science


improving the ageing process

The last decade has been thriving in discoveries related to ageing allowing us to treat it in a more systemic way. Different physiological components have been found to be linked to what we know as the effects of ageing. Our products formulation is carefully elaborated based on this science, it is also important for us to share this knowledge with you. We believe that a quick science class about longevity is preliminary to your good care.

the foundations of clidro .

NAD+, the essence .

Nicotinamide Adenine Dinucleotide (NAD+) is an indispensable coenzyme found in every cell. It is a critical tool for mitochondrial energy metabolism. NAD+ also assists several processes of biological activity regulation linked to a healthy human body such as circadian rhythms, the oxidative stress and the maintenance of DNA.

Unfortunately, NAD+ is not an unlimited resource and from your birth it can only decrease:

At 50 years old, you only have 50% of the amount in your cells that you used to have when you were 20 — at 80 years old this amount is between 1 and 10%. It is easy to correlate chronological age with NAD+ systemic decrease across multiple tissues.

NAD+ depletion [01] has been associated with hallmarks of ageing and may underlie a wide-range of age-related diseases, such as metabolic depletion [02], cancer and neurodegenerative diseases [03].

Further on this page we highlight why boosting NAD+ levels is our core therapeutic strategy to counter ageing-associated pathologies.

mitochondria, the powerhouse of life .

Cells are the building blocks of all known living organisms. The human body counts more than 10 trillions cells working in unison. They use nutrients and oxygen to execute the functions coded in their DNA and also communicate with each other with a multitude of messengers.

Mitochondria are small independent organisms living within the cytoplasm of each cell—their main role is to transform nutrients into energy.

With ageing, mitochondria become less efficient at producing energy while their count is decreasing. Older cells and thus organs have overall a lower vitality.

During the metabolic process mitochondria produce reactive oxygen species (ROS) which are free radicals that accumulate and rust the cell environment. ROS production increases with age and extracellular stress. Damages due to excessive ROS are common causes of injuries to cells and organisms. It has been shown that the prevalence of neurodegenerative diseases (ND) increases with ageing and oxidative stress has an intimate connection with ND. [01]

PARP-1, sirtuins and lifespan .

When the DNA is damaged, PARPs genes produce a group of proteins that rely upon NAD+ for reparation [01]. This process consumes a substantial amount of NAD+ to function [02]. With age, PARPs get more and more solicited, one of the reasons why NAD+ levels decrease drastically.

Similarly, sirtuins are a family of genes that have been recently linked to many aspects of age-induced damage regulation. It is at the core of many ageing theories. The proteins depending on NAD+ encoded by the SIRT genes control what your genes do by changing how the DNA is folded and expressed [03].

In humans, seven sirtuin family members exist, ranged from SIRT-1 to SIRT-7.

It has been documented that SIRT-1 protects against neurodegenerative disease, promotes liver function and regeneration, stem cell differentiation and reverses leptin resistance thus promoting weight loss [04].

SIRT-2 seems to promote longevity [5]. SIRT-2 synthesis is activated by the ratio of NAD+ : NADH (which is the reduced form of NAD+) within the cell. This ratio is naturally influenced by caloric restriction which has been demonstrated to increase lifespan in mice experiments [6].

While sirtuins levels decrease with age, studies show that their up-regulation alleviates the symptoms of ageing and cellular degeneration. Sirtuins seem to increase lifespan in yeast, mice and humans.

hypothalamus clock theory .

The hypothalamus schedules the body operation via the secretion of hormones to send signals to the body. For example, the hypothalamus is responsible for controlling the postural growth of children or triggering the onset of puberty and sexual maturity. Some researchers believe the hypothalamus keeps sending chemical signals to your body to age and eventually die [01].

The hypothalamus works as a clock, from your birth, puberty, sexual maturity, decline and death. Tricking the hypothalamus to believe that you are young would commit it to send the signals to keep you young. Growth hormones, neurotransmitters proteins such as orexin or neuropeptide y have a significant role in tissues quality over lifespans such as maintaining a good muscle mass, a low-fat mass or a solid bone density [02].

going further in the future .

ekei labs research .

Coping with the ageing process is like a symphony and ekei labs believe that NAD+ is the conductor of this orchestra.

Moreover our product line will diversify in the future. While time is at work we would like to give you an insight on the science about other ageing fields that are important to us.

Please keep in mind that the science explained in the paragraphs below is still hypothetical and will require more results to make a safe and efficient treatment that will target efficiently these biological aspects.

senescence as a consequence of untreated ageing .

As of all things, your cells get old but not all at the same pace. Once damaged or mutated, some of them stop dividing and enter a state of permanent growth arrest without dying to avoid transmitting their defaults to their daughter cells [01]. This process is called senescence and these “zombie cells”—not dead nor operating—emit signals that allow them to naturally be cleared by the immune system. But with time, the immune system doesn’t respond as good which leads them to accumulate and create cellular inflammation [02] to the other cells around them while consuming nutrients. Senescence is a consequence of ageing but also an aggravator [03].

Clearing the senescent cells has been shown to increase the lifespan of mice by 25% and ameliorate ageing conditions and have a positive action in wounds healing.

stem cells and tissues regeneration .

Stem cells are a kind of cells that did not yet differentiate into a specific tissue (e.g. muscle, neuron or liver cell) [01]. When our body gets injured they step-in to renew the damaged tissues [02].

To perpetuate a stem cells pool throughout life can self-renew. However, this process deteriorates over time [03] in some parts of the body—for example in the brain where neural stem cells can produce some type of neurons and glial cells (the neurons caretaker). This process is very important to prevent neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases.

Exciting scientific research [04] from August 2017 has found that the implantation of fresh stem cells in the hypothalamus [05] controls the speed of ageing in mice. It increased the hypothalamic production of a gene-expression agent called micro RNA and is transported via the cerebrospinal fluid throughout the nervous system and has been described as a mediator [06] of ageing in organs [07].

We see major potential in keeping the human stem cells pool healthy.

telomeres and dna erosion .

You can picture telomeres as the shoelace aglets of the DNA strands protecting your chromosomes from dislocation [01].

Each time a cell divides the genetic material from chromosomes is duplicated in two identical copies for the daughter cells while their telomeres are trimmed. After several divisions, the telomeres are too eroded leading the cell to either die or become senescent [02].

An enzyme named telomerase adds bases to the ends of telomeres. Telomerase remains active in sperm and eggs, which are passed from one generation to the next. If reproductive cells did not have telomerase to maintain the length of their telomeres, any organism with such cells would soon go extinct.

epigenome as the controller of dna expression .

Epigenetics refers to the modification that turns genes “on” or “off” during the lifetime of an individual. The genetic code itself stays intact, but the way the cells interpret the genes is changed by external factors such as the environment, lifestyle, disease or ageing [01].

University of California Los Angeles proposed a way to measure the “biological” age of subjects by observing their epigenome. This epigenetics clock was more accurate to guess the time of death of the subjects than their actual chronological age when associated with detailed conditions such as smoking habits, heart condition and body mass index. This study opens a new area where the epigenome could have a key role in ageing and taking care of it would help to slow down ageing [02].