Phospholipid composition and longevity: lessons from Ames dwarf mice

Abstract

Membrane fatty acid (FA) composition is correlated with longevity in mammals. The "membrane pacemaker hypothesis of ageing" proposes that animals which cellular membranes contain high amounts of polyunsaturated FAs (PUFAs) have shorter life spans because their membranes are more susceptible to peroxidation and further oxidative damage. It remains to be shown, however, that long-lived phenotypes such as the Ames dwarf mouse have membranes containing fewer PUFAs and thus being less prone to peroxidation, as would be predicted from the membrane pacemaker hypothesis of ageing. Here, we show that across four different tissues, i.e., muscle, heart, liver and brain as well as in liver mitochondria, Ames dwarf mice possess membrane phospholipids containing between 30 and 60 % PUFAs (depending on the tissue), which is similar to PUFA contents of their normal-sized, short-lived siblings. However, we found that that Ames dwarf mice membrane phospholipids were significantly poorer in n-3 PUFAs. While lack of a difference in PUFA contents is contradicting the membrane pacemaker hypothesis, the lower n-3 PUFAs content in the long-lived mice provides some support for the membrane pacemaker hypothesis of ageing, as n-3 PUFAs comprise those FAs being blamed most for causing oxidative damage. By comparing tissue composition between 1-, 2- and 6-month-old mice in both phenotypes, we found that membranes differed both in quantity of PUFAs and in the prevalence of certain PUFAs. In sum, membrane composition in the Ames dwarf mouse supports the concept that tissue FA composition is related to longevity.

Fig. 1

Heart phospholipid docosahexaenoic acid (DHA) content (a) and linoleic acid content (b) in 1-, 2- and 6-month-old Ames dwarf mice and normal-sized littermates. Total n _{Ames dwarf mice} = 18, total n _{normal littermates} = 21; means ± SEM

Fig. 2

Skeletal muscle phospholipid docosahexanenoic acid (DHA) content (a) and linoleic acid content (b) in 1-, 2- and 6-month-old Ames dwarf mice and normal-sized littermates. Total n _{Ames dwarf mice} = 18, total n _{normal littermates} = 21; means ± SEM

Fig. 3

Liver phospholipid docosahexanenoic acid (DHA) content (a) and linoleic acid content (b) in 1-, 2- and 6-month-old Ames dwarf mice and normal-sized littermates. Total n _{Ames dwarf mice} = 18, total n _{normal littermates} = 21; means ± SEM

Fig. 4

Brain phospholipid docosahexanenoic acid (DHA) content (a) and linoleic acid content (b) in 1-, 2- and 6-month-old Ames dwarf mice and normal-sized littermates. Total n _{Ames dwarf mice} = 18, total n _{normal littermates} = 21; means ± SEM

Fig. 5

Relationship and prediction intervals between maximum lifespan (MLSP) and muscle phospholipid PUFA content (top panel) and n-3 PUFA content (bottom panel) of five different strains of laboratory mice. Data obtained in this study are from Ames dwarf mouse tissues and controls, and all other data points from Hulbert et al. (2006a, b). AD control refers to heterozygous control Ames dwarf mice