The Problem
The skin is the one organ constantly visible to the signs of aging and unresolved inflammation.  The obvious external signs of skin aging are the loss of skin elasticity and thinning of the skin.  These visual signs result from increased cellular senescence in the skin (1-3).    

The Traditional Medical Approach
Retinol treatment, laser resurfacing, and collagen injections are the primary treatments to make the skin appear to look younger.  However, they don’t treat the underlying cause of aging skin, which is increased cellular senescence.

The Metabolic Engineering® Approach
The goal of Metabolic Engineering® is to activate AMPK in every organ, including the skin.  Using the Zone diet component of Metabolic Engineering® to restrict calories without hunger or fatigue is the most powerful dietary approach for increasing AMPK activity.  The omega-3 fatty acid dietary component of Metabolic Engineering® reduces inflammation and promotes its resolution.  The polyphenol dietary component of Metabolic Engineering® reduces oxidative stress.  Equally important is that the omega-3 fatty acid and polyphenol components of Metabolic Engineering® are also indirect activators of AMPK activity.   Thus, combining all three dietary interventions in Metabolic Engineering® provides the optimal dietary approach to maximizing AMPK activity to metabolize stored excess body fat for energy. 

Metabolic Engineering® works by activating AMPK.  Once AMPK is activated, it is the key to reducing the rate of aging (4,5).  AMPK activation reduces the release of pro-inflammatory cytokines by inhibiting the inflammatory gene transcription factor NF-κB (6).  Simultaneously, AMPK activation also enhances the activity of another gene transcription factor (Nrf2), increasing the production of anti-oxidative enzymes that reduce free radical damage (7).  This is why activating AMPK is the key to slowing the aging process in every organ, including the skin.

References
1. Chin T, Lee XE, Ng PY, Lee Y, Dreesen O.  The role of cellular senescence in skin aging and age-related skin pathologies.  Front Physiol. 2023; 14:1297637.doi: 10.3389/fphys.2023.1297637.

2. Wlaschek M, Maity P, Makrantonaki E, Scharffetter-Kochanek K. Connective tissue and fibroblast senescence in skin aging.  J Invest Dermatol.  2021; 141:985-992. doi: 10.1016/j.jid.2020.11.010.

3. Wyles SP, Carruthers JD, Dashti P, Yu G, Yap JQ, Gingery A, Tchkonia T, Kirkland J.Cellular senescence in human skin aging: Leveraging senotherapeutics. Gerontology. 2024; 70: 7-14. doi: 10.1159/000534756.

4. Salminen A and Kaarniranta K.AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network.  Ageing Res Rev. 2012; 11: 230-41. doi: 10.1016/j.arr.2011.12.005.

5. Ge Y, Zhou M, Chen C, Wu X, Wang X.Role of AMPK mediated pathways in autophagy and aging.  Biochimie. 2022; 195: 100-113. doi: 10.1016/j.biochi.2021.11.008.

6. Salminen, A., Hyttinen, J.M.T. & Kaarniranta, K. AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan. J Mol Med. 2011. 89: 667–676. doi.org/10.1007/s00109-011-0748-0

7. Manuel Matzinger, Katrin Fischhuber, Daniel Poloske, Karl Mechtler, Elke H. Heiss. AMPK leads to phosphorylation of the transcription factor Nrf2, tuning transactivation of selected target genes. Redox Biology.  2020: 29:101393. doi.org/10.1016/j.redox.2019.101393.