Long-term cysteine fortification impacts cysteine/glutathione homeostasis and food intake in ageing rats

Eur J Nutr. 2014 Apr;53(3):963-71. doi: 10.1007/s00394-013-0600-0. Epub 2013 Oct 18.

Abstract

Purpose: Healthy ageing is associated with higher levels of glutathione. The study aimed to determine whether long-term dietary fortification with cysteine increases cysteine and glutathione pools, thus alleviating age-associated low-grade inflammation and resulting in global physiological benefits.

Methods: The effect of a 14-week dietary fortification with cysteine was studied in non-inflamed (NI, healthy at baseline) and in spontaneously age-related low-grade inflamed (LGI, prefrail at baseline) 21-month-old rats. Fifty-seven NI rats and 14 LGI rats received cysteine-supplemented diet (4.0 g/kg of free cysteine added to the standard diet containing 2.8 g/kg cysteine). Fifty-six NI rats and 16 LGI rats received a control alanine-supplemented diet.

Results: Cysteine fortification in NI rats increased free cysteine (P < 0.0001) and glutathione (P < 0.03) in the liver and the small intestine. In LGI rats, cysteine fortification increased total non-protein cysteine (P < 0.0007) and free cysteine (P < 0.03) in plasma, and free cysteine (P < 0.02) and glutathione (P < 0.01) in liver. Food intake decreased over time in alanine-fed rats (r² = 0.73, P = 0.0002), whereas it was constant in cysteine-fed rats (r² = 0.02, P = 0.68). Cysteine fortification did not affect inflammatory markers, mortality, body weight loss, or tissue masses.

Conclusion: Doubling the dietary intake of cysteine in old rats increased cysteine and glutathione pools in selected tissues. Additionally, it alleviated the age-related decline in food intake. Further validation of these effects in the elderly population suffering from age-related anorexia would suggest a useful therapeutic approach to the problem.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Animals
  • Anorexia / blood
  • Anorexia / immunology
  • Anorexia / metabolism
  • Anorexia / prevention & control*
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antioxidants / adverse effects
  • Antioxidants / metabolism
  • Antioxidants / therapeutic use*
  • Appetite Regulation*
  • Cysteine / adverse effects
  • Cysteine / blood
  • Cysteine / metabolism
  • Cysteine / therapeutic use*
  • Dietary Supplements* / adverse effects
  • Energy Intake
  • Enteritis / blood
  • Enteritis / immunology
  • Enteritis / metabolism
  • Enteritis / prevention & control
  • Glutathione / metabolism*
  • Hepatitis / blood
  • Hepatitis / immunology
  • Hepatitis / metabolism
  • Hepatitis / prevention & control
  • Homeostasis
  • Inflammation Mediators / blood
  • Inflammation Mediators / metabolism
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestine, Small / immunology
  • Intestine, Small / metabolism
  • Liver / immunology
  • Liver / metabolism
  • Male
  • Oxidative Stress
  • Rats, Wistar

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Inflammation Mediators
  • Glutathione
  • Cysteine