CR= calorie restriction
BMR= basal metabolic rate
PI=peroxidation index
MLSP=maximum lifespan potential
These are several quotes from an article I found interesting, along with some comments
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.
Laganiere and Yu (188) first showed CR altered the fatty acid composition of liver mitochondrial and microsomal membranes in rats such that they became less susceptible to peroxidative damage. Since this seminal observation, others have reported similar CR-induced changes for other tissues (53, 190, 201, 268, 270, 346) as well as for different classes of liver phospholipids (54, 168). All of these studies involved long-term CR in rats with the shortest period examined being 10-wk CR (54). A study of CR in mice (99) reports similar changes in the fatty acid composition of phospholipids from liver, heart, kidney, and brain, as well as liver and muscle mitochondria, with the changes in this study being manifest following 1 mo of CR (the earliest period sampled).
Naked mole rats are mouse sized and are the longest living rodents known, with a recorded MLSP exceeding 28 yr (44). Naked mole rats have a low BMR for their size (255), but the 30% reduction in BMR is not great enough to explain their fivefold extended maximum longevity. In a series of recent studies, several variables that are considered key tenets of the oxidative stress theory of aging have been compared between naked mole rats and similar-sized mice. Surprisingly, a large amount of the data obtained to date provide little support for a diminished level of oxidative damage in these long-living rodents. Although naked mole rats have low BMR, rates of hydrogen peroxide production are similar in heart mitochondria from both species (190a) and in vascular endothelial cells (187); no differences in overall antioxidant activities are evident (3), and levels of accrued oxidative damage to proteins, DNA, and lipids are greater in the longer-living species...
When membrane fatty acid composition was measured in tissues from naked mole rats, they were found to have very low levels of DHA in their tissue phospholipids for their body size. Although both mice and naked mole rats have similar levels of total unsaturated fatty acids in their tissue phospholipids, the low DHA levels in naked mole rats result in more peroxidation-resistant membranes. The PI values calculated for both skeletal muscle and liver mitochondria show that the peroxidation susceptibility of the membranes of naked mole rats is what one would predict for such a long-living rodent species
Humans also have low PI values, and iirc so do bats and long lived birds, the article elaborates more on this.
With regards to antioxidants, the article elaborates more(linked at the bottom), but in general it seems to suggest antioxidant defenses are at an adequate optimal level(though higher levels can protect from toxins, stresses, etc)
While maximum life span has been decreased in a number of studies following the complete removal of particular antioxidant defense (e.g., in homozygous knockouts), the overexpression of antioxidant defenses has essentially had no effect on maximum longevity. It is of interest that heterozygous knockouts (i.e., resulting in a 50% reduction in antioxidant levels) have often had no influence on maximum life span.
It seems the membrane composition can influence far longer lasting and likely more harmful byproducts...
The hydroperoxides and endoperoxides, generated by lipid peroxidation, can undergo fragmentation to produce a broad range of reactive intermediates, such as alkanals, alkenals, hydroxyalkenals, glyoxal, and malondialdehyde (MDA; Ref. 95) (see Fig. 2). These carbonyl compounds (collectively described as "propagators" in Fig. 2) have unique properties contrasted with free radicals. For instance, compared with ROS or RNS, reactive aldehydes have a much longer half-life (i.e., minutes instead of the microseconds-nanoseconds characteristic of most free radicals). Furthermore, the noncharged structure of aldehydes allows them to migrate with relative ease through hydrophobic membranes and hydrophilic cytosolic media, thereby extending the migration distance far from the production site. On the basis of these features alone, these carbonyl compounds can be more destructive than free radicals and may have far-reaching damaging effects on target sites both within and outside membranes.
The social insects have been suggested as particularly good model organisms to investigate the mechanisms of aging for two reasons: 1) "queens" can be extraordinarily long living, and 2) there is sometimes tremendous variation in life span between genetically identical "queens" and "workers" (171). In some ant species, queens can live up to 30 yr and frequently live 10 times longer than workers (144). Similarly, queen honeybees are reported to have a maximum longevity an order of magnitude greater than worker (i.e., nonreproductive female) honeybees (373). Enhanced antioxidant defenses in queens are not a likely explanation, as one study has shown queen ants have a reduced expression of Cu/Zn-SOD compared with shorter-living workers (282) while others have shown that queen honeybees generally have the same (or, in some cases, lower) levels of antioxidant defenses than worker honeybees (68, 370). The mass-specific metabolic rates of worker and queen honeybees are essentially the same (96). Recent measurements show that queen and worker honeybees have different membrane fatty acid composition and that the peroxidation index of phospholipids of from queen honeybees is 33% of that of workers (122). If the slope of the relationship between PI and MLSP is mathematically similar in honeybees to that described for mammals and birds (155, see Fig. 7), then this difference is capable of explaining the order of magnitude difference in longevity between queen and worker bees.
This is very interesting stuff, social insects can vary in lifespan in some cases by up two orders of magnitude despite being the same organisms from the same species with the same genome. An analysis of queens vs workers is in order, if we find that the main difference is membrane lipid composition even in cases of 100x lifespan increase, experimental intervention in mammals would be a must to see what kind of results can be obtained.
Some of these queens are hypothesized to exhibit negligible senescence, the naked mole rat appears to exhibit temporary negligible senescence for most of its lifespan, and it is also said that some birds appear to exhibit such in several tissues.
The details have to be investigated, but a cross species factor and intra species factor being found to have such a strong variation and correlation with lifespan is very intriguing.
Might it be that sufficiently lowering the production of these toxic substances with minute long half lifes, might be enough to allow existing maintenance mechanisms to exceed metabolic wear providing negligible senescence? After all if this turns out to be the primary intervention that provides two orders of magnitude increase in lifespan in some species, it would be extremely suggestive of being an extremely potent intervention in the aging process.
Rather, we suggest that the rate-of-living theory cannot alone explain all of the variation in longevity of animals. However, many of the exceptions that cannot be explained by the rate-of-living theory (and are summarized in sect. I) do appear capable of explanation by knowledge of membrane fatty acid composition in each particular case.
When the fact that fatty acids differ dramatically in their susceptibility to peroxidative damage is combined with species variation in membrane composition, the link between body size, metabolic rate, and longevity becomes more apparent.
In this contribution, we have discussed evidence that the fatty acid composition of membranes can potentially explain 1) the shorter longevity of small mammals compared with larger mammals, 2) the exceptional longevity of naked mole-rats compared with similar-sized mice, 3) the extended longevity of wild-derived lines of mice compared with laboratory mice, 4) the longer life spans of birds compared with similar-sized mammals, 5) the extended longevity of rodents caused by calorie restriction, 6) the longevity difference between workers and queens in honeybees, and 7) also suggested it may be an explanation for the exceptional longevity of our own species, Homo sapiens. Furthermore, we have also discussed the studies which show that membranes with fatty acid compositions prone to peroxidation are also associated with greater levels of lipoxidative damage to other cellular constituents. All these studies suggest that variation in membrane fatty acid composition may be an important missing piece of the jigsaw puzzle explaining aging and the mechanisms that determine the maximum life span specific for each species. It is a testable hypothesis that awaits further experiments.
Quote source link
Edited by steampoweredgod, 12 December 2011 - 09:00 PM.