Pgc-1α controls epidermal stem cell fate and skin repair by sustaining NAD homeostasis during aging.

Objective: The epidermal barrier is renewed by the activation, proliferation, and differentiation of keratinocyte stem cells after injury and aging impedes this repair process through undefined mechanisms. We previously identified a gene signature of metabolic dysfunction in aged murine epidermis, but the precise regulators of epidermal repair and age-related growth defects are not well established. Aged mouse models as well as mice with conditional epidermal loss of the metabolic regulator peroxisome proliferator-activated receptor gamma coactivator-1 alpha (Pgc-1α) were used to explore the cellular pathways which control skin repair after injury and stress.

AMPK Inhibits mTOR-Driven Keratinocyte Proliferation after Skin Damage and Stress.

Epidermal keratinocytes (KCs) rapidly proliferate to repair the skin barrier, and a strict control of division is necessary for healthy tissue homeostasis. However, the pathways that restrain proliferation after epidermal stress are not known. AMPK is an important signaling mediator of energy metabolism previously associated with skin stress and cancer; yet, its explicit impact on KC growth is not known.

Genetic deletion of mast cell serotonin synthesis prevents the development of obesity and insulin resistance.

Obesity is linked with insulin resistance and is characterized by excessive accumulation of adipose tissue due to chronic energy imbalance. Increasing thermogenic brown and beige adipose tissue futile cycling may be an important strategy to increase energy expenditure in obesity, however, brown adipose tissue metabolic activity is lower with obesity. Herein, we report that the exposure of mice to thermoneutrality promotes the infiltration of white adipose tissue with mast cells that are highly enriched with tryptophan hydroxylase 1 (Tph1), the rate limiting enzyme regulating peripheral serotonin synthesis.

The exercise cytokine interleukin-15 rescues slow wound healing in aged mice.

Impaired wound healing in elderly individuals increases infection risk and prolongs surgical recovery, but current treatment options are limited. Low doses of interleukin-15 (IL-15) that mimic exercise responses in the circulation improve skin structure and increase mitochondria in uninjured aged skin, suggesting that IL-15 is an essential mitochondrial signal for healing that is lost during aging. Here we used gene microarray analysis of old and young murine epidermal stem cells and demonstrate that aging results in a gene signature characteristic of bioenergetic dysfunction.