December 19, 2013

expert reaction to ageing in mice

Researchers publishing in Cell discovered a naturally produced compound rewinds aspects of age-related demise in mice.

Dr Lynne Cox, Lecturer in Biochemistry, University of Oxford, said:

“The authors of this wide-ranging paper describe a new biochemical pathway controlling energy production by the cell’s powerhouses, the mitochondria, in response to levels of a small chemical called NAD+ in the nucleus of the cell. They show how this cross-talk breaks down with age in mice. They study a large number of factors to piece together a jigsaw of protein interactions that are important for regulating energy production. In particular, they focus on an enzyme called SIRT1 and a factor that is usually found under low oxygen conditions, called HIF1alpha. Their results suggest that old muscle behaves as if it was starved of oxygen, and shifts energy production away from using oxygen to a pathway also used by cancer cells and also seen in human muscle cells in diabetes, and in the liver of mice fed a high fat diet.

“Perhaps the most interesting general observation is their use of a chemical to essentially reverse age-related declines in energy production by muscle cells. This chemical, NMN, is used by cells to make NAD+, the factor that they show earlier is important in maintaining the stability and function of the mitochondria. However, the changes they report at the biochemical level are not accompanied by an increase in muscle strength, so it’s not yet time to get over-excited about treating age-related muscle frailty in older humans. A much longer and more detailed study of the effects of NMN on muscle structure and function is now needed to test this preliminary finding.”

Dr Ali Tavassoli, Reader in Chemical Biology, University of Southampton, said:

“The work shows for the first time that some of the processes associated with ageing are triggered by biochemical changes in cells. Interestingly though, the process seems to be potentially reversible with a small molecule. The authors show that after treating mice for a week with a compound that generates NAD+ in cells, some of the cellular processes associated with ageing are reversed.

“It is important to note, that they did not see any changes in the mouse itself. This could be for one of two reasons; either they need to treat for longer so that the changes occurring in the cells have time to affect the whole organism, or alternatively, the biochemical changes by themselves are not sufficient to reverse the physical changes associated with ageing in the mouse. More experiments are necessary to see which of these cases are true.”

Professor Tim Spector, Professor of Genetic Epidemiology at Kings College, London, said:

“This is an intriguing and exciting finding that some aspects of the aging process are reversible.

“It is however a long and tough way to go from these nice mouse experiments to showing real anti-aging effects in humans without side effects.”

‘Declining NAD⁺ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging’ by Ana P. Gomes et al.  published in Cell on Thursday 19 December 2013.