Life and Death: Metabolic Rate, Membrane Composition, and Life Span of Animals

Abstract

Maximum life span differences among animal species exceed life span variation achieved by experimental manipulation by orders of magnitude. The differences in the characteristic maximum life span of species was initially proposed to be due to variation in mass-specific rate of metabolism. This is called the rate-of-living theory of aging and lies at the base of the oxidative-stress theory of aging, currently the most generally accepted explanation of aging. However, the rate-of-living theory of aging while helpful is not completely adequate in explaining the maximum life span. Recently, it has been discovered that the fatty acid composition of cell membranes varies systematically between species, and this underlies the variation in their metabolic rate. When combined with the fact that 1) the products of lipid peroxidation are powerful reactive molecular species, and 2) that fatty acids differ dramatically in their susceptibility to peroxidation, membrane fatty acid composition provides a mechanistic explanation of the variation in maximum life span among animal species. When the connection between metabolic rate and life span was first proposed a century ago, it was not known that membrane composition varies between species. Many of the exceptions to the rate-of-living theory appear explicable when the particular membrane fatty acid composition is considered for each case. Here we review the links between metabolic rate and maximum life span of mammals and birds as well as the linking role of membrane fatty acid composition in determining the maximum life span. The more limited information for ectothermic animals and treatments that extend life span (e.g., caloric restriction) are also reviewed.

Explaining longevity of different animals: is membrane fatty acid composition the missing link?

“…Furthermore, membrane composition was correlated with maximum lifespan in mammals (Pamplona et al 1998). These findings led to a modification of the oxidative stress theory of aging: the membranepacemaker theory (Hulbert 2005;Hulbert et al 2007). There are three basic reasons why membrane fatty acid composition can be argued to be an important factor in determining longevity: (1) membrane fatty acid composition varies systematically among species; (2) fatty acids differ dramatically in their susceptibility to peroxidation; and (3) many of the products of lipid peroxidation are themselves powerful reactive oxygen molecules (schematic provided in Fig.…”

“…Consequently, fatty acid Fig. 1 The relationship between basal metabolic rate and maximum life span of birds and mammals (modified from Hulbert et al 2007) chains with no double bonds (i.e. saturates; SFA), or those with only a single double bond (i.e.…”

“…The more polyunsaturated the PUFA, the more susceptible it is to peroxidation (Halliwell and Gutteridge 1999). By combining the susceptibilities of individual fatty acid chains with the measured percent fatty acid composition of membrane lipids, it is possible to calculate a "peroxidation index" (PI) for the particular membrane (see Hulbert et al 2007 for details). This single number gives an approximate indication of the susceptibility of a membrane to lipid peroxidation.…”

Energetics and longevity in birds

“…Two candidate ideas are the membrane pacemaker hypothesis, and the uncoupling to survive hypothesis. The membrane pacemaker hypothesis suggests that interspecific variation in metabolism can be traced to differences in the fatty acid desaturation of membranes (Brand et al 2002;Brookes et al 1998;Hulbert 2007;Hulbert andElse 1999, 2005;Hulbert et al 2002Hulbert et al , 2007Porter et al 1996). High levels of polyunsaturated fatty acids (PUFAs) are suggested to be linked to higher rates of mass-specific metabolism.…”

Wild-derived mouse stocks: an underappreciated tool for aging research

“…At present the mechanistic bases for these differences remain unknown, but telomere biology may be an important mediator of cellular stress resistance (Rubio et al 2004) and inbreeding has been shown to significantly alter telomere length in rodents (Hemann and Greider 2000;Manning et al 2002). In addition, significant differences in membrane fatty acid composition between wild-derived and laboratory mouse stocks (Hulbert et al 2006) may mediate the susceptibility of cellular membranes to peroxidation (Hulbert et al 2007), although there are no differences in free radical production by isolated heart mitochondria in wildderived versus laboratory mice (Lambert et al 2007). …”