Looking for the philosopher's stone: Emerging approaches to target the hallmarks of aging in the skin

Jun 17, 2024Journal of the European Academy of Dermatology and Venereology : JEADV

New ways to target key signs of skin aging

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Abstract

Increased ß-galactosidase activity and induction of p16 are early biomarkers of cellular senescence.

Cellular aging involves stress-induced damage and repair cycles, leading to either apoptosis or senescence.
Senescent cells exhibit a senescence-associated secretory phenotype (SASP), which includes over 80 pro-inflammatory factors.
The composition of the SASP can have both beneficial and harmful effects on processes like wound healing and tumor suppression.
Recent findings suggest that senescence might be prevented or delayed through lifestyle changes, senolytics, or senomorphics.
Tissue rejuvenation techniques, including stem cell stimulation and reprogramming of aged cells, are being explored as potential treatments for age-related diseases.

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Senescence and epigenetic alterations are two important hallmarks of cellular aging. During aging, cells subjected to stress undergo many cycles of damage and repair before finally entering either apoptosis or senescence, a permanent state of cell cycle arrest. The first biomarkers of senescence to be identified were increased ß-galactosidase activity and induction of p16. Another feature of senescent cells is the senescence-associated secretory phenotype (SASP), a complex secretome containing more than 80 pro-inflammatory factors including metalloproteinases, growth factors, chemokines and cytokines. The secretome is regulated through a dynamic process involving a self-amplifying autocrine feedback loop and activation of the immune system. Senescent cells play positive and negative roles depending on the composition of their SASP and may participate in various processes including wound healing and tumour suppression, as well as cell regeneration, embryogenesis, tumorigenesis, inflammation and finally aging. The SASP is also a biomarker of age, biological aging and age-related diseases. Recent advances in anti-age research have shown that senescence can be now prevented or delayed by clearing the senescent cells or mitigating the effects of SASP factors, which can be achieved by a healthy lifestyle (exercise and diet), and senolytics and senomorphics, respectively. An alternative is tissue rejuvenation, which can be achieved by stimulating aged stem cells and reprogramming deprogrammed aged cells. These non-clinical findings will open up new avenues of clinical research into the development of treatments capable of preventing or treating age-related pathologies in humans. INK4a

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Looking for the philosopher's stone: Emerging approaches to target the hallmarks of aging in the skin

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