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Pioneering researchers consider ageing to be a pathology that can be treated at a multimodal level. We highlight David Sinclair, prestigious Australian biologist and Harvard researcher and pioneer in the description of the genetic pathways that control ageing, who reaffirms that “There is no law that says we have to grow old”.
In recent years there has been an unprecedented advance in anti-ageing research and, among other things, it has been discovered that the rate of ageing is controlled by various genes and biochemical processes. This is Sinclair’s main point of study and this is the origin of the concepts of biological and chronological age. If we correctly stimulate the genes that control ageing, our biological age (the age shown by our cells) can be lower than that indicated by our ID card (chronological age).
Which genes control ageing?
There are many interrelated factors that regulate ageing. Among the most notable are these 3 genes:
|Important to know:|
DNA contains all the information needed to make proteins. They are responsible for carrying out cellular functions. This is why we will refer to a protein (e.g. enzymes) or the gene that codes for it (which usually has the same name as the protein).
This first gene, mTOR (mammal Target Of Rapamycin) is activated in response to protein (amino acid) intake. This pathway has a dual function: when there is an abundance of food, it activates much-needed processes such as muscle building and energy burning, among others. On the other hand, when there is a food deficit (e.g. through fasting) it activates other longevity-related pathways such as the autophagy mechanism (a cell renewal process by which cells recycle defective proteins). In addition, the activity of the mitochondria, which are responsible for generating ATP (biochemical energy for our body), is enhanced.
The second group is AMPK, (AMP-activated kinase). This enzyme is a low-energy sensor and is activated by reduced intake and low ATP, which increases its antagonist, AMP (hence the name).
Its main function is to generate more mitochondria that activate ATP synthesis. This process is anti-ageing as we lose mitochondria as we age.
In addition, its activation makes us more sensitive to insulin and allows us to avoid peaks in blood glucose that are so harmful to our bodies.Thus, to promote longevity, we need to increase its activity.
Additionally, AMPK activation leads to mTOR (the upstream pathway) inhibition and thus autophagy activation, thereby enhancing anti-ageing effects.
In humans it is a group of 7 genes that are activated in response to low energy or low amino acid levels, i.e. when we do not eat. Lack of food activates the enzyme NAMPT (nicotinamide phosphoribosyltransferase) which synthesises NAD (the “petrol” that sirtuins need to carry out their functions) from nicotinamide (vitamin B3). Read more about this mechanism in our post on Resveratrol and Quercetin.
Activating sirtuins promotes longevity: it repairs DNA, stabilises the genome, promotes mitochondrial and energy synthesis, reduces inflammation and eliminates harmful free radicals.
In addition, its activation leads to an interaction with the two pathways described above. AMPK is increased and mTOR is inhibited.
Scientific evidence has proven that there are several natural molecules that work and help improve our health and prolong our lives. These are called calorie restriction mimetics. They have the same beneficial effects as eating less (described in the previous section) regarding the genes that control ageing.
Here are some of the anti-ageing compounds that you can obtain from Zenement and that David Sinclair includes in his daily routine, along with their main features, dosage and recommended daily schedule(*).
|Molecule||Intervening pathway||Main function||Dose||Daily schedule|
|Spermidine||mTOR||Autophagy activation||0.5 – 2 mg||In the morning or evening|
|Glucose and cholesterol reductionand mitochondrial synthesis|
Morning, afternoon or evening
|Activation of DNA repair|
250 – 2000 mg
Morning or midday
|Senolytic, antioxidant and anti-inflammatory effect|
1000 mg máx.
|Morning or midday|
You can find out more about these anti-ageing compounds in our posts on spermidine, berberine, resveratrol and quercetin. We also invite you to visit our blog post “9 tips to delay ageing, live longer and better” in which we review some recommended habits for healthy ageing.
Most of the information contained in this article has been taken from David Sinclair’s Lifespan podcast series.