Masterminds of skin aging and disease unmasked—scientists map key culprits and plot prevention-therapy roadmap

 The skin, together with hypodermis which contains subcutaneous fat is the body's largest organ. Like most other organs, skin is a dynamic organ subject to constant cell death and regeneration involving skin stem cells with an epidermal cell renewal cycle of 3-4 weeks. The dermal and epidermal skin cells express most elements that regulate hypothalamus-pituitary-adrenal axis activities along with their corresponding receptors, in addition to producing catecholamines, acetylcholine and many other neurotransmitters. Thus, similar to the brain, skin has its own neuroendocrine system, which communicates within itself and with systemic humoral and neural pathways to induce vascular, immune, or pigmentary alterations to buffer or adapt to noxious factors and neutralize provoked local reactions. Melanocytes regulated by hormonal and neurotransmitters can also modulate local homeostasis in response to UV radiation, other biological factors and stress, says Dr. Abdolmaleky. 

An unhealthy lifestyle, including smoking, malnutrition, lack of exercise, and psychological stress, affect skin stem cells function and induce skin aging or skin diseases. Hormonal imbalances and rapid changes in hormone levels, especially during puberty and menopause, may influence the activity of skin stem cells, and induce skin diseases or accelerate skin aging. Additionally, chronic skin inflammation, either due to external factors, aging, or underlying health conditions, impairs the function and trigger skin stem cell degeneration. Besides active genes of skin stem cells shown in the following figure, other genes such as collagens and TGF-β are involved in the health of differentiated skin cells. For instance, subsequent to chronic sun exposure, excessive TGF-β expression alters collagen composition inducing photoaging and wrinkle formation.

The skin microbiota, composed of trillions of microorganisms, which differs by the skin sites and age preserve a protective barrier, defend against pathogens, prevent moisture loss and maintain skin’s slightly acidic pH, ranging from 4.7 to 5.5. Excessive sun light or UV radiation, pollution, and toxins can alter the healthy skin microbiome composition leading to skin diseases, says Dr. Zhou, from the BIDMC, Harvard Medical School. He also describes how gut microbiota has important effects on skin health by producing short chain fatty acids with anti-inflammatory effects. Psoriasis and alopecia areata, atopic dermatitis and acne are linked to gut dysbiosis. Specific bacterial taxa associated with higher levels of pathogenic autoantibodies are also linked to Pemphigus. The authors finically conclude that maintaining a healthy skin and gut microbiome through a balanced diet rich in fiber, phytochemicals, fermented foods, and specific probiotics or prebiotics (that promote the growth of beneficial microorganisms), and postbiotics (metabolic byproducts of probiotics) may promote overall well-being and enhance skin health.