Energy metabolism, nutrition and ageing

Energy metabolism and nutrition have long been suggested to play a role in ageing processes, in age-related disease and in the health of the elderly. This review addresses new insights arising from selected studies of the interplay of these factors. Data on overfeeding and underfeeding in young versus elderly men and women demonstrate a deficit with age in the ability to regulate energy balance. They also indicate that current values of Recommended Daily Allowances of caloric intake underestimate the needs of the elderly. The studies suggest that diminished capacity of energy metabolism with age may have a nutritional component and the involvement of the central nervous system. The contribution of peripheral tissues is suggested by studies of mitochondrial DNA isolated from tissues of humans and rodents. The studies demonstrate age-related and disease-related increases in rates of mutation in some but not all tissues. The further involvement of mitochondrial dysfunction in ageing is suggested by data on oxidative free radical production in mitochondria of birds versus rodents. These elegant studies indicate greatly reduced rates of free radical production in mitochondria of long-lived birds versus short-lived rodents. They further demonstrate that Complex I of the respiratory chain may be a major factor in these species-specific effects. Restriction of caloric intake (dietary restriction, DR) is the only manipulation known to consistently extend lifespan in a wide variety of species. Previous work shows that extension of lifespan in DR is not necessarily related to reduced metabolic rate per unit metabolic mass. More recent work in exercising DR rats demonstrates consistently high daily metabolic rates together with extended lifespan. Other studies also show altered characteristics of fuel use in DR, indicating the ability of DR rats to maintain appropriate rates of fuel use under conditions less damaging to the organism. All of these new approaches to the interaction of nutrition, energy expenditure and ageing suggest that regulation of energy balance and the characteristics of fuel use play significant roles in ageing and in age-related disease.