Abstract

Underlying causes of species differences in maximum life span (MLS) are unknown, although differential vulnerability of membrane phospholipids to peroxidation is implicated. Membrane composition and longevity correlate with body size; membranes of longer-living, larger mammals have less polyunsaturated fatty acid (PUFA). We determined membrane phospholipid composition of naked mole-rats (MLS > 28.3 years) and similar-sized mice (MLS = 3–4 years) by gas–liquid chromatography to assess if the ∼9× MLS difference could be explained. Mole-rat membrane composition was unchanged with age. Both species had similar amounts of membrane total unsaturated fatty acids; however, mice had 9 times more docosahexaenoic acid (DHA). Because this n-3PUFA is most susceptible to lipid peroxidation, mole-rat membranes are substantially more resistant to oxidative stress than are mice membranes. Naked mole-rat peroxidation indices, calculated from muscle and liver mitochondrial membranes, concur with those predicted by MLS rather than by body size, suggesting that membrane phospholipid composition is an important determinant of longevity.

Considerable insights into the mechanisms of aging and the physiological basis for longevity are likely to emerge from studies exploiting the wide variation in maximum life span (MLS) seen in similar-sized species, especially if these studies primarily focus on comparative differences between species that show disparate longevity. Naked mole-rats (Heterocephalus glaber) are small mammals that exhibit exceptional longevity. This mouse-sized rodent (∼35 g) has a captive MLS of >28.3 years (1) which is the longest MLS known for any rodent species and is 8–9 times greater than the 3–4 year MLS reported for similar-sized Mus musculus (2). Naked mole-rats not only exhibit extraordinary life spans, but these subterranean Northeast African rodents also show attenuated age-related declines in physiological function and body composition (3), and continue to breed well into their third decade of life (2). Based on the allometric equations of Prothero and Jurgens (4), naked mole-rats have a longevity quotient (the ratio of actual MLS to that predicted from body mass) of ∼10, which is the same as that reported for humans, another very long-living mammal species (4). The naked mole-rat may therefore be an excellent new animal model with which to assess mechanisms that influence longevity and the aging process.

The “oxidative stress” theory is currently the most widely accepted explanation of how aging occurs. It proposes that reactive oxygen species (ROS) produced as a by-product of normal aerobic metabolism continuously damage cellular nucleic acids, proteins, and membrane lipids (5). Fatty acids vary considerably in their susceptibility to ROS attack, and their vulnerability to peroxidation is primarily dependent on the number of double bonds within the acyl chain (6). The most highly polyunsaturated n-3 fatty acids (PUFA) are the most at risk of peroxidative damage, whereas n-6 PUFA are generally less vulnerable, and saturated (SFA) and monounsaturated fatty acids (MUFA) are extremely resistant to ROS attack. Many of the products of lipid peroxidation are themselves very potent ROS that can induce considerable damage to other biological molecules (7). Consequently, lipid peroxidation is an autocatalytic self-propagating process that, after exceeding the capacity of antioxidant defenses, will do great damage. Indeed, two aldehydes produced from lipid peroxidation, namely, hydroxynonenal and hydroxyhexenal, are important secondary radicals and are considered to be responsible for much of the cellular damage associated with oxidative stress (7).

The “membrane pacemaker” theory of aging (8) is a recent extension of the “oxidative stress” theory of aging. This theory is based on studies that highlight the disparate risk of various membrane fatty acids to oxidative damage (6) and the correlation thereof with longevity (9–13), and predicts that membrane phospholipid composition may be an important determinant of aging and life span. The proportion of highly polyunsaturated fatty acids in membrane phospholipids appears to correlate positively with metabolism (14) and inversely with both body size (15) and maximum longevity (8,13,16–18). The longer MLS of large mammal species compared to that of small mammals is associated with cell membranes considered peroxidation-resistant because of their lower proportion of PUFAs and in particular n-3 PUFAs (8,15,17). In the same way, the long life span of birds compared to similar-sized mammals is associated with peroxidation-resistant membranes (9,19). Indeed, in most vertebrates, membrane fatty acid composition varies in a predictable way with both body size (15) and MLS (8,13). The current study was undertaken to test whether the exceptionally long-living mouse-sized naked mole-rat has a membrane composition commensurate with its body size (i.e., peroxidation prone) or if it has peroxidation-resistant membranes, more in keeping with its MLS. We specifically chose to include a wide range of ages and tissue types to assess whether: (a) membrane composition is an age-dependent trait; (b) species differences are manifest across all tissues; and (c) fatty acid composition of membrane phospholipids may predict MLS potential (MLSP) of an exceptionally long-living small mammal.

Materials and Methods

Animals

Naked mole-rats of three different age groups (0.25 years, 2 years, 22 years) were obtained from a captive colony maintained in the Department of Biology, City College of New York. Animals were housed under simulated burrow conditions (30°C, 75% relative humidity) and were fed a diet of fresh fruit and vegetables supplemented with a protein-rich moist cereal (Pronutro; Bokomo Foods, Cape Town, South Africa). No free water was supplied. Mice (CB57BL6, 0.25 years, 20.2 g) were purchased from Charles River Laboratories (Wilmington, MA) and were housed under standard rodent conditions.

Tissue Collection

All animals were killed by cardiac exsanguinations following anesthesia (sodium pentobarbital 60 mg/kg). Tissues were rapidly harvested and flash frozen in liquid nitrogen prior to storage at –80°C. Mitochondria were prepared from a portion of fresh liver by methods described previously (19), immediately following the killing of the animal. Tissue and mitochondria samples were kept frozen at –80°C until extraction of lipids (<2 weeks).

Phospholipid Extraction

Total lipids were extracted from tissues by using ultrapure grade chloroform/methanol (2:1, vol/vol) containing butylated hydroxytoluene (0.01% wt/vol) as an antioxidant. Total lipid extracts were dried and sealed under a nitrogen atmosphere in small vials. Phospholipids were separated from neutral lipids by solid-phase extraction on silica Sep-Pak columns (Waters, Milford, MA). Phospholipids were transmethylated, and fatty acid methyl esters were separated by gas–liquid chromatography on a Shimadzu GC-17A gas chromatograph (Shimadzu Corp., Kyoto, Japan) with a fused silica capillary column [as described in (15,19)]. Individual fatty acids were identified by comparing each peak's retention time to those of external standards, and then were expressed as the mol % of total fatty acids.

Peroxidation Index

Peroxidation index (PI) is calculated as PI = (0.025 × % monoenoics) + (1 × % dienoics) + (2 × % trienoics) + (4 × % tetraenoics) + (6 × % pentaenoics) + (8 × % hexaenoics).

Statistical Analyses

Significant differences between tissues, age groups, and species were determined by analyses of variance conducted using the JMP v5.1 statistical package (SAS Institute Inc., Cary, NC). Where analysis of variance revealed a significant effect, Tukey's post hoc test was used to identify individual significant differences. Data were considered significantly different at p <.05. Values in text and tables are expressed as mean ± standard error of the mean.

Results

Figure 1 presents the fatty acid composition of tissue phospholipids from juvenile (0.25 years), young adult (2 year), and old adult (22 years) naked mole-rats compared to young adult (0.25 years) laboratory mice. The actual fatty acid data for both species samples from all tissues and age groups are shown in the Appendix as Supplemental Tables 1–6.

Membrane Composition and Tissue Type

The pattern of phospholipid fatty acid composition of mice tissues was as reported previously. With the exception of brain tissue, membrane composition showed only small differences among tissues within a species (Tables 1 and 2; Figure 1) Brain phospholipids had the lowest percentage of PUFAs; however, considerably more MUFA was present within this tissue. The same suite of comparative phospholipid differences is also evident in mitochondria. Liver mitochondria from adult naked mole-rats and adult mice have phospholipids with the same composition and PI as that measured for liver total phospholipids (see Figure 1, bottom graphs).

Membrane Composition and Age of Naked Mole-Rat

In general, membrane phospholipid composition of naked mole-rat tissues was constant between 0.25 years and 22 years of age (see Figure 1). For some tissues, there were small differences between juvenile and adult naked mole-rats. Skeletal muscle and heart phospholipids (and to a lesser extent kidney phospholipids) showed an increase in n-6 PUFA and a decrease in MUFA content between 0.25-year-old and 2-year-old animals. Brain phospholipids were essentially unchanged between different age groups, whereas liver phospholipids showed a small decrease in n-3 PUFA and a small increase in n-6 PUFA between 0.25-year-old and 2-year-old naked mole-rats. Membrane composition does not appear to change significantly with age and rather is a relatively constant species characteristic.

Species Differences in Membrane Composition

Tissue phospholipids from naked mole-rats have the same percentage of total unsaturated fatty acids as do those from mice (Figure 1); these percentages are equal to those predicted for the naked mole-rat body size (15,20) (see Figure 2). However, the proportions of different types of unsaturated fatty acids present in their membrane bilayers are unlike those of mice and dissimilar to those predicted by body size (Tables 1 and 2). The most pronounced interspecies difference is the dramatically reduced abundance of the highly polyunsaturated docosahexaenoic acid (DHA or 22:6 n-3) in phospholipids of naked mole-rats. Phospholipids from skeletal muscle, heart, kidney, and liver of naked mole-rats contained an average 2.2% DHA (range 0.6%–6.5%) and were 1/9 that observed in the same tissues from mice (average 19.3%; range 11.7%–26.2%). Brain phospholipids had the highest DHA content of all tissues in naked mole-rats (∼12%), but even this was significantly lower than the 15.6% measured in mice brain phospholipids.

Discussion

Our data show that membrane composition does not vary greatly with age within naked mole-rats, but rather is a species-specific trait that correlates better with MLS than with body size. Indeed, pronounced differences in the proportion of n-3 and n-6 PUFAs are evident among the two similar-sized species that show disparate longevity. The data for mice (CB57BL6 strain) are essentially the same as those previously reported for other laboratory strains of Mus musculus (15,18,20); however, these data are markedly different from those of similar-sized longer-living naked mole-rats. Previous studies of tissue phospholipid composition of mammals, varying in size from shrews to cattle, allow us to predict what we would expect for tissues from a 36.5 g mammal (15,20). The values we report here for young adult (2-year-old) naked mole-rats are compared to such predictions in Figure 2. Phospholipids from all tissues have approximately the predicted content of total unsaturated fatty acids (% UFA), but a much lower-than-predicted % n-3 PUFA content which is compensated for by either a higher-than-predicted % MUFA or higher-than-predicted % n-6 PUFA depending on the tissue. The lower-than-predicted n-3 PUFA content in tissue phospholipids from naked mole-rats is overwhelmingly due to a low DHA content. Indeed, comparative differences in DHA content between mice and naked mole-rats (that mice have 9 times more DHA) correspond well, albeit inversely, with the 8- to 9-fold observed difference in longevity. These data collectively show that, for their body size, naked mole-rats have membrane bilayers that are very low in peroxidation-prone fatty acids and have proportionately more peroxidation-resistant fatty acids (Figure 2).

DHA (22:6 n-3) is the fatty acid most susceptible to peroxidation, being 320 times more prone to peroxidation than is the monounsaturated oleic acid (18:1 n-9) and 8 times more susceptible than is the n-6 linoleic acid (18:2 n-6) (6,8). Combining the relative susceptibilities of individual fatty acids with the fatty acid composition, it is possible to calculate a PI which is an overall measure of the susceptibility of membrane phospholipids to lipid peroxidation (see Materials and Methods). Although the phospholipids of naked mole-rats and mice have essentially the same percentage of unsaturated fatty acids, the very different composition within PUFAs between these two species results in a lower PI for tissue phospholipids from naked mole-rats compared to mice (see right-hand graphs in Figure 1). The only tissue for which this is not statistically significant is the brain. Brain phospholipids from mice have the lowest PI of all mouse tissues, and the brain membranes of the naked mole-rat have a PI similar to that calculated for mice. Conserved fatty acid composition in mammalian brains has been previously reported (15,18), and high levels of n-3 PUFAs may reflect the high metabolic demands of the brain and the critical need to maintain membrane fluidity and intracellular signalling processes (21). The lower PI (relative to that observed in mouse tissue) indicates that membranes of skeletal muscle, heart, kidney, and liver of naked mole-rats are significantly more resistant to lipid peroxidation than are the respective membranes in mice, and indeed naked mole-rats have similar values to those previously observed in much larger, yet exceptionally long-living, humans.

In all tissues, the contribution of n-3 PUFA to total PUFA was significantly lower in naked mole-rats compared to mice. In other words, the low DHA content of naked mole-rat membranes is offset by a relatively higher n-6 PUFA content compared to mice. The n-6 PUFA are generally less susceptible to peroxidation than are n-3 PUFA. This compensatory difference in n-3 PUFA and n-6 PUFA was most pronounced in skeletal muscle, heart, and brain phospholipids. In kidney and liver phospholipids, the low n-3 PUFA content in naked mole-rats was countered primarily by a greater content of monounsaturated fatty acids. We currently do not know the exact contribution of diet to these differences in PUFA composition. Naked mole-rats consume a variety of mixed fruits and vegetables supplemented with a high protein cereal that is rich in both linolenic and linoleic acids; rodent chow also has similar proportions of these two important fatty acids. Although diet may contribute slightly to the observed differences, we believe that the very pronounced tissue differences reflect species-specific traits.

To date, the relationship between PI and MLSP has been determined only for skeletal muscle and liver mitochondrial phospholipids (8). The relationship between PI of skeletal muscle phospholipids from 11 mammal and 9 bird species and their MLSP has been described by the equation PI = 397.MLSP−0.33, whereas that for liver mitochondrial phospholipids from 9 mammal and 8 bird species is PI = 475.MLSP−0.40 (see Figure 3). Measured values for naked mole-rats agree with the relationships described above. From these relationships, by knowing the membrane phospholipids PI we can predict an MLSP for a species. The PI of skeletal muscle phospholipids from 0.25-year-old, 2-year-old, and 22-year-old naked mole-rats predict an MLSP of 37 years, 19 years, and 20 years, respectively. The expected liver mitochondrial phospholipids PI for an animal with a 28-year MLSP is 125, whereas the observed value (PI = 139) predicts an MLSP of 21 years for naked mole-rats. These predicted MLSPs (predicted from measured PI values) are considerably closer to the actual MLSP of ∼28 years recorded for naked mole-rats than the ∼4 years predicted from their body mass (3). The tissues of naked mole-rats thus have membranes that are peroxidation-resistant compared to the tissues of similarly sized mammals (such as mice), and have the same degree of peroxidation resistance as do tissues of mammals and birds with similar longevity.

The shift in the balance of PUFA in cellular membranes of naked mole-rats, from the peroxidation-prone n-3 PUFA (especially DHA) to the more peroxidation-resistant n-6 PUFA, is a similar shift to that seen in birds which are longer living than mammals of the same size (8). For example, pigeons and rats are similar in both body mass and metabolic rate, yet pigeons have an MLSP of ∼35 years compared to 3–4 years for rats. The n-3/n-6 ratio for skeletal muscle phospholipids from rats is 0.36, whereas from pigeons it is 0.18 [data from (18,20)] and from naked mole-rats it is 0.15. Similarly, the value of the ratio for liver mitochondrial membranes is 0.46 for rats, compared to 0.22 for pigeons [data from (9,19,22)] and 0.18 for naked mole-rats. Indeed, the relative proportions of these polyunsaturated fatty acids are responsible for the low membrane PI, and thus likely contribute significantly to the extended longevity of naked mole-rats.

Naked mole-rats do not appear to have antioxidant defenses superior to those of mice, thus antioxidant defenses are not likely responsible for the 8- to 9-fold difference in longevity between these species (23). Similarly, antioxidant enzyme activities in both pigeons and rats do not reflect the 9-fold difference in their longevity (24). Surprisingly, even at an early age (7% of MLSP), naked mole-rats appear to have higher levels of oxidative damage to lipids, proteins, and DNA than mice have (25). A substantial interspecies difference in urinary isoprostane excretion has been observed. This difference may be related to the higher levels of n-6 PUFA in tissue (especially muscle) phospholipids of naked mole-rats compared to mice, for isoprostanes are derived from the lipid peroxidation of n-6 PUFA (7). To date, we cannot explain why this long-living rodent accrues significant levels of oxidative damage, even a very early age (25). One of us (RB) has speculated that this may be a laboratory-induced artefact related to housing newly born animals under comparatively hyperoxic conditions relative to those found in their natural habitat of underground sealed burrow systems (2). After early-age oxidative damage accrual, the amount of oxidative damage to lipids, proteins, and DNA observed in various tissues remains relatively constant, suggesting that age-related rates of damage accrual decline. Naked mole-rats appear to be far more tolerant of this early-onset damage that do mice and appear able to live and thrive for many years with these levels of tissue damage (2).

Summary

Fatty acid composition of naked mole-rat membranes from a variety of tissues correlates better with their MLSP than with their body size. This finding suggests that the presence of relatively peroxidation-resistant cellular membranes can explain the exceptional longevity of naked mole-rats. Similarly, this may also be the explanation for the relatively long MLSP of Homo sapiens. We have recently observed that the extended longevity of wild-derived strains of mice relative to laboratory mice is also associated with low PI in muscle and liver phospholipids (26). Furthermore, in this respect, a senescence-prone substrain of senescence-accelerated mice have brain mitochondrial membranes with a significantly elevated PI compared to those from a senescence-resistant substrain of these mice (27). This finding suggests that the relationship between membrane composition and longevity holds true for both intra- and interspecies comparisons. We cannot ascertain from these results, however, whether this relationship is one of “cause and effect.” Only experimental manipulation of membrane fatty acid composition that alters both PI and maximum longevity can prove a causal relationship. Such an experiment is difficult in the naturally long-living naked mole-rat, but it is of interest that the life-span–extending experimental treatment of calorie restriction results in mitochondrial membrane fatty acid changes that increase peroxidation-resistance in rats (28). Similarly, calorie restriction can significantly reduce the PI of membrane phospholipids within 1 month in mice (29). It is not known whether dietary changes in PUFA content alter membrane fatty acid composition with concomitant effects on susceptibility to oxidative damage. However, our data collectively reveal that composition of membrane bilayers may be an important determinant of MLS.

Appendix

Supplemental Tables 1–6:Actual Fatty Acid Data for Both Species Samples From All Tissues and Age Groups Are Shown

Decision Editor: Huber R. Warner, PhD

Figure 1.

Phospholipid fatty acid composition of tissues and liver mitochondria from adult mice (0.25 years) and juvenile (0.25 years), young adult (2 years) and old adult (22 years) naked mole-rats. Each segment of the pie chart represents the following fatty acids (clockwise order): saturates (light hatch: 16:0, 18:0), monounsaturates (stippled: 16:1, 18:1n-9, 18:1n-7), n-6 polyunsaturates (white: 18:2, 20:4, 22:4, 22:5), n-3 polyunsaturates (grey: 18:3, 22:5, black: 22:6). Irrespective of age, naked mole-rat membrane lipids have a very low content of the peroxidation-prone docosahexaenoic acid (22:6, black sector of pie chart). Right-hand column graphs: Regardless of age, the calculated peroxidation index (PI) of mole-rat membrane lipids is lower than that for mice, indicative of peroxidation-resistant membranes. Error bars are ± 1 standard error of the mean. *Significantly different from mice

Figure 1.

Phospholipid fatty acid composition of tissues and liver mitochondria from adult mice (0.25 years) and juvenile (0.25 years), young adult (2 years) and old adult (22 years) naked mole-rats. Each segment of the pie chart represents the following fatty acids (clockwise order): saturates (light hatch: 16:0, 18:0), monounsaturates (stippled: 16:1, 18:1n-9, 18:1n-7), n-6 polyunsaturates (white: 18:2, 20:4, 22:4, 22:5), n-3 polyunsaturates (grey: 18:3, 22:5, black: 22:6). Irrespective of age, naked mole-rat membrane lipids have a very low content of the peroxidation-prone docosahexaenoic acid (22:6, black sector of pie chart). Right-hand column graphs: Regardless of age, the calculated peroxidation index (PI) of mole-rat membrane lipids is lower than that for mice, indicative of peroxidation-resistant membranes. Error bars are ± 1 standard error of the mean. *Significantly different from mice

Figure 2.

Composition of tissue phospholipids from young adult (2 year) naked mole-rats compared to that predicted for a mammal of the same body size (36.5 g). The predictions for tissue total phospholipids are from equations obtained from (15), whereas those for liver mitochondrial phospholipids are from the equations of (20). Hatched area: 90%–110% of predicted values. UFA = unsaturated fatty acids; MUFA = monounsaturates; PUFA = polyunsaturates; 22:6 n-3 = docosahexaenoic acid. For their body size, naked mole-rat membrane lipids have the expected percent total unsaturated fatty acids, but exhibit reduced n-3 PUFA, especially reduced 22:6 n-3 content. In skeletal muscle and heart, the low n-3 PUFA is compensated by a greater amount of the more peroxidation-resistant n-6 PUFA, whereas in the other tissues the low n-3 PUFA is compensated for by high levels of the very peroxidation-resistant MUFA

Figure 2.

Composition of tissue phospholipids from young adult (2 year) naked mole-rats compared to that predicted for a mammal of the same body size (36.5 g). The predictions for tissue total phospholipids are from equations obtained from (15), whereas those for liver mitochondrial phospholipids are from the equations of (20). Hatched area: 90%–110% of predicted values. UFA = unsaturated fatty acids; MUFA = monounsaturates; PUFA = polyunsaturates; 22:6 n-3 = docosahexaenoic acid. For their body size, naked mole-rat membrane lipids have the expected percent total unsaturated fatty acids, but exhibit reduced n-3 PUFA, especially reduced 22:6 n-3 content. In skeletal muscle and heart, the low n-3 PUFA is compensated by a greater amount of the more peroxidation-resistant n-6 PUFA, whereas in the other tissues the low n-3 PUFA is compensated for by high levels of the very peroxidation-resistant MUFA

Figure 3.

The relationships between maximum life span potential (MLSP) and the peroxidation index of (A) skeletal muscle phospholipids, and (B) liver mitochondrial phospholipids of mammal and bird species. The values for other mammal species and birds are taken from Hulbert (8) and are represented by open squares. Values for adult naked mole-rats are indicated by filled circles and are plotted with ± 1 standard error of the mean. The values for humans are also indicated. The peroxidation indices calculated for naked mole-rat membrane lipids are as expected for a long-living endotherm

Figure 3.

The relationships between maximum life span potential (MLSP) and the peroxidation index of (A) skeletal muscle phospholipids, and (B) liver mitochondrial phospholipids of mammal and bird species. The values for other mammal species and birds are taken from Hulbert (8) and are represented by open squares. Values for adult naked mole-rats are indicated by filled circles and are plotted with ± 1 standard error of the mean. The values for humans are also indicated. The peroxidation indices calculated for naked mole-rat membrane lipids are as expected for a long-living endotherm

Table 1.

Differences in Relative Proportion of Various Membrane Phospholipids in Different Tissues of Young Adult Naked Mole-Rats and Mice.

Membrane Phospholipid (%) Skeletal Muscle Heart Muscle Kidney Liver Brain 
% UFA      
    Mice 57.2 ± 0.4 61.5 ± 1.2 60.6 ± 0.8 57.1 ± 0.4 54.2 ± 0.5 
    Mole-rats 60.5 ± 0.4* 66.2 ± 1.5* 61.0 ± 0.8 56.0 ± 0.4 55.0 ± 1.5 
% MUFA      
    Mice 12.8 ± 0.6 12.5 ± 2.4 12.8 ± 1.3 11.5 ± 0.4 26.8 ± 0.8 
    Mole-rats 12.6 ± 0.3 16.7 ± 1.1* 22.0 ± 0.7* 15.4 ± 0.3* 25.7 ± 0.9 
% PUFA      
    Mice 44.3 ± 1.0 49.0 ± 3.5 47.8 ± 0.8 45.6 ± 0.2 27.4 ± 0.3 
    Mole-rats 47.9 ± 0.7* 49.5 ± 2.2 39.0 ± 0.9* 40.6 ± 0.3* 29.3 ± 1.0* 
% n-6      
    Mice 21.9 ± 0.2 21.1 ± 1.6 29.7 ± 0.7 32.2 ± 0.5 11.8 ± 0.2 
    Mole-rats 41.7 ± 1.0* 45.5 ± 2.3* 34.4 ± 0.9* 34.2 ± 0.5* 17.7 ± 0.7* 
% n-3      
    Mice 22.5 ± 0.6 28.0 ± 2.0 18.1 ± 1.1 13.4 ± 0.4 15.6 ± 0.2 
    Mole-rats 6.2 ± 0.5* 4.0 ± 0.3* 4.6 ± 0.2* 6.3 ± 0.4* 11.6 ± 0.3* 
Membrane Phospholipid (%) Skeletal Muscle Heart Muscle Kidney Liver Brain 
% UFA      
    Mice 57.2 ± 0.4 61.5 ± 1.2 60.6 ± 0.8 57.1 ± 0.4 54.2 ± 0.5 
    Mole-rats 60.5 ± 0.4* 66.2 ± 1.5* 61.0 ± 0.8 56.0 ± 0.4 55.0 ± 1.5 
% MUFA      
    Mice 12.8 ± 0.6 12.5 ± 2.4 12.8 ± 1.3 11.5 ± 0.4 26.8 ± 0.8 
    Mole-rats 12.6 ± 0.3 16.7 ± 1.1* 22.0 ± 0.7* 15.4 ± 0.3* 25.7 ± 0.9 
% PUFA      
    Mice 44.3 ± 1.0 49.0 ± 3.5 47.8 ± 0.8 45.6 ± 0.2 27.4 ± 0.3 
    Mole-rats 47.9 ± 0.7* 49.5 ± 2.2 39.0 ± 0.9* 40.6 ± 0.3* 29.3 ± 1.0* 
% n-6      
    Mice 21.9 ± 0.2 21.1 ± 1.6 29.7 ± 0.7 32.2 ± 0.5 11.8 ± 0.2 
    Mole-rats 41.7 ± 1.0* 45.5 ± 2.3* 34.4 ± 0.9* 34.2 ± 0.5* 17.7 ± 0.7* 
% n-3      
    Mice 22.5 ± 0.6 28.0 ± 2.0 18.1 ± 1.1 13.4 ± 0.4 15.6 ± 0.2 
    Mole-rats 6.2 ± 0.5* 4.0 ± 0.3* 4.6 ± 0.2* 6.3 ± 0.4* 11.6 ± 0.3* 

Notes: *p <.05.

UFA = unsaturated fatty acid; MUFA = monounsaturated fatty acid; PUFA = polyunsaturated fatty acid.

Table 2.

Fatty Acid Composition of Phospholipids in Skeletal Muscle, Liver, and Brain of Young Adult Naked Mole-Rats (NMR) and Mice.

 Muscle
 
 Liver
 
 Brain
 
  
Fatty Acid NMR Mice  NMR Mice  NMR Mice  
N SI SI SI 
16:00 18.4 ± 0.6 26.9 ± 0.4 HS 16.7 ± 0.5 24.1 ± 0.9 HS 26.3 ± 0.8 24.1 ± 0.3 NS 
16:1 n-7 0.9 ± 0.0 1.5 ± 0.0 HS 1.2 ± 0.2 1.0 ± 0.2 NS 1.3 ± 0.1 0.6 ± 00 HS 
18:00 19.6 ± 0.3 14.6 ± 0.3 HS 25.6 ± 0.6 18.0 ± 1.1 HS 16.8 ± 2.2 20.5 ± 0.3 NS 
18:1 n-9 7.5 ± 0.3 6.8 ± 0.4 HS 11.2 ± 0.4 8.0 ± 0.2 HS 17.6 ± 0.6 18.1 ± 0.2 
18:1 n-7 3.7 ± 0.1 3.8 ± 0.1 HS 2.4 ± 0.2 2.0 ± 0.1 HS 5.0 ± 0.2 4.4 ± 0.1 
18:2 n-6 19.3 ± 1.0 9.3 ± 0.4 HS 13.7 ± 0.7 14.8 ± 0.3 NS 0.7 ± 0.1 0.6 ± 0.0 NS 
18:3 n-3 0.5 ± 0.1 0.2 ± 0.0 HS 0.5 ± 0.1 0.2 ± 0.0 ND ND  
20:2 n-6 0.4 ± 0.1 0.4 ± 0.0 HS 1.4 ± 0.1 1.5 ± 0.1 NS ND ND  
20:3 n-6 0.9 ± 0.1 1.3 ± 0.3 NS 14.4 ± 0.4 15.3 ± 0.3 ND ND  
20:4 n-6 17.8 ± 0.5 9.6 ± 0.2 HS 0.4 ± 0.1 1.1 ± 0.1 HS 12.7 ± 0.5 8.6 ± 0.2 
22:4 n-6 1.7 ± 0.1 0.6 ± 0.0 HS 1.9 ± 0.2 0.1 ± 0.0 HS 2.8 ± 0.2 1.9 ± 0.0 HS 
22:5 n-6 1.3 ± 0.1 0.8 ± 0.0 2.1 ± 0.1 0.1 ± 0.0 HS 0.8 ± 0.1 0.1 ± 0.0 HS 
22:5 n-3 2.7 ± 0.3 2.6 ± 0.4 NS 2.3 ± 0.2 0.4 ± 0.0 HS ND ND  
22:6 n-3 2.2 ± 0.3 19.5 ± 0.5 HS 3.2 ± 0.4 11.7 ± 0.2 HS 11.1 ± 0.3 15.1 ± 0.2 HS 
 Muscle
 
 Liver
 
 Brain
 
  
Fatty Acid NMR Mice  NMR Mice  NMR Mice  
N SI SI SI 
16:00 18.4 ± 0.6 26.9 ± 0.4 HS 16.7 ± 0.5 24.1 ± 0.9 HS 26.3 ± 0.8 24.1 ± 0.3 NS 
16:1 n-7 0.9 ± 0.0 1.5 ± 0.0 HS 1.2 ± 0.2 1.0 ± 0.2 NS 1.3 ± 0.1 0.6 ± 00 HS 
18:00 19.6 ± 0.3 14.6 ± 0.3 HS 25.6 ± 0.6 18.0 ± 1.1 HS 16.8 ± 2.2 20.5 ± 0.3 NS 
18:1 n-9 7.5 ± 0.3 6.8 ± 0.4 HS 11.2 ± 0.4 8.0 ± 0.2 HS 17.6 ± 0.6 18.1 ± 0.2 
18:1 n-7 3.7 ± 0.1 3.8 ± 0.1 HS 2.4 ± 0.2 2.0 ± 0.1 HS 5.0 ± 0.2 4.4 ± 0.1 
18:2 n-6 19.3 ± 1.0 9.3 ± 0.4 HS 13.7 ± 0.7 14.8 ± 0.3 NS 0.7 ± 0.1 0.6 ± 0.0 NS 
18:3 n-3 0.5 ± 0.1 0.2 ± 0.0 HS 0.5 ± 0.1 0.2 ± 0.0 ND ND  
20:2 n-6 0.4 ± 0.1 0.4 ± 0.0 HS 1.4 ± 0.1 1.5 ± 0.1 NS ND ND  
20:3 n-6 0.9 ± 0.1 1.3 ± 0.3 NS 14.4 ± 0.4 15.3 ± 0.3 ND ND  
20:4 n-6 17.8 ± 0.5 9.6 ± 0.2 HS 0.4 ± 0.1 1.1 ± 0.1 HS 12.7 ± 0.5 8.6 ± 0.2 
22:4 n-6 1.7 ± 0.1 0.6 ± 0.0 HS 1.9 ± 0.2 0.1 ± 0.0 HS 2.8 ± 0.2 1.9 ± 0.0 HS 
22:5 n-6 1.3 ± 0.1 0.8 ± 0.0 2.1 ± 0.1 0.1 ± 0.0 HS 0.8 ± 0.1 0.1 ± 0.0 HS 
22:5 n-3 2.7 ± 0.3 2.6 ± 0.4 NS 2.3 ± 0.2 0.4 ± 0.0 HS ND ND  
22:6 n-3 2.2 ± 0.3 19.5 ± 0.5 HS 3.2 ± 0.4 11.7 ± 0.2 HS 11.1 ± 0.3 15.1 ± 0.2 HS 

Notes: Fatty acids are identified by the number of C atoms:number of double bonds and the position of the terminal bond. Values are mean ± standard error of the mean.

SI = Statistical significance; highly significant (HS) <.001; significant (S) <.05; not significant (NS) >.05.

ND, not detected.

Supplemental Table 1.Fatty Acid Composition of Skeletal Muscle Phospholipids From Juvenile (0.25 Years), Young Adult (2 Years), and Old Adult (22 Years) Naked Mole-Rats (NMR) and Young Adult (0.25 Years) Mice.

 Juvenile NMR Young Adult NMR Old Adult NMR Young Adult Mice Significance of Difference 
N 
16:0 16.3 ± 2.3a 18.4 ± 0.6b 20.1 ± 0.9a 26.9 ± 0.4b <.0001 
16:1 n-7 1.9 ± 0.3a 0.9 ± 0.0b 1.0 ± 0.2b 1.5 ± 0.0a <.0001 
18:0 20.5 ± 0.7a 19.6 ± 0.3a 15.8 ± 0.7b 14.6 ± 0.3b <.0001 
18:1 n-9 15.6 ± 1.1a 7.5 ± 0.3b 6.4 ± 0.8b 6.8 ± 0.4b <.0001 
18:1 n-7 4.6 ± 0.2a 3.7 ± 0.1b 5.3 ± 0.2c 3.8 ± 0.1b <.0001 
18:2 n-6 15.5 ± 1.5a 19.3 ± 1.0b 23.2 ± 1.2c 9.3 ± 0.4d <.0001 
18:3 n-3 1.3 ± 0.2a 0.5 ± 0.1b 0.5 ± 0.2b 0.2 ± 0.0b <.0001 
20:2 n-6 2.5 ± 0.6a 0.4 ± 0.1b 0.2 ± 0.1b 0.4 ± 0.0b <.0001 
20:3 n-6 1.2 ± 0.2 0.9 ± 0.1 0.6 ± 0.1 1.3 ± 0.3 NS 
20:4 n-6 9.5 ± 1.1a 17.8 ± 0.5b 18.0 ± 0.8b 9.6 ± 0.2a <.0001 
22:4 n-6 1.0 ± 0.3a 1.7 ± 0.1b 1.8 ± 0.2b 0.6 ± 0.0a <.0001 
22:5 n-6 0.8 ± 0.3a 1.3 ± 0.1b 1.1 ± 0.1ab 0.8 ± 0.0a .01 
22:5 n-3 2.0 ± 0.1 2.7 ± 0.3 2.5 ± 0.1 2.6 ± 0.4 NS 
22:6 n-3 2.2 ± 0.1a 2.2 ± 0.3a 1.8 ± 0.1a 19.5 ± 0.5b <.0001 
% UFA 61.3 ± 3.4a 60.5 ± 0.4a 63.1 ± 1.2b 57.2 ± 0.4a .02 
% MUFA 23.4 ± 1.1a 12.6 ± 0.3b 12.9 ± 1.1b 12.8 ± 0.6b <.0001 
% PUFA 38.0 ± 3.7a 47.9 ± 0.7b 50.1 ± 2.1b 44.3 ± 1.0b .0005 
% n-6 PUFA 30.9 ± 3.9a 41.7 ± 1.0b 45.0 ± 2.0b 21.9 ± 0.2c <.0001 
% n-3 PUFA 7.0 ± 0.5a 6.2 ± 0.5a 5.1 ± 0.2a 22.5 ± 0.6b <.0001 
% C20-22 21.3 ± 2.1a 28.1 ± 1.0b 26.5 ± 0.9b 35.2 ± 0.9c <.0001 
Ave. CL 18.1 ± 0.1a 18.3 ± 0.0b 18.2 ± 0.0ab 18.6 ± 0.0c <.0001 
PI 110.6 ± 7.9a 148.0 ± 4.6b 143.6 ± 4.6b 231.3 ± 4.6c <.0001 
20:4/18:2 0.61 ± 0.02a 0.94 ± 0.06bc 0.78 ± 0.02ab 1.04 ± 0.02c <.0001 
n-3 (% PUFA) 19.1 ± 2.7a 13.0 ± 1.1b 10.3 ± 0.5b 50.7 ± 1.3c <.0001 
 Juvenile NMR Young Adult NMR Old Adult NMR Young Adult Mice Significance of Difference 
N 
16:0 16.3 ± 2.3a 18.4 ± 0.6b 20.1 ± 0.9a 26.9 ± 0.4b <.0001 
16:1 n-7 1.9 ± 0.3a 0.9 ± 0.0b 1.0 ± 0.2b 1.5 ± 0.0a <.0001 
18:0 20.5 ± 0.7a 19.6 ± 0.3a 15.8 ± 0.7b 14.6 ± 0.3b <.0001 
18:1 n-9 15.6 ± 1.1a 7.5 ± 0.3b 6.4 ± 0.8b 6.8 ± 0.4b <.0001 
18:1 n-7 4.6 ± 0.2a 3.7 ± 0.1b 5.3 ± 0.2c 3.8 ± 0.1b <.0001 
18:2 n-6 15.5 ± 1.5a 19.3 ± 1.0b 23.2 ± 1.2c 9.3 ± 0.4d <.0001 
18:3 n-3 1.3 ± 0.2a 0.5 ± 0.1b 0.5 ± 0.2b 0.2 ± 0.0b <.0001 
20:2 n-6 2.5 ± 0.6a 0.4 ± 0.1b 0.2 ± 0.1b 0.4 ± 0.0b <.0001 
20:3 n-6 1.2 ± 0.2 0.9 ± 0.1 0.6 ± 0.1 1.3 ± 0.3 NS 
20:4 n-6 9.5 ± 1.1a 17.8 ± 0.5b 18.0 ± 0.8b 9.6 ± 0.2a <.0001 
22:4 n-6 1.0 ± 0.3a 1.7 ± 0.1b 1.8 ± 0.2b 0.6 ± 0.0a <.0001 
22:5 n-6 0.8 ± 0.3a 1.3 ± 0.1b 1.1 ± 0.1ab 0.8 ± 0.0a .01 
22:5 n-3 2.0 ± 0.1 2.7 ± 0.3 2.5 ± 0.1 2.6 ± 0.4 NS 
22:6 n-3 2.2 ± 0.1a 2.2 ± 0.3a 1.8 ± 0.1a 19.5 ± 0.5b <.0001 
% UFA 61.3 ± 3.4a 60.5 ± 0.4a 63.1 ± 1.2b 57.2 ± 0.4a .02 
% MUFA 23.4 ± 1.1a 12.6 ± 0.3b 12.9 ± 1.1b 12.8 ± 0.6b <.0001 
% PUFA 38.0 ± 3.7a 47.9 ± 0.7b 50.1 ± 2.1b 44.3 ± 1.0b .0005 
% n-6 PUFA 30.9 ± 3.9a 41.7 ± 1.0b 45.0 ± 2.0b 21.9 ± 0.2c <.0001 
% n-3 PUFA 7.0 ± 0.5a 6.2 ± 0.5a 5.1 ± 0.2a 22.5 ± 0.6b <.0001 
% C20-22 21.3 ± 2.1a 28.1 ± 1.0b 26.5 ± 0.9b 35.2 ± 0.9c <.0001 
Ave. CL 18.1 ± 0.1a 18.3 ± 0.0b 18.2 ± 0.0ab 18.6 ± 0.0c <.0001 
PI 110.6 ± 7.9a 148.0 ± 4.6b 143.6 ± 4.6b 231.3 ± 4.6c <.0001 
20:4/18:2 0.61 ± 0.02a 0.94 ± 0.06bc 0.78 ± 0.02ab 1.04 ± 0.02c <.0001 
n-3 (% PUFA) 19.1 ± 2.7a 13.0 ± 1.1b 10.3 ± 0.5b 50.7 ± 1.3c <.0001 

Notes: Fatty acids identified by number of C atoms:number of double bonds and position of terminal double bond.

Values are shown as mean ± standard error of mean (SEM).

Values with different superscripts are significantly different.

Values do not add up to 100% because only values for the major fatty acids (>.5%) are shown.

NS = no significant differences; UFA = unsaturated fatty acid; MUFA = monounsaturated fatty acid; PUFA = polyunsaturated fatty acid; PI = peroxidation index; Ave. CL = average chain length..

Supplemental Table 2.Fatty Acid Composition of Heart Phospholipids From Juvenile (0.25 Years), Young Adult (2 Years), and Old Adult (22 Years) Naked Mole-Rats (NMR) and Young Adult (0.25 Years) Mice.

 Juvenile NMR Young Adult NMR Old Adult NMR Young Adult Mice Significance of Difference 
N 
16:0 15.8 ± 2.1 15.1 ± 1.0 14.5 ± 1.1 17.0 ± 1.0 NS 
16:1 n-7 0.9 ± 0.1a 0.8 ± 0.1a 0.9 ± 0.2a 0.5 ± 0.0b .001 
18:0 20.7 ± 1.2a 17.2 ± 1.4a 16.7 ± 0.7a 20.4 ± 0.2a .02 
18:1 n-9 11.5 ± 1.4 9.1 ± 0.7 8.1 ± 0.3 8.0 ± 1.6 NS 
18:1 n-7 6.6 ± 0.2ab 5.9 ± 0.3a 7.6 ± 0.3b 3.2 ± 0.2c <.0001 
18:2 n-6 17.0 ± 2.3ab 16.6 ± 1.9ab 23.0 ± 0.9b 12.2 ± 1.8a .01 
18:3 n-3 0.5 ± 0.3ab 0.4 ± 0.1a 0.9 ± 0.1b 0.1 ± 0.0a .002 
20:3 n-6 1.0 ± 0.1a 0.5 ± 0.0b 0.4 ± 0.1b 0.6 ± 0.0b <.0001 
20:4 n-6 15.3 ± 2.4a 25.6 ± 3.4b 21.3 ± 1.3b 6.8 ± 0.2a <.0001 
20:5 n-3 1.6 ± 0.1a 0.6 ± 0.1b 0.6 ± 0.2b 0.2 ± 0.0c <.0001 
22:4 n-6 1.0 ± 0.3ab 1.5 ± 0.2b 1.5 ± 0.2b 0.4 ± 0.2a .003 
22:5 n-3 2.0 ± 0.2 2.0 ± 0.3 1.7 ± 0.3 1.3 ± 0.5 NS 
22:6 n-3 1.2 ± 0.2a 1.0 ± 0.1a 0.6 ± 0.1a 26.2 ± 1.8b <.0001 
% UFA 61.5 ± 4.0 66.2 ± 1.5 67.8 ± 2.2 61.5 ± 1.2 NS 
% MUFA 19.4 ± 1.8 16.7 ± 1.1 16.9 ± 0.6 12.5 ± 2.4 NS 
% PUFA 42.1 ± 5.7 49.5 ± 2.2 50.9 ± 1.6 49.0 ± 3.5 NS 
% n-6 PUFA 36.7 ± 5.5a 45.5 ± 2.3a 47.2 ± 1.1a 21.1 ± 1.6b <.0001 
% n-3 PUFA 5.4 ± 0.3a 4.0 ± 0.3a 3.8 ± 0.6a 28.0 ± 2.0b <.0001 
% C20-22 24.9 ± 3.2a 32.9 ± 3.5b 27.4 ± 2.1b 37.4 ± 1.4b .014 
Ave. CL 18.2 ± 0.1a 18.4 ± 0.1a 18.3 ± 0.1a 19.0 ± 0.1b <.0001 
PI 123.5 ± 15.2a 157.1 ± 12.5a 140.9 ± 8.8a 267.0 ± 15.6b <.0001 
20:4/18:2 0.90 ± 0.06 1.81 ± 0.56 0.93 ± 0.08 2.10 ± 1.74 NS 
n-3 (% PUFA) 13.2 ± 1.6a 8.2 ± 0.7b 7.3 ± 1.1b 57.1 ± 0.7c <.0001 
 Juvenile NMR Young Adult NMR Old Adult NMR Young Adult Mice Significance of Difference 
N 
16:0 15.8 ± 2.1 15.1 ± 1.0 14.5 ± 1.1 17.0 ± 1.0 NS 
16:1 n-7 0.9 ± 0.1a 0.8 ± 0.1a 0.9 ± 0.2a 0.5 ± 0.0b .001 
18:0 20.7 ± 1.2a 17.2 ± 1.4a 16.7 ± 0.7a 20.4 ± 0.2a .02 
18:1 n-9 11.5 ± 1.4 9.1 ± 0.7 8.1 ± 0.3 8.0 ± 1.6 NS 
18:1 n-7 6.6 ± 0.2ab 5.9 ± 0.3a 7.6 ± 0.3b 3.2 ± 0.2c <.0001 
18:2 n-6 17.0 ± 2.3ab 16.6 ± 1.9ab 23.0 ± 0.9b 12.2 ± 1.8a .01 
18:3 n-3 0.5 ± 0.3ab 0.4 ± 0.1a 0.9 ± 0.1b 0.1 ± 0.0a .002 
20:3 n-6 1.0 ± 0.1a 0.5 ± 0.0b 0.4 ± 0.1b 0.6 ± 0.0b <.0001 
20:4 n-6 15.3 ± 2.4a 25.6 ± 3.4b 21.3 ± 1.3b 6.8 ± 0.2a <.0001 
20:5 n-3 1.6 ± 0.1a 0.6 ± 0.1b 0.6 ± 0.2b 0.2 ± 0.0c <.0001 
22:4 n-6 1.0 ± 0.3ab 1.5 ± 0.2b 1.5 ± 0.2b 0.4 ± 0.2a .003 
22:5 n-3 2.0 ± 0.2 2.0 ± 0.3 1.7 ± 0.3 1.3 ± 0.5 NS 
22:6 n-3 1.2 ± 0.2a 1.0 ± 0.1a 0.6 ± 0.1a 26.2 ± 1.8b <.0001 
% UFA 61.5 ± 4.0 66.2 ± 1.5 67.8 ± 2.2 61.5 ± 1.2 NS 
% MUFA 19.4 ± 1.8 16.7 ± 1.1 16.9 ± 0.6 12.5 ± 2.4 NS 
% PUFA 42.1 ± 5.7 49.5 ± 2.2 50.9 ± 1.6 49.0 ± 3.5 NS 
% n-6 PUFA 36.7 ± 5.5a 45.5 ± 2.3a 47.2 ± 1.1a 21.1 ± 1.6b <.0001 
% n-3 PUFA 5.4 ± 0.3a 4.0 ± 0.3a 3.8 ± 0.6a 28.0 ± 2.0b <.0001 
% C20-22 24.9 ± 3.2a 32.9 ± 3.5b 27.4 ± 2.1b 37.4 ± 1.4b .014 
Ave. CL 18.2 ± 0.1a 18.4 ± 0.1a 18.3 ± 0.1a 19.0 ± 0.1b <.0001 
PI 123.5 ± 15.2a 157.1 ± 12.5a 140.9 ± 8.8a 267.0 ± 15.6b <.0001 
20:4/18:2 0.90 ± 0.06 1.81 ± 0.56 0.93 ± 0.08 2.10 ± 1.74 NS 
n-3 (% PUFA) 13.2 ± 1.6a 8.2 ± 0.7b 7.3 ± 1.1b 57.1 ± 0.7c <.0001 

Notes: Fatty acids identified by number of C atoms:number of double bonds and position of terminal double bond.

Values are shown as mean ± SEM (standard error of mean).

Values with different superscripts are significantly different.

Values do not add up to 100% because only values for the major fatty acids (<0.5%) are shown.

NS = no significant differences; UFA = unsaturated fatty acid; MUFA = monounsaturated fatty acid; PUFA = polyunsaturated fatty acid; PI = peroxidation index; Ave. CL = average chain length.

Supplemental Table 3.Fatty Acid Composition of Kidney Phospholipids From Juvenile (0.25 Years), Young Adult (2 Years), and Old Adult (22 Years) Naked Mole-Rats (NMR) and Young Adult (0.25 Years) Mice.

 Juvenile NMR Young Adult NMR Old Adult NMR Young Adult Mice Significance of Difference 
N 
16:0 19.3 ± 1.1a 19.2 ± 0.5a 18.7 ± 0.4a 21.7 ± 0.4b .004 
16:1 n-7 1.4 ± 0.1a 1.3 ± 0.1a 1.5 ± 0.3a 0.6 ± 0.0b <.0001 
18:0 18.9 ± 1.5 17.3 ± 0.4 16.6 ± 0.7 16.7 ± 0.3 NS 
18:1 n-9 13.4 ± 0.6a 12.7 ± 0.4a 11.7 ± 0.4ab 8.6 ± 1.3b .002 
18:1 n-7 6.3 ± 0.2a 6.0 ± 0.2a 7.3 ± 0.5b 2.9 ± 0.1c <.0001 
18:2 n-6 10.5 ± 1.7 10.4 ± 0.6 10.4 ± 0.7 10.9 ± 0.2 NS 
20:2 n-6 1.6 ± 0.5a 0.6 ± 0.1b 0.6 ± 0.2b 0.4 ± 0.0b .002 
20:3 n-6 1.3 ± 0.3 0.9 ± 0.0 0.9 ± 0.1 1.0 ± 0.1 NS 
20:4 n-6 16.5 ± 2.6a 20.4 ± 0.6ab 22.3 ± 0.7b 17.0 ± 0.7a .003 
20:5 n-3 1.4 ± 0.4a 0.6 ± 0.0a 0.8 ± 0.2a 0.9 ± 0.0b .002 
22:4 n-6 0.8 ± 0.3a 1.2 ± 0.0a 1.6 ± 0.2a 0.2 ± 0.0b <.0001 
22:5 n-3 1.6 ± 0.1a 1.3 ± 0.1a 1.6 ± 0.1a 0.5 ± 0.0b <.0001 
22:6 n-3 2.8 ± 0.2a 2.3 ± 0.3a 2.2 ± 0.2a 16.6 ± 1.1b <.0001 
% UFA 58.9 ± 3.8 61.0 ± 0.8 63.5 ± 1.5 60.6 ± 0.8 NS 
% MUFA 21.7 ± 0.8a 22.0 ± 0.7a 21.5 ± 0.3a 12.8 ± 1.3b <.0001 
% PUFA 37.2 ± 4.6a 39.0 ± 0.9a 42.0 ± 1.3ab 47.8 ± 0.8b .0007 
% n-6 PUFA 31.2 ± 4.9a 34.4 ± 0.9ab 36.9 ± 1.0b 29.7 ± 0.7a .03 
% n-3 PUFA 6.0 ± 0.3a 4.6 ± 0.2a 5.1 ± 0.4a 18.1 ± 1.1b <.0001 
% C20-22 26.7 ± 2.9a 29.4 ± 0.7a 32.0 ± 1.5a 37.4 ± 0.8b <.0001 
Ave. CL 18.2 ± 0.1a 18.3 ± 0.0a 18.3 ± 0.1a 18.7 ± 0.0b <.0001 
PI 127.4 ± 11.9a 137.4 ± 2.9a 148.7 ± 5.9a 226.4 ± 7.0b <.0001 
20:4/18:2 1.57 ± 0.09a 1.99 ± 0.12ab 2.17 ± 0.18b 1.56 ± 0.07c .002 
n-3 (% PUFA) 16.9 ± 2.8a 11.8 ± 0.7a 12.1 ± 0.5a 37.8 ± 1.8b <.0001 
 Juvenile NMR Young Adult NMR Old Adult NMR Young Adult Mice Significance of Difference 
N 
16:0 19.3 ± 1.1a 19.2 ± 0.5a 18.7 ± 0.4a 21.7 ± 0.4b .004 
16:1 n-7 1.4 ± 0.1a 1.3 ± 0.1a 1.5 ± 0.3a 0.6 ± 0.0b <.0001 
18:0 18.9 ± 1.5 17.3 ± 0.4 16.6 ± 0.7 16.7 ± 0.3 NS 
18:1 n-9 13.4 ± 0.6a 12.7 ± 0.4a 11.7 ± 0.4ab 8.6 ± 1.3b .002 
18:1 n-7 6.3 ± 0.2a 6.0 ± 0.2a 7.3 ± 0.5b 2.9 ± 0.1c <.0001 
18:2 n-6 10.5 ± 1.7 10.4 ± 0.6 10.4 ± 0.7 10.9 ± 0.2 NS 
20:2 n-6 1.6 ± 0.5a 0.6 ± 0.1b 0.6 ± 0.2b 0.4 ± 0.0b .002 
20:3 n-6 1.3 ± 0.3 0.9 ± 0.0 0.9 ± 0.1 1.0 ± 0.1 NS 
20:4 n-6 16.5 ± 2.6a 20.4 ± 0.6ab 22.3 ± 0.7b 17.0 ± 0.7a .003 
20:5 n-3 1.4 ± 0.4a 0.6 ± 0.0a 0.8 ± 0.2a 0.9 ± 0.0b .002 
22:4 n-6 0.8 ± 0.3a 1.2 ± 0.0a 1.6 ± 0.2a 0.2 ± 0.0b <.0001 
22:5 n-3 1.6 ± 0.1a 1.3 ± 0.1a 1.6 ± 0.1a 0.5 ± 0.0b <.0001 
22:6 n-3 2.8 ± 0.2a 2.3 ± 0.3a 2.2 ± 0.2a 16.6 ± 1.1b <.0001 
% UFA 58.9 ± 3.8 61.0 ± 0.8 63.5 ± 1.5 60.6 ± 0.8 NS 
% MUFA 21.7 ± 0.8a 22.0 ± 0.7a 21.5 ± 0.3a 12.8 ± 1.3b <.0001 
% PUFA 37.2 ± 4.6a 39.0 ± 0.9a 42.0 ± 1.3ab 47.8 ± 0.8b .0007 
% n-6 PUFA 31.2 ± 4.9a 34.4 ± 0.9ab 36.9 ± 1.0b 29.7 ± 0.7a .03 
% n-3 PUFA 6.0 ± 0.3a 4.6 ± 0.2a 5.1 ± 0.4a 18.1 ± 1.1b <.0001 
% C20-22 26.7 ± 2.9a 29.4 ± 0.7a 32.0 ± 1.5a 37.4 ± 0.8b <.0001 
Ave. CL 18.2 ± 0.1a 18.3 ± 0.0a 18.3 ± 0.1a 18.7 ± 0.0b <.0001 
PI 127.4 ± 11.9a 137.4 ± 2.9a 148.7 ± 5.9a 226.4 ± 7.0b <.0001 
20:4/18:2 1.57 ± 0.09a 1.99 ± 0.12ab 2.17 ± 0.18b 1.56 ± 0.07c .002 
n-3 (% PUFA) 16.9 ± 2.8a 11.8 ± 0.7a 12.1 ± 0.5a 37.8 ± 1.8b <.0001 

Notes: Fatty acids identified by number of C atoms:number of double bonds and position of terminal double bond.

Values are shown as mean ± SEM (standard error of mean).

Values with different superscripts are significantly different.

Values do not add up to 100% because only values for the major fatty acids (>.5%) are shown.

NS = no significant differences; UFA = unsaturated fatty acid; MUFA = monounsaturated fatty acid; PUFA = polyunsaturated fatty acid; PI = peroxidation index; Ave. CL = average chain length.

Supplemental Table 4.Fatty Acid Composition of Brain Phospholipids From Juvenile (0.25 Years), Young Adult (2 Years), and Old Adult (22 Years) Naked Mole-Rats (NMR) and Young Adult (0.25 Years) Mice.

 Juvenile NMR Young Adult NMR Old Adult NMR Young Adult Mice Significance of Difference 
N 
16:0 27.0 ± 1.1 26.3 ± 0.8 25.0 ± 1.0 24.1 ± 0.3 NS 
16:1 n-7 1.5 ± 0.2a 1.3 ± 0.1a 1.1 ± 0.1a 0.6 ± 0.0b <.0001 
18:0 20.3 ± 0.9 16.8 ± 2.2 20.4 ± 0.6 20.5 ± 0.3 NS 
18:1 n-9 16.2 ± 0.5a 17.6 ± 0.6ab 15.7 ± 0.6a 18.1 ± 0.2b .015 
18:1 n-7 4.7 ± 0.2a 5.0 ± 0.2a 5.1 ± 0.2a 4.4 ± 0.1b .018 
18:2 n-6 0.8 ± 0.1 0.7 ± 0.1 0.7 ± 0.1 0.6 ± 0.0 NS 
20:1 n-9 0.4 ± 0.2a 0.5 ± 0.1a 0.6 ± 0.1a 1.8 ± 0.1b <.0001 
20:4 n-6 10.3 ± 2.8a 12.7 ± 0.5a 13.2 ± 0.7a 8.6 ± 0.2b .008 
22:4 n-6 3.2 ± 0.3a 2.8 ± 0.2a 3.3 ± 0.3a 1.9 ± 0.0b .0002 
22:5 n-6 1.1 ± 0.1a 0.8 ± 0.1b 1.1 ± 0.1a 0.1 ± 0.0c <.0001 
22:6 n-3 10.5 ± 0.5a 11.1 ± 0.3a 10.8 ± 0.3a 15.1 ± 0.2b <.0001 
% UFA 51.8 ± 2.4 55.0 ± 1.5 53.2 ± 1.7 54.2 ± 0.5 NS 
% MUFA 23.0 ± 0.9a 25.7 ± 0.9ab 22.6 ± 0.8a 26.8 ± 0.8b .008 
% PUFA 28.8 ± 3.1 29.3 ± 1.0 30.7 ± 1.4 27.4 ± 0.3 NS 
% n-6 PUFA 16.4 ± 3.1a 17.7 ± 0.7a 19.3 ± 1.4a 11.8 ± 0.2b .002 
% n-3 PUFA 12.4 ± 1.1a 11.6 ± 0.3a 11.4 ± 0.2a 15.6 ± 0.2b <.0001 
% C20-22 28.5 ± 2.9 29.4 ± 0.9 30.7 ± 1.4 29.5 ± 0.2 NS 
Ave. CL 18.3 ± 0.1a 18.3 ± 0.0a 18.4 ± 0.1a 18.5 ± 0.0b .0009 
PI 154.9 ± 8.7 161.4 ± 5.0 165.7 ± 4.9 170.9 ± 2.0 NS 
20:4/18:2 13.2 ± 3.7 18.6 ± 1.1 18.4 ± 2.2 14.3 ± 1.0 NS 
n-3 (% PUFA) 44.3 ± 6.5a 39.8 ± 0.8a 37.3 ± 1.5a 56.9 ± 0.4b <.0001 
 Juvenile NMR Young Adult NMR Old Adult NMR Young Adult Mice Significance of Difference 
N 
16:0 27.0 ± 1.1 26.3 ± 0.8 25.0 ± 1.0 24.1 ± 0.3 NS 
16:1 n-7 1.5 ± 0.2a 1.3 ± 0.1a 1.1 ± 0.1a 0.6 ± 0.0b <.0001 
18:0 20.3 ± 0.9 16.8 ± 2.2 20.4 ± 0.6 20.5 ± 0.3 NS 
18:1 n-9 16.2 ± 0.5a 17.6 ± 0.6ab 15.7 ± 0.6a 18.1 ± 0.2b .015 
18:1 n-7 4.7 ± 0.2a 5.0 ± 0.2a 5.1 ± 0.2a 4.4 ± 0.1b .018 
18:2 n-6 0.8 ± 0.1 0.7 ± 0.1 0.7 ± 0.1 0.6 ± 0.0 NS 
20:1 n-9 0.4 ± 0.2a 0.5 ± 0.1a 0.6 ± 0.1a 1.8 ± 0.1b <.0001 
20:4 n-6 10.3 ± 2.8a 12.7 ± 0.5a 13.2 ± 0.7a 8.6 ± 0.2b .008 
22:4 n-6 3.2 ± 0.3a 2.8 ± 0.2a 3.3 ± 0.3a 1.9 ± 0.0b .0002 
22:5 n-6 1.1 ± 0.1a 0.8 ± 0.1b 1.1 ± 0.1a 0.1 ± 0.0c <.0001 
22:6 n-3 10.5 ± 0.5a 11.1 ± 0.3a 10.8 ± 0.3a 15.1 ± 0.2b <.0001 
% UFA 51.8 ± 2.4 55.0 ± 1.5 53.2 ± 1.7 54.2 ± 0.5 NS 
% MUFA 23.0 ± 0.9a 25.7 ± 0.9ab 22.6 ± 0.8a 26.8 ± 0.8b .008 
% PUFA 28.8 ± 3.1 29.3 ± 1.0 30.7 ± 1.4 27.4 ± 0.3 NS 
% n-6 PUFA 16.4 ± 3.1a 17.7 ± 0.7a 19.3 ± 1.4a 11.8 ± 0.2b .002 
% n-3 PUFA 12.4 ± 1.1a 11.6 ± 0.3a 11.4 ± 0.2a 15.6 ± 0.2b <.0001 
% C20-22 28.5 ± 2.9 29.4 ± 0.9 30.7 ± 1.4 29.5 ± 0.2 NS 
Ave. CL 18.3 ± 0.1a 18.3 ± 0.0a 18.4 ± 0.1a 18.5 ± 0.0b .0009 
PI 154.9 ± 8.7 161.4 ± 5.0 165.7 ± 4.9 170.9 ± 2.0 NS 
20:4/18:2 13.2 ± 3.7 18.6 ± 1.1 18.4 ± 2.2 14.3 ± 1.0 NS 
n-3 (% PUFA) 44.3 ± 6.5a 39.8 ± 0.8a 37.3 ± 1.5a 56.9 ± 0.4b <.0001 

Notes: Fatty acids identified by number of C atoms:number of double bonds and position of terminal double bond.

Values are shown as mean ± SEM (standard error of mean).

Values with different superscripts are significantly different.

Values do not add up to 100% because only values for the major fatty acids (<.5%) are shown.

NS = no significant differences; UFA = unsaturated fatty acid; MUFA = monounsaturated fatty acid; PUFA = polyunsaturated fatty acid; PI = peroxidation index; Ave. CL = average chain length.

Supplemental Table 5.Fatty Acid Composition of Liver Phospholipids From Juvenile (0.25 Years), Young Adult (2 Years), and Old Adult (22 years) Naked Mole-Rats (NMR) and Young Adult (0.25 Years) Mice.

 Juvenile NMR Young Adult NMR Old Adult NMR Young Adult Mice Significance of Difference 
N 
16:0 15.2 ± 1.1a 16.7 ± 0.5a 16.6 ± 0.5a 24.1 ± 0.9b <.0001 
16:1 n-7 1.0 ± 0.1 1.2 ± 0.2 0.9 ± 0.3 1.0 ± 0.2 NS 
18:0 27.1 ± 0.8a 25.6 ± 0.6a 25.3 ± 0.4a 18.0 ± 1.1b <.0001 
18:1 n-9 9.6 ± 1.0a 11.2 ± 0.4b 8.7 ± 0.3a 8.0 ± 0.2a .0002 
18:1 n-7 3.3 ± 0.1a 2.4 ± 0.2b 3.3 ± 0.2a 2.0 ± 0.1b .0002 
18:2 n-6 13.6 ± 0.6 13.7 ± 0.7 14.8 ± 0.2 14.8 ± 0.3 NS 
20:2 n-6 1.1 ± 0.4a 0.5 ± 0.1b 0.2 ± 0.0b 0.2 ± 0.0b .002 
20:3 n-6 1.6 ± 0.1 1.4 ± 0.1 1.3 ± 0.1 1.5 ± 0.1 NS 
20:4 n-6 12.8 ± 2.1a 14.4 ± 0.4ab 16.6 ± 0.3b 15.3 ± 0.3ab .03 
20:5 n-3 1.0 ± 0.3a 0.4 ± 0.1b 0.3 ± 0.1b 1.1 ± 0.1a .0003 
22:4 n-6 0.8 ± 0.3a 1.9 ± 0.2b 2.0 ± 0.2b 0.1 ± 0.0a <.0001 
22:5 n-6 1.4 ± 0.3a 2.1 ± 0.1b 2.0 ± 0.1b 0.1 ± 0.0c <.0001 
22:5 n-3 2.7 ± 0.4a 2.3 ± 0.2a 2.2 ± 0.1a 0.4 ± 0.0b <.0001 
22:6 n-3 6.5 ± 1.0a 3.2 ± 0.4b 3.2 ± 0.3b 11.7 ± 0.2c <.0001 
% UFA 56.3 ± 1.0 56.0 ± 0.4 56.6 ± 0.9 57.1 ± 0.4 NS 
% MUFA 14.2 ± 1.3a 15.4 ± 0.3a 13.2 ± 0.7bc 11.5 ± 0.4c .0002 
% PUFA 42.1 ± 1.9a 40.6 ± 0.3a 43.4 ± 0.4bc 45.6 ± 0.2c <.0001 
% n-6 PUFA 31.7 ± 2.8a 34.2 ± 0.5ab 36.9 ± 0.3b 32.2 ± 0.5a .01 
% n-3 PUFA 10.4 ± 1.5a 6.3 ± 0.4b 6.5 ± 0.4b 13.4 ± 0.4c <.0001 
% C20-22 28.3 ± 1.8a 26.7 ± 0.8a 28.1 ± 0.4ab 31.0 ± 0.3b .004 
Ave. CL 18.5 ± 0.1 18.3 ± 0.0 18.4 ± 0.0 18.4 ± 0.0 NS 
PI 157.6 ± 7.8a 139.5 ± 3.6b 147.1 ± 2.7ab 185.5 ± 1.7c <.0001 
20:4/18:2 0.94 ± 0.16 1.08 ± 0.08 1.12 ± 0.03 1.04 ± 0.03 NS 
n-3 (% PUFA) 24.9 ± 4.1a 15.6 ± 1.1b 15.0 ± 0.7b 29.4 ± 0.8a <.0001 
 Juvenile NMR Young Adult NMR Old Adult NMR Young Adult Mice Significance of Difference 
N 
16:0 15.2 ± 1.1a 16.7 ± 0.5a 16.6 ± 0.5a 24.1 ± 0.9b <.0001 
16:1 n-7 1.0 ± 0.1 1.2 ± 0.2 0.9 ± 0.3 1.0 ± 0.2 NS 
18:0 27.1 ± 0.8a 25.6 ± 0.6a 25.3 ± 0.4a 18.0 ± 1.1b <.0001 
18:1 n-9 9.6 ± 1.0a 11.2 ± 0.4b 8.7 ± 0.3a 8.0 ± 0.2a .0002 
18:1 n-7 3.3 ± 0.1a 2.4 ± 0.2b 3.3 ± 0.2a 2.0 ± 0.1b .0002 
18:2 n-6 13.6 ± 0.6 13.7 ± 0.7 14.8 ± 0.2 14.8 ± 0.3 NS 
20:2 n-6 1.1 ± 0.4a 0.5 ± 0.1b 0.2 ± 0.0b 0.2 ± 0.0b .002 
20:3 n-6 1.6 ± 0.1 1.4 ± 0.1 1.3 ± 0.1 1.5 ± 0.1 NS 
20:4 n-6 12.8 ± 2.1a 14.4 ± 0.4ab 16.6 ± 0.3b 15.3 ± 0.3ab .03 
20:5 n-3 1.0 ± 0.3a 0.4 ± 0.1b 0.3 ± 0.1b 1.1 ± 0.1a .0003 
22:4 n-6 0.8 ± 0.3a 1.9 ± 0.2b 2.0 ± 0.2b 0.1 ± 0.0a <.0001 
22:5 n-6 1.4 ± 0.3a 2.1 ± 0.1b 2.0 ± 0.1b 0.1 ± 0.0c <.0001 
22:5 n-3 2.7 ± 0.4a 2.3 ± 0.2a 2.2 ± 0.1a 0.4 ± 0.0b <.0001 
22:6 n-3 6.5 ± 1.0a 3.2 ± 0.4b 3.2 ± 0.3b 11.7 ± 0.2c <.0001 
% UFA 56.3 ± 1.0 56.0 ± 0.4 56.6 ± 0.9 57.1 ± 0.4 NS 
% MUFA 14.2 ± 1.3a 15.4 ± 0.3a 13.2 ± 0.7bc 11.5 ± 0.4c .0002 
% PUFA 42.1 ± 1.9a 40.6 ± 0.3a 43.4 ± 0.4bc 45.6 ± 0.2c <.0001 
% n-6 PUFA 31.7 ± 2.8a 34.2 ± 0.5ab 36.9 ± 0.3b 32.2 ± 0.5a .01 
% n-3 PUFA 10.4 ± 1.5a 6.3 ± 0.4b 6.5 ± 0.4b 13.4 ± 0.4c <.0001 
% C20-22 28.3 ± 1.8a 26.7 ± 0.8a 28.1 ± 0.4ab 31.0 ± 0.3b .004 
Ave. CL 18.5 ± 0.1 18.3 ± 0.0 18.4 ± 0.0 18.4 ± 0.0 NS 
PI 157.6 ± 7.8a 139.5 ± 3.6b 147.1 ± 2.7ab 185.5 ± 1.7c <.0001 
20:4/18:2 0.94 ± 0.16 1.08 ± 0.08 1.12 ± 0.03 1.04 ± 0.03 NS 
n-3 (% PUFA) 24.9 ± 4.1a 15.6 ± 1.1b 15.0 ± 0.7b 29.4 ± 0.8a <.0001 

Notes: Fatty acids identified by number of C atoms:number of double bonds and position of terminal double bond.

Values are shown as mean ± SEM (standard error of mean).

Values with different superscripts are significantly different.

Values do not add up to 100% because only values for the major fatty acids (>.5%) are shown.

NS = no significant differences; UFA = unsaturated fatty acid; MUFA = monounsaturated fatty acid; PUFA = polyunsaturated fatty acid; PI = peroxidation index; Ave. CL = average chain length.

Supplemental Table 6.Fatty Acid Composition of Liver Mitochondrial Phospholipids From Young Adult (2 Years) Naked Mole-Rats (NMR) and Young Adult (0.25 Years) Mice.

 Young Adult NMR Young Adult Mice Significance of Difference 
N 
16:0 17.6 ± 0.7 26.1 ± 0.7 <.0001 
16:1 n-7 1.1 ± 0.2 1.1 ± 0.1 NS 
18:0 24.4 ± 1.1 16.9 ± 0.9 .0001 
18:1 n-9 11.5 ± 0.6 8.7 ± 0.3 .0008 
18:1 n-7 2.4 ± 0.2 2.0 ± 0.1 NS 
18:2 n-6 14.3 ± 0.9 14.1 ± 0.6 NS 
20:3 n-6 1.3 ± 0.1 1.4 ± 0.1 NS 
20:4 n-6 14.8 ± 0.7 14.2 ± 0.3 NS 
20:5 n-3 0.6 ± 0.1 1.1 ± 0.1 .002 
22:4 n-6 1.7 ± 0.2 0.1 ± 0.0 <.0001 
22:5 n-6 2.0 ± 0.2 0.1 ± 0.0 <.0001 
22:5 n-3 2.2 ± 0.1 0.4 ± 0.0 <.0001 
22:6 n-3 3.2 ± 0.5 12.0 ± 0.3 <.0001 
% UFA 56.5 ± 0.5 56.1 ± 0.4 NS 
% MUFA 15.4 ± 0.5 12.2 ± 0.5 .0005 
% PUFA 41.1 ± 0.9 43.8 ± 0.4 .015 
% n-6 PUFA 34.8 ± 1.0 30.2 ± 0.7 .0014 
% n-3 PUFA 6.3 ± 0.5 13.6 ± 0.4 <.0001 
% C20-22 26.4 ± 1.1 29.9 ± 0.3 .007 
Ave. CL 18.3 ± 0.0 18.3 ± 0.0 NS 
PI 139.5 ± 5.7 181.4 ± 2.1 <.0001 
20:4/18:2 1.05 ± 0.08 1.01 ± 0.04 NS 
n-3 (% PUFA) 50.7 ± 1.3 31.0 ± 1.0 <.0001 
 Young Adult NMR Young Adult Mice Significance of Difference 
N 
16:0 17.6 ± 0.7 26.1 ± 0.7 <.0001 
16:1 n-7 1.1 ± 0.2 1.1 ± 0.1 NS 
18:0 24.4 ± 1.1 16.9 ± 0.9 .0001 
18:1 n-9 11.5 ± 0.6 8.7 ± 0.3 .0008 
18:1 n-7 2.4 ± 0.2 2.0 ± 0.1 NS 
18:2 n-6 14.3 ± 0.9 14.1 ± 0.6 NS 
20:3 n-6 1.3 ± 0.1 1.4 ± 0.1 NS 
20:4 n-6 14.8 ± 0.7 14.2 ± 0.3 NS 
20:5 n-3 0.6 ± 0.1 1.1 ± 0.1 .002 
22:4 n-6 1.7 ± 0.2 0.1 ± 0.0 <.0001 
22:5 n-6 2.0 ± 0.2 0.1 ± 0.0 <.0001 
22:5 n-3 2.2 ± 0.1 0.4 ± 0.0 <.0001 
22:6 n-3 3.2 ± 0.5 12.0 ± 0.3 <.0001 
% UFA 56.5 ± 0.5 56.1 ± 0.4 NS 
% MUFA 15.4 ± 0.5 12.2 ± 0.5 .0005 
% PUFA 41.1 ± 0.9 43.8 ± 0.4 .015 
% n-6 PUFA 34.8 ± 1.0 30.2 ± 0.7 .0014 
% n-3 PUFA 6.3 ± 0.5 13.6 ± 0.4 <.0001 
% C20-22 26.4 ± 1.1 29.9 ± 0.3 .007 
Ave. CL 18.3 ± 0.0 18.3 ± 0.0 NS 
PI 139.5 ± 5.7 181.4 ± 2.1 <.0001 
20:4/18:2 1.05 ± 0.08 1.01 ± 0.04 NS 
n-3 (% PUFA) 50.7 ± 1.3 31.0 ± 1.0 <.0001 

Notes: Fatty acids identified by number of C atoms:number of double bonds and position of terminal double bond.

Values are shown as mean ± SEM (standard error of mean).

Values with different superscripts are significantly different.

Values do not add up to 100% because only values for the major fatty acids (>.5%) are shown.

NS = no significant differences; UFA = unsaturated fatty acid; MUFA = monounsaturated fatty acid; PUFA = polyunsaturated fatty acid; PI = peroxidation index; Ave. CL = average chain length.

A. J. Hulbert was supported by a Fulbright Senior Scholar award and grants (DP0450178 and DP0557448) from the Australian Research Council. S.C.F. is supported by an Australian Postgraduate Award. R.B. is supported by grants from the National Institutes of Health (NIH-AG022891-01 and NIGM S06-GM08168).

The Animal Care Staff at City College of New York is gratefully thanked for their assistance in the care of these animals, and Yael Edrey and Mario Pinto are thanked for their assistance in the laboratory at City College of New York.

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Author notes

1Metabolic Research Centre, 2School of Biological Sciences, and 3Department of Biomedical Sciences, University of Wollongong, New South Wales, Australia.