PYCR1 is a gene involved in the synthesis of proline – a common amino acid involved in metabolism. The protein encoded by PYCR1 is an mitochondrial Pyrroline-5-carboxylate reductase 1 – an oxidoreductase enzyme – that catalyzes the NAD(P)H-dependent conversion of pyrroline-5-carboxylate to proline. As far as skin aging is concerned, PYCR1 is an anti-wrinkle gene. The Role of PYCR1 in maintaining healthy skin and in premature skin aging rely on the two facts that

1) Collagen – the skin structural protein in the extracellular matrix of the dermal connective tissue – is abundant in proline and hydroxyproline with the common motifs of “Glycine-Proline-X and Glycine-X-Hydroxyproline”; Disruption of proline metabolism will affect collagen production in the dermis.

2) L-proline + NAD(P)+ 1-pyrroline-5-carboxylate + NAD(P)H + H⁺

The reaction catalyzed by Pyrroline-5-carboxylate reductase is a redox reaction that generate electrons. The electrons can enter the electron transport chain on mitochondria membrane in the cellular respiration (oxidative metabolism) to produce ATP – the energy molecule and product of the cellular respiration that are required for many cellular and metabolic process. Metabolic imbalance and cell energy reduction has long been suggested to impair skin’s renewal and repair capacity.

Mutations in the PYCR1 gene was found to cause the rare genetic condition that results in premature skin aging known as “wrinkly skin syndrome,”. This finding suggest that by increasing levels of the PYCR1 protein, fast aging and wrinkly skin can be reversed and treated and that there are genes whose function is to maintain youthful skin. Mutations and disruptions of these genes triggered by intrinsic and extrinsic factors will cause premature skin aging such as wrinkly skin syndrome. PYCR1 gene is a gene located at mitochondria – the cellular energy house. Changes in mitochondrial morphology and cell death in the skin connective tissues of individuals with PYCR1 gene mutation were also observed suggesting that PYCR1 is anti-apoptotic.

Using bioinformatics tools, scientists analyzed DNA samples collected worldwide from patients with symptoms of premature aging at a young age. The PYCR1 gene on chromosome 17 of these patients were found to be defective. There are specific mutations in the gene that led to aging signs of skin commonly seen in elderly people such as skin laxity and wrinkling. It was determined that skin and bone are the two tissues most severely affected in patients with wrinkly skin syndrome due to the fact that both skin and bone contain high levels of the PYCR1 protein under normal circumstances, suggesting that developing therapies that could increase the activity of the PYCR1 protein could possibly reverse the process of (skin) aging in affected individuals or slow it down in normal people. Age-defying and anti-wrinkling treatments for common disorders related to aging may be developed by maintaining and/or increasing proline metabolism.