Article

Mitochondria and ageing: winning and losing in the numbers game.

Centre for Integrated Systems Biology of Ageing and Nutrition, Henry Wellcome Laboratory for Biogerontology Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
BioEssays (impact factor: 4.95). 10/2007; 29(9):908-17. DOI:10.1002/bies.20634 pp.908-17
Source: PubMed

ABSTRACT Mitochondrial dysfunction has long been considered a key mechanism in the ageing process but surprisingly little attention has been paid to the impact of mitochondrial number or density within cells. Recent reports suggest a positive association between mitochondrial density, energy homeostasis and longevity. However, mitochondrial number also determines the number of sites generating reactive oxygen species (ROS) and we suggest that the links between mitochondrial density and ageing are more complex, potentially acting in both directions. The idea that increased density, especially when combined with mitochondrial dysfunction, might accelerate ageing is supported by a negative correlation between mitochondrial density and maximum longevity in an interspecies comparison in mammals, and by evidence for an intimate interconnection between cellular ROS levels, mitochondrial density and cellular ageing. Recent data suggest that retrograde response, which activates mitochondrial biogenesis, accompanies cellular ageing processes. We hypothesise that increased mitochondrial biogenesis, and possibly also impaired degradation and segregation of mitochondria, if occurring as adaptation to pre-existing mitochondrial dysfunction, might aggravate ROS production and thus actively contribute to ageing.

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Keywords

activates mitochondrial biogenesis
 
ageing process
 
aggravate ROS production
 
cellular ageing
 
cellular ageing processes
 
cellular ROS levels
 
energy homeostasis
 
increased density
 
increased mitochondrial biogenesis
 
interspecies comparison
 
intimate interconnection
 
maximum longevity
 
mitochondrial density
 
Mitochondrial dysfunction
 
mitochondrial number
 
pre-existing mitochondrial dysfunction
 
reactive oxygen species
 
Recent data
 
Recent reports
 
retrograde response