Why do we age? identified 9 biological causes

Article by Alberto Beretta Presidente e Direttore Scientifico di SoLongevity

Why do we age?

Complex though it may be, today an answer can be given. In fact, there are at least nine. In fact, an international team of researchers has identified nine key mechanisms (hallmark) of ageing in animal species, including humans. As scientists report in their study published in Cell, these mechanisms are:
  1. The genome instability, as such as the progressive accumulation of damage (mutations) in DNA caused by external agents, such as certain harmful chemicals, pollutants, ionizing radiation, smoke and so on. Over time, cells lose the ability to repair them and these mutations cause significant functional damage to the cells until tumor degeneration.
  2. The shortening of telomeres, the final parts of chromosomes which, like caps, protect the DNA (making it more stable) but which “wear out” at each cell division. The discovery of the link between telomere shortening and aging has won the Nobel Prize for Medicine and Physiology to Australian biochemistry Elizabeth Blackburn in 2009 and biologists Elizabeth Blackburn, Carol Greider e Jack Szostak. Telomeres, the final parts of chromosomes, protect the DNA but “consume” at each cell division.
  3. Epigenetic alterations, biochemical reactions that control the ” switching on” and “switching off” of genes, also affecting the ability to repair DNA damage. These genetic activities are environmental and lifestyle sensibile, even if reversible.
  4. Loss of healthy protein (proteostasis). All cells have mechanisms of “quality control” of the proteins that are manufactured and that contribute to cellular functions. If a protein is defective or altered in any way to lose its original function, the cells discard it. When the “cleaning” mechanisms do not work properly, the damaged proteins accumulate and create damage that may be permanent.
  5. Alterations within the metabolic mechanisms that allow the correct perception of nutrients requirement. The best known example is the loss of response to insulin (insulin resistance), the antechamber of diabetes. In order to control blood glucose, the cells of the pancreas are forced to produce more and more insulin until they run out of stock. Insulin resistance is closely linked to other mechanisms of ageing, first and foremost chronic latent inflammation (inflammaging). Mitochondrial dysfunction is one of the 9 causes (hallmarks) of ageing.
  6. The dysfunctions of the mitochondria, the organelles that represent the energy centre of the cell. The mitochondria contain their own DNA (which is inherited only by motherhood) with a limited number of genes that however perform very important functions. The mitochondrial DNA is constantly subject to damage from oxidative stress, because the reactions that take place in the mitochondria constantly produce free radicals that damage the DNA and the proteins that constitute the mitochondria themselves.
  7. The cellular senescence is an independent mechanism from the previous ones, allowing an accumulation of “zombie cells” that inflame the tissues. Although they no longer function, in fact, these cells do not die because they have lost the ability to self-eliminate at the end of their life cycle, hence the name “zombies”. They represent a small fraction of all cells that make up tissue, but they cause damage to surrounding cells by producing inflammatory factors (cytokines) which in turn create an inflammatory microenvironment that damages the tissue itself.
  8. The loss of tissue regenerative capacity linked to the depletion of the stem cells, source of adult (differentiated) cells that build up organic tissues architecture and specialize their function. The mechanisms underlying stem cell depletion are multiple, but the answer to this problem is not as complicated as it might seem.
  9. The intracell communication alteration, with the production of inflammatory molecules. It is one of the most studied mechanisms of ageing, also called inflammaging, and it is also one on which it is possible to intervene effectively with lifestyle interventions (diet and moderate regular exercise) and with targeted nutritional supplements.

Not only DNA

The accumulation of DNA damages has historically been considered to be the main ageing cause and the one that is most difficult to intervene on. The first good news is that, on the other hand, cells already possess mechanisms capable of preventing these damages and possibly repairing them. It is therefore clear that ageing is a multidimensional phenomenon, which also involves the immune and hormonal system. And, out of the nine listed mechanisms, epigenetic ones seem to play a central role. All the others, in fact, can be linked to the malfunctioning of epigenetic control systems. It is not by chance that today there is increasing talk of “epigenetic ageing” or epigenetic drift, as proposed by David D. Sinclair , professor of genetics at Harvard Medical School and co-director of the Paul F. Glenn Center for the Biology of Aging, in the book “Lifespan”. And there’s more. An interesting characteristic of the underlying causes of ageing is their close interdependence: the different mechanisms, in fact, influence each other. This means that if you improve even on one of them, all the others will automatically improve. And here the second good news comes: epigenetics is easily influenced by lifestyles, and research has identified molecules of natural origin, drugs and targeted interventions capable of restarting its mechanisms.

Epigenetics is easily influenced and research has already discovered how to do it.

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