistry (Candidate)