Why do we grow old? 3 more biological mechanisms unveiled

Article by SoLongevity Research
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In 2013, nine causes of aging had been explained. About ten years later, the number rises to 12

What this article is about

– To the nine causes of aging described in the previously, today, three more have been added

– Inflammaging, already considered as an upstream process of one of the 9 hallmarks previously identified, is now counted as a mechanism in its own right

– The other two new hallmarks are deactivation of autophagy processes and dysbiosis, or loss of balance of the gut microbiota

In 2013, a research team led by cell biologist Guido Kroemer had identified nine mechanisms-hallmarksthat underlie the aging process. Recently, in early 2023, the same research group published a new paper in the scientific journal Cell, with which it identifies three new hallmarks:chronic low-grade inflammation (or inflammaging), deactivation of macroautophagy, and dysbiosis (alteration of the gut microbiota ). Let’s see what this is all about and what are the connections between these three new mechanisms and the nine previously described.


Chronic low-grade inflammation, or inflammaging, is characterized by the progressive accumulation of tissue damage. Its onset may be related to multiple causes, including the production of proinflammatory cytokines by senescent cells, as well as impaired autophagy, which is the reduced ability of cells to eliminate damaged proteins or other waste products. These alterations stimulate theNLRP3 inflammasome, a multiprotein complex that is activated in response to stress of various types, including mitochondrial oxidative stress, thus triggering an inflammatory response. The latter, in turn, increases the risk of occurrence of various diseases, including type 2 diabetes, atherosclerosis, and cancer.

In general, inflamed tissue causes, often asymptomatically, generalized inflammation and altered red-ox status of our cells. In addition, it was observed that age-associated inflammation inhibits epidermal stem cell function, which further supports the intricate interdependence of hallmarks contributing to the aging process: in fact, stem cell depletion was another of the first nine mechanisms identified and described in the 2013 publication.

On mechanisms related to inflammaging, as on other hallmarks, effective action can be taken through physical activity, through proper nutrition, and with nutritional supplementation.

Deactivation of macroautophagy

Another hallmark of aging is the loss by cells of the ability to implement “autophagic” (or “macroautophagic”) processes, those that allow them to eliminate damaged proteins or other macromolecules, or even entire organelles that are no longer able to perform their functions.

According to the recent publication by Kroemer’s group, the expression of certain genes related to the autophagic capabilities of our cells (including ATG5, ATG7 and BECN1, which code for the expression of proteins necessary for the regulation of the autophagic process) decreases with advancing age. This leads to a progressive accumulation of damaged products within the cell, which underlies cellular aging and the onset of serious diseases typical of old age, such asAlzheimer’s.

Dysbiosis of the microbiota

Finally, here we come to the new 12th hallmark of aging: dysbiosis. In recent years an increasing number of studies are bringing attention to the importance of the gut microbiota in maintaining our overall health. The microbiota consists of billions of microorganisms belonging to different species and performs many functions: it helps us digest and absorb certain nutrients, protects us from infection, and generally plays an important role in controlling inflammatory processes. Its alteration (dysbiosis, precisely) can in fact contribute to the onset of many different diseases includingobesity, type 2 diabetes, some neurodegenerative diseases and the development of neoplasms.

As we age, unfortunately, the biodiversity of our microbiota tends to decline. As with all other hallmarks of aging, knowing their potential and importance will help identify possible new intervention strategies.

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