Oxidative stress and ageing: is ageing a cysteine deficiency syndrome?

Abstract

Reactive oxygen species (ROS) are constantly produced in biological tissues and play a role in various signalling pathways. Abnormally high ROS concentrations cause oxidative stress associated with tissue damage and dysregulation of physiological signals. There is growing evidence that oxidative stress increases with age. It has also been shown that the life span of worms, flies and mice can be significantly increased by mutations which impede the insulin receptor signalling cascade. Molecular studies revealed that the insulin-independent basal activity of the insulin receptor is increased by ROS and downregulated by certain antioxidants. Complementary clinical studies confirmed that supplementation of the glutathione precursor cysteine decreases insulin responsiveness in the fasted state. In several clinical trials, cysteine supplementation improved skeletal muscle functions, decreased the body fat/lean body mass ratio, decreased plasma levels of the inflammatory cytokine tumour necrosis factor alpha (TNF-alpha), improved immune functions, and increased plasma albumin levels. As all these parameters degenerate with age, these findings suggest: (i) that loss of youth, health and quality of life may be partly explained by a deficit in cysteine and (ii) that the dietary consumption of cysteine is generally suboptimal and everybody is likely to have a cysteine deficiency sooner or later.

The Global Regulator Spx Functions in the Control of Organosulfur Metabolism inBacillus subtilis

“…Secondly, microarray transcriptome analysis reveals that transcript levels of genes required for cysteine synthesis, the yrrT operon and cysK, increase when Spx interacts with RNAP (34). The stimulation of homocysteine production and transsulfuration is characteristic of cells responding to oxidative stress (4,12,21,28,29,37,39,47). In mammalian systems, cysteine production is accelerated during bacterial infection because of an increased need for glutathione.…”

An increased need for dietary cysteine in support of glutathione synthesis may underlie the increased risk for mortality associated with low protein intake in the elderly

“…Droge and colleagues have pioneered the notion that aging may be Ba cysteine deficiency syndrome^and have conducted several clinical trials in elderly subjects to document this (Droge et al 2006;Hauer et al 2003;Droge 2005). They report that NAC supplementation (600 mg t.i.d.)…”

“…increased muscle strength, raised serum albumin, and lowered serum TNF-alpha. They provocatively hypothesize that Bpractically everyone experiences sooner or later an ageing-related deficit in the body cysteine and glutathione reservoirs that warrants cysteine supplementation^ (Droge 2005).…”

p53, Oxidative Stress, and Aging

“…In further support of the notion that oxidative stress is an inducer of aging, treatment with antioxidants can increase the life spans of various organisms and has a beneficial impact on aging-related diseases (6,29,38,57,114,119). A low dose of dietary supplement with antioxidants partially mimics the effects of caloric restriction and delays aging in mice (6), and long-term treatment with free radical scavenging Schisandrin B, a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, delays aging-related functional impairment in various organs and improves the survival rate of aging mice (114).…”