EXG-09487; No of Pages 6

Experimental Gerontology xxx (2014) xxxxxx

Contents lists available at ScienceDirect

Experimental Gerontology
journal homepage: www.elsevier.com/locate/expgero

High corn oil dietary intake improves health and longevity of aging mice

2Q3

Hongwei Si a,, Longyun Zhang a, Siqin Liu a, Tanya LeRoith b, Carlos Virgous c

3Q4
4
5

a r t i c l e

7
8
9
10
11
12
13

Article history:
Received 15 July 2014
Received in revised form 29 August 2014
Accepted 2 September 2014
Available online xxxx

14
15
16
17
18

Keywords:
Corn oil
Aging mice
Longevity
Health

i n f o

R
O

Department of Family and Consumer Sciences, Tennessee State University, Nashville, TN 37209, United States
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, United States
Animal Care Facility, Meharry Medical College, Nashville, TN 37208, United States

a b s t r a c t

Corn oil has been recommended as a replacement for saturated fats because of its high levels of poly- and monounsaturated fatty acids. In the present study, we tested whether very high levels of corn oil (58.6% fat-derived calories, FDC) intake improve health and longevity of aging mice. Twelve month old male C57BL/6 mice were fed a
normal diet (10% FDC of corn oil, N) or a high fat diet (58.6% FDC of corn oil, HF) for 1315 months. Our results
show that a HF diet signicantly increased the longevity of the aged mice (at 25 months of age, 53.8% of mice died
in the N group, whereas the mortality rate was only 23.2% in the HF group). High corn oil also reversed agingincreased blood lipids including triglyceride, total cholesterol and LDL. Similarly, high corn oil intake overturned
aging-raised pro-inammatory markers including IL-1, IL-6, and monocyte chemotactic protein-1 (MCP-1) in
the blood. In addition, corn oil intake reversed aging-damaged rotarod performance and liver function. Interestingly, the HF group was signicantly heavier than the N group (53.6 g/mouse vs. 41.3 g/mouse); however, both
HF and N groups had the same calorie intake (12.48 kcal/d/mouse vs. 12.24 kcal/d/mouse). Although, the HF
group's food consumption was lower than that of the N group (2.4 g/d/mouse vs. 3.4 g/d/mouse). These results
suggest that if total calorie consumption stays in the normal range, very high levels of corn oil intake improve
health and longevity of aging mice.
2014 Published by Elsevier Inc.

37
35
34

36

1. Introduction

39

High saturated fat diets are well associated with obesity prevalence
and the increased risk of cardiovascular disease, diabetes and cancer.
Reducing saturated fats from the diet is recommended to eliminate
Western diet-induced health problems. The common alternatives of
animal (saturated) fats for humans are plant oil, including soybean oil,
peanut oil and corn oil because of the high percentage of unsaturated
fat acids.
Corn oil is composed mainly (99% of the rened or 96% of the crude
oil) of acylglycerols (mono-, di- and primarily tri-), and has 59% polyunsaturated (PUFA), 24% monounsaturated (MUFA) and 13% saturated
fatty acid (SFA). The PUFA to SFA ratio (P/S) is about 4.6. Corn oil has one
of the highest PUFA levels after sunower, safower, walnut and wheat
germ oil (Landers and Rathmann, 1981). The primary PUFA is linoleic
acid (C18:2n 6), with a small amount of linolenic acid (C18:3n 3)

48
49
50
51
52

N
C
O

46
47

44
45

38

42
43

19
20
21
22
23
24
25
26
27
28
29
30
31
32

Section Editor: Holly M Brown-Borg

33

40
41

Abbreviations: BW, body weight; EFAs, essential fatty acids; FDC, fat-derived calories;
GSR, glutathione-disulde reductase; GSH, glutathione; H&E, hematoxylin and eosin;
HDL, high-density lipoprotein; HF, high corn oil diet; IFN-, interferon gamma; IL, interleukin; KC, keratinocyte chemoattractant; LDL, low-density lipoprotein; MCP-1, macrophage
chemoattractant protein-1; MUFA, monounsaturated fatty acid; N, normal diet; PUFA, polyunsaturatedfatty acid; ROS,reactive oxygen species; SFA,saturatedfatty acid; SOD,superoxide dismutase; TNF, tumor necrosis factor-; YC, youth control.
Corresponding author.
E-mail address: hsi@tnstate.edu (H. Si).

giving a n 6/n3 ratio of 83. Corn oil contains a signicant amount

of ubiquinone and high amounts of gamma-tocopherols (vitamin
E) (Dupont et al., 1990). These high contents of PUFA and vitamin E
may contribute to the health benets of corn oil consumption.
The benecial effects of PUFA have been extensively investigated,
however, there are very few studies investigating the effects on human
health with long-term corn oil consumption, particularly on the older
population. This is very important because corn oil is the second leading
vegetable oil consumed in the United States (USDA, 2014). Since U.S.
adults age 65 and older heavily consume this high fat oil, their population
is rapidly increasing and is projected to reach 71 million by 2030. The objectives of the present study are to investigate the long-term health effect
of high volume of corn oil consumption in aging mice and to understand
the relevant mechanisms.

53

2. Methods and Materials

67

2.1. Experimental Animals and Diets

68

Twelve-month old male C57BL/6 mice were purchased from the

National Cancer Institute (Bethesda, MD). Mice were housed in an
environmentally-controlled (23 2 C; 12-h light: dark cycle) animal
facility and they were given ad libitum access to food and water. To
test the health effect of high corn oil intake, mice were randomly divided into two groups (n = 31) and given either a normal diet (N) or a high

69

http://dx.doi.org/10.1016/j.exger.2014.09.001
0531-5565/ 2014 Published by Elsevier Inc.

Please cite this article as: Si, H., et al., High corn oil dietary intake improves health and longevity of aging mice, Exp. Gerontol. (2014), http://
dx.doi.org/10.1016/j.exger.2014.09.001

54
55
56
57
58
59
60
61
62
63
64
65
66

70
71
72
73
74

2.3. Pathological Analysis

117

120

Fresh livers were xed in 10% phosphate buffered neutral formalin,

embedded in parafn, cut at thicknesses of 5 m, and then stained
with hematoxylin and eosin (H&E) for histological examination of
hepatic lesions. Three sections from each mouse were examined. The

t1:1
t1:2

Table 1
Diet composition and energy distribution.

107
108
109
110
111
112
113
114

118
119

t1:3

105
106

98
99

96
97

94
95

92
93

90
91

88
89

126

2.5. Statistical Analysis

Ingredient

t1:4

Casein

t1:5
t1:6
t1:7
t1:8
t1:9
t1:10
t1:11
t1:12
t1:13
t1:14

L-Cystine

Sucrose
Corn starch
Dyetrose
Corn oil
Cellulose
Mineral mix #210050
Vitamin mix #310025
Choline bitartrate
Total

Normal diet (N)

High fat diet (HF)

g/kg

g/kg

kcal/kg

kcal/kg

140
1.8

501.2
7.2

226.8
3

811.9
12.0

100
465.7
155
40
50
35
10
2.5
1000.00

400
1676.52
589
360
0
29.4
38.7
0
3602.02

100
75.7
155
340
50
35
10
2.5
1000.00

400
272.52
589
3060
0
30.8
38.7
0
5214.96

123
124

127
128
129
130
131
132
Q5
133
134

The longevity curves were plotted using the KaplanMeier method

including all available mice at each time point (Baur et al., 2006), and
the Logrank test was applied to compare the distributions of the different groups. The results from the pathological analysis of the liver were
analyzed using the KruskalWallis test, and signicant differences
between treatment groups were further analyzed using the Mann
Whitney-U test. All other data were analyzed with one-way ANOVA
and signicant differences between treatment groups were further
analyzed using the t-test. P-values less than 0.05 were considered to
be statistically signicant (*, P b 0.05; **, P b 0.01).

135
136
137
138
139
140
141
142
143
144

3. Results

145

3.1. Longevity

146

At 25 months of age, 53.8% of mice had died in the N group, whereas

the mortality rate was only 23.2% in the HF group (P = 0.02, Fig. 1). The
median for the HF group was reached two months later at 27 months of
age. While the sample size (n = 31/group) was relatively small for a
typical longevity study, we think that the observed effects of high corn
oil on the longevity of aging mice is a real action of this compound because such a large difference between the two groups was unlikely
due to random variation.

147
148

3.2. Similar Energy Intake

155

149
150
151
152
153
154

Although the average BW in the HF group was signicantly higher 156

than that in the N group as shown in Fig. 2A, the food consumption 157
in the HF group was signicantly lower than that in the N group 158

120
100

86
87

Rotarod assay, a simple and accurate approach to examining agerelated changes in balance and motor coordination (Baur et al., 2006),
was performed using the rotarod apparatus (Med Associates, St. Albans
VT) at 14 and 25 month old mice to examine their ability to remain on
an revolving rod (Coyle et al., 2008). Briey, a mouse was briey placed
in a separate lane of a rotarod with an accelerating speed (220 rpm)
until the mouse fell off the rod. The length of time and speed of the
mouse which stayed on the rod were recorded.

116

84
85

125

115

Serum total cholesterol, HDL-cholesterol, and triglycerides in mice

were measured using a PTS CardioChek Blood Analysis Meter (Maria
Stein, OH) according to the manufacturer's instructions and our previous report (Si et al., 2011). LDL-cholesterol was calculated using the formula from the manual of the analysis meter: LDL-cholesterol = total
cholesterol HDL-cholesterol triglyceride / 5. Serum cytokines
and chemokines including interleukin (IL)-6, IL-1, IL-10, tumor necrosis factor- (TNF), keratinocyte chemoattractant (KC), monocyte chemotactic protein 1(MCP-1) and interferon gamma (IFN-) were tested
by a Luminex mouse cytokine array assay (Capital Biosciences, MD) as
previously described (Si et al., 2011; Veenbergen et al., 2010). The activity of glutathione-disulde reductase (GSR) in the liver was measured
as we previously described (Si et al., 2011).

82
83

2.4. Rotarod Test

R
O

103
104

81

2.2. Measurements of Serum Biological Markers and Hepatic Antioxidants

79
80

121
122

102

77
78

pathological alterations in the liver were scored according to the levels

of vacuolar changes (hydropic degeneration or lipidosis) in hepatocytes
(1 = 010%, 2 = 1030%, 3 = 3050%, and 4 50% of hepatocytes
affected).

100
101

corn oil diet (HF). Both diets are based on the AIN-93 produced by Dyets
Inc. (Bethlehem, PA) with two exceptions: 1) soybean oil was replaced
with corn oil and 2) the percentage of corn oil in each diet. The normal
diet has 10% fat derived calories (FDC) and the HF diet has 58% fat derived calories (FDC) (Reeves et al., 1993). This dose of corn oil (58%
FDC) was calculated based on previous studies using high fat diet (60%
FDC, 6% from soybean oil and 54% from lard) (Sung et al., 2014). Detailed
compositions of the diets are listed in Table 1. To ensure the stability of
the corn oil, diets were stored at 4 C and were kept away from light. The
diets were replaced every week. Body weight (BW) and food consumption were monitored weekly. The general health and well-being of the
mice were monitored daily. If a mouse was reported as or marked as
sick, the criteria for euthanizing mice were independently assessed by
a veterinarian adhering to the Institutional Animal Care and Use Committee guidelines. Mice with a BW less than 30% of their original BW
and other critical conditions including severe ulcerative dermatitis, urinary obstruction and abdominal masses were euthanized by inhalation
of CO2 and censored. When the median for the control group was
reached, the remaining 14 mice from the control group and 12 mice
from the HF group were fasted overnight and euthanized using CO2,
and their blood and tissues were collected for biochemical and physiological analysis. The HF group continued until the median was reached.
We also collected blood and tissues from youth control mice (12-month
old, 12 mice, YC) to compare the changes of biochemical and physiological analysis with the other two groups. The animal protocol was
approved by the Institutional Animal Care and Use Committee at
Meharry Medical College.

Survival Rate (%)

75
76

H. Si et al. / Experimental Gerontology xxx (2014) xxxxxx

80
60
40

N
HF

20
0
12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27

Age: month
Fig. 1. Longevity curve in normal diet (N) and high corn oil diet (HF) mice for 1315 months.
There initially was 31 mice/group. *P b 0.05.
Q1

Please cite this article as: Si, H., et al., High corn oil dietary intake improves health and longevity of aging mice, Exp. Gerontol. (2014), http://
dx.doi.org/10.1016/j.exger.2014.09.001

60

Food intake (g/mouse/d)

H. Si et al. / Experimental Gerontology xxx (2014) xxxxxx

Body weight (g)

50
40
30
N
HF

20
10
0

12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27

4.0

3.0
2.0
1.0
0.0

12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27

F
O

R
O

8.0

N
HF

4.0

12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27

Energy intake (Kcal/mouse/d)

Age:month

12

0.0

N
HF

Age:month
16

Age:month

159
160

164

3.3. Maintained Rotarod Performance

165
166

Physical activity and locomotor function continuously diminishing

with aging (Baur et al., 2006; Yankner et al., 2008) and although corn
oil increased longevity, it is important to know whether the quality of
life was maintained. We evaluated the ability to perform on a rotarod,
a classic method of testing balance and motor coordination. While the
time on the rod was signicantly decreased as mice aged in the N
group (decreased from 115 s at month 14 to 80 s at month 25), the

171

E
R

150
120

N
C
O

169
170

167
168

Time on rod(s)

161
162

163

(Fig. 2B). This may be a result of the texture of the HF diet, which has the
consistency of paste. Some days an oily liquid would form on the top of
the rodent feeding jars, while the N diets were typical pellets. Interestingly, there was no signicant difference in energy intake between
these two groups (Fig. 2C).

Fig. 2. Curves of body weight (A), food intake (B) and energy intake (C) in normal diet (N) and high corn oil diet (HF) mice for 1315 months. There initially was 31 mice/group. *P b 0.05.

90
60
30
0

N
HF
Mo: 14

N
HF
Mo: 25

Fig. 3. Corn oil maintained rotarod performance in both normal diet (N) and high corn oil
diet (HF) mice at 14 and 25 months of age. Data are means SE, n = 12 mice/group.
*P b 0.05.

HF group maintained their motor skills until they were 25 months of 172
age (Fig. 3).
173
3.4. Improved Hepatic Pathology

174

Histological examination of liver sections stained with hematoxylin

and eosin revealed a loss of cellular integrity and the accumulation of
large lipid droplets in the livers of the N group, but the HF group reduced
the size of intracytoplasmic lipid vacuoles. Blinded scoring of the liver
sections for overall pathology on a scale of 04 (with 4 being the most
severe) gave mean values of 2.5 for the N group, 1.8 for the HF group
and 0.8 for the YC group (Fig. 4).

175

3.5. Lowered Serum Lipids

182

Circulating lipid abnormalities are increasingly recognized as

playing an important role in the aging process and age-related disorders such as diabetes and vascular dysfunction (Labinskyy et al.,
2006). Compared to the YC group, serum triglyceride, total cholesterol
and LDL-cholesterol were signicantly increased in the N group; however,
all these three serum lipids were reversed in the HF group as shown in
Table 2.

183
184

3.6. Decreased Serum Inammatory Cytokines

190

Consistent with observations of the pathological alterations in the

liver and remarkably shortened lifespan of mice in the N group, circulating levels of cytokines including IL-1, IL-6, IFN- and MCP-1 were signicantly elevated in the N group compared to those in the YC group
(Table 3). However, dietary consumption of corn oil signicantly reduced these pro-inammatory markers (Table 3), indicating that corn
oil may suppress chronic inammation caused by aging. In addition,
GSR activity in the livers of the N group was signicantly decreased

191

Please cite this article as: Si, H., et al., High corn oil dietary intake improves health and longevity of aging mice, Exp. Gerontol. (2014), http://
dx.doi.org/10.1016/j.exger.2014.09.001

176
177
178
179
180
181

185
186
187
188
189

192
193
194
195
196
197
198

H. Si et al. / Experimental Gerontology xxx (2014) xxxxxx

1.0
0

YC

HF

Fig. 4. Corn oil improved hepatic pathology in aging mice. Hematoxylin and eosin stained slides of liver (three sections from each mouse) from young control (YC), normal diet (N) and
high corn oil diet (HF) mice were scored and the number of mice at relevant categories based on the levels of vacuolar change (hydropic degeneration or lipidosis for the liver) was
reported. A set of representative images and bar graphs (means SE, n = 1214/group) were shown. The arrows point to intracytoplasmic lipid vacuoles. 200 magnication. Scale
bar = 50 um. *P b 0.05.

Q2

R
O

2.0

3.0

4.0

HF

Pathological alterations
of liver ( arbitrary unit)

YC

compared to that in the YC group, whereas the activity of this enzyme

was reversed in the HF group (data no shown).

201

4. Discussion

202
203

218

Aging is well-known as an inevitable process that is physiologically

characterized as a progressive, generalized systematic dysfunction of
almost or all organs, giving rise to the escalated vulnerability to environmental challenges and resulting in increased risks of disease and death.
Indeed, aging is associated with a greatly increased metabolic and oxidative stress, elevated chronic, low-grade inammation, and accumulated DNA mutations as well as increased levels of its DNA damages
(Frisard and Ravussin, 2006; Heininger, 2000a,b). It is established that
calorie restriction delays age-associated organ disorders and increases
longevity as well as improves inammation and oxidative stress in a
wide range of species, suggesting that targeting nutrient-sensing and
energy metabolism pathways may be an effective approach to delay
the aging process and age-related diseases. In the present study, we
found that high level of corn oil (58.6% FDC) intake improved health
and longevity of aging mice, which may be associated with reversing
aging-increased blood lipids and pro-inammatory makers as well as
aging-damaged rotarod performance test and liver function. To our

t2:1
t2:2

Table 2
Blood lipid levels (mg/dL).

210
211
212
213
214
215
216
217

208
209

206
207

204
205

199
200

t2:3

Group

Triglyceride

Total cholesterol

LDL

HDL

t2:4
t2:5
t2:6

YC
N
HF

115 9
142 15
124 12

197 19
314 26
171 15

135 22
240 23
113 11

39 1
52 7
40 3

t2:7
t2:8

Values are means SE (n = 1214 per group).

P b 0.05.

knowledge, the present study is the rst study that shows that if total
calorie intake is kept in the normal range, long-term very high level of
corn oil intake can improve health and increase longevity of aging mice.
A large body of evidence indicates that increased generation of reactive oxygen species (ROS) which are chemically reactive molecules with
most of them containing oxygen and unpaired electrons is one of the
major triggers of aging. There is a strong correlation between chronological age and the levels of ROS generation and oxidative damage of
tissues. ROS are primarily produced by mitochondria during energy production (about 2% of total oxygen consumption was funneled to ROS)
(Chance et al., 1979). Extra amounts of ROS induces oxidation of fatty
acids and proteins and causes oxidative damage of DNA that may lead
to cellular senescence, functional alterations, and pathological conditions (Harman, 1972; Linnane et al., 1989). This extra amount of ROS
is deactivated to water and oxygen by endogenous enzymes including
superoxide dismutase (SOD), catalase or glutathione peroxidases
(Chang et al., 2004). Endogenous antioxidant glutathione (GSH) and exogenous antioxidants including vitamins C and E are also important ROS
scavengers. Reducing ROS is proposed as a leading strategy to delay
aging and related degenerative diseases. Corn oil is one of the highest
natural sources of vitamin E (62.01 mg/100 g oil) and is just a little
less than cottonseed oil (62.37 mg/100 g oil). This high content of vitamin E may prevent aging-increased ROS and extend the lifespan of
aging mice. This is supported by our results showing that a decreased
GSR activity, a critical endogenous antioxidant enzyme, was reversed
by corn oil intake (data not shown).
Aging-induced ROS also contributes to low-grade chronic inammation (Brod, 2000), a crucial player of the process of aging and agerelated diseases in older adults. Indeed, chronic pro-inammatory
markers including IL-6, MCP-1 and TNF- are consistently elevated
with age in the absence of acute infection or other physiological stress
(Ferrucci et al., 2005). Consequently, the sustained increases of these

Please cite this article as: Si, H., et al., High corn oil dietary intake improves health and longevity of aging mice, Exp. Gerontol. (2014), http://
dx.doi.org/10.1016/j.exger.2014.09.001

219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
Q6
243
244
245
246
247
248
249
250

H. Si et al. / Experimental Gerontology xxx (2014) xxxxxx

Table 3
Serum inammatory cytokines (pg/ml).
IL-1

IL-6

IL-10

IFN

TNF

KC

MCP-1

26.3 10.8
43.4 15.9
26.2 8.4

17.5 6.7
57.7 11.6
20.2 9.6

1.9 0.0
4.9 1.0
13.1 4.0

43.9 10.2
110.0 28.5
99.0 24.7

9.1 3.9
6.8 2.2
6.4 2.0

42.2 16.2
43.5 6.6
55.3 3.3

62.2 15.2
310.0 27.5
198.0 18.3

pro-inammatory molecules impair the function and integrity of various tissues and organs and thus accelerate aging and aging-related
chronic diseases, although this increase is still in the sub-acute range
(Chung et al., 2006). Interestingly, calorie restriction signicantly
attenuates the increase of these pro-inammatory markers while extending the lifespan (Chung et al., 2006; Zou et al., 2004), suggesting
that anti-inammatory agents may have the potential to extend a
healthy lifespan. Results from the present study show that dietary intake of corn oil signicantly reversed the increase of circulating proinammatory markers including IL-1, IL-6, IFN- and MCP-1 in aging
mice and therefore increased longevity.
Elevated LDL-cholesterol is well known as one of the major risks of
cardiovascular disease and reducing blood LDL is recommended to
lower cardiovascular disease as well as other aging-related chronic diseases (NCEP, 2002). Corn oil has been found to be highly effective in
lowering blood cholesterol, particularly LDL-cholesterol (Ahrens et al.,
1957; Hill et al., 1979). Our results are in line with these previous studies
that corn oil lowers LDL-cholesterol, total cholesterol and triglyceride. This effect may be due to the high PUFA, which is supported by
evidence that corn oil is more effective than olive oil in lowering
LDL-cholesterol because corn oil has higher PUFA (58.7 g/100 g oil)
than olive oil (8.4 g/100 g oil) (Dupont et al., 1990; Howell et al.,
1998). Corn oil has a plant sterol content of 128 mg/1000 kcal vs.
66 mg/1000 kcal for olive oil, and these plant sterols can reduce cholesterol absorption from the gut which in turn lowers body pools and
enhances synthesis rate through de-suppression of cellular hydroxymethylglutaryl-CoA reductase activity (Howell et al., 1998).
A lower ratio of omega-6/omega-3 fatty acids (n6/n3) is recommended to reduce the risk of many highly prevalent chronic diseases in
Western societies (ratio of n6/n3 in Western diets is 15/116.7/1
(Simopoulos, 2002). Mammalian cells cannot convert omega-6 to
omega-3 fatty acids because they lack the converting enzyme, omega3 desaturase. These two classes of essential fatty acids (EFAs) are not
interconvertible, are metabolically and functionally distinct and have
opposing physiological functions. Therefore, too much omega-6 may
be detrimental for cells. Corn oil is not a good source for EFAs because
the ratio of omega-6/omega-3 fatty acids from corn oil is 83, which is
much higher than the recommended ratio (1/1 to 4/1) (Simopoulos,
2002). However, the present study and other studies show that high
corn oil intake improves health and longevity in mice and rats
(10 mg/kg/d by oral gavage) (NTP, 1994). One explanation is that majority of omega-6 PUFA from corn oil is used for energy, and is not
used to produce thrombi and atheromas, which are required for cardiovascular disease development. Moreover, high levels of vitamin E (majorly -tocopherol) (Elmadfa and Park, 1999) and plant sterols (0.77% by
weight) (Ostlund et al., 2002) may counter the bad effects of omega-6
PUFA of corn oil. For example, -tocopherol, the major form of vitamin
E in the corn oil, and its metabolite have more anti-inammatory properties than -tocopherol, the predominant form of vitamin E in the tissues
and most supplements (Jiang and Ames, 2003).
Taken together, if total calorie intake is kept in a normal range,
long-term very high intake of corn oil (58.6% FDC) reverses agingincreased blood lipids and circulating pro-inammatory cytokines as
well as aging-damaged rotarod performance test and liver function,
and thus increases longevity of aging mice. These health benets of
corn oil may result from the combinations of the high levels of PUFA,

264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306

262
263

260
261

258
259

256
257

N
C
O

254
255

252
253

vitamin E and plant sterols. Therefore, corn oil, even at a high energy 307
percentage (58%), is a favorable replacement of animal fats in the 308
human diet if the total energy intake is controlled.
309

251

Conict of Interest

310

Values are means SE (n = 1214 per group).

P b 0.05.

The authors declare that there are no conicts of interest associated 311
with this manuscript.
312
Acknowledgments

313

We are grateful for the support of the National Institute of Food and 314
Agriculture of USDA, Evans-Allen program (TENX-1103-FS, to H. Si) for 315
this work.
316

t3:7
t3:8

R
O

YC
N
HF

t3:4
t3:5
t3:6

t3:3

References

317

Ahrens Jr., E.H., Insull Jr., W., Blomstrand, R., Hirsch, J., Tsaltas, T.T., Peterson, M.L., 1957.
The inuence of dietary fats on serum-lipid levels in man. Lancet 272, 943953.
Baur, J.A., Pearson, K.J., Price, N.L., Jamieson, H.A., Lerin, C., Kalra, A., Prabhu, V.V., Allard, J.S.,
Lopez-Lluch, G., Lewis, K., Pistell, P.J., Poosala, S., Becker, K.G., Boss, O., Gwinn, D.,
Wang, M., Ramaswamy, S., Fishbein, K.W., Spencer, R.G., Lakatta, E.G., Le Couteur, D.,
Shaw, R.J., Navas, P., Puigserver, P., Ingram, D.K., de Cabo, R., Sinclair, D.A., 2006. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444, 337342.
Brod, S.A., 2000. Unregulated inammation shortens human functional longevity.
Inamm. Res. 49, 561570.
Chance, B., Sies, H., Boveris, A., 1979. Hydroperoxide metabolism in mammalian organs.
Physiol. Rev. 59, 527605.
Chang, T.S., Cho, C.S., Park, S., Yu, S., Kang, S.W., Rhee, S.G., 2004. Peroxiredoxin III, a
mitochondrion-specic peroxidase, regulates apoptotic signaling by mitochondria.
J. Biol. Chem. 279, 4197541984.
Chung, H.Y., Sung, B., Jung, K.J., Zou, Y., Yu, B.P., 2006. The molecular inammatory process
in aging. Antioxid. Redox Signal. 8, 572581.
Coyle, C.A., Strand, S.C., Good, D.J., 2008. Reduced activity without hyperphagia contributes to obesity in Tubby mutant mice. Physiol. Behav. 95, 168175.
Dupont, J., White, P.J., Carpenter, M.P., Schaefer, E.J., Meydani, S.N., Elson, C.E., Woods, M.,
Gorbach, S.L., 1990. Food uses and health effects of corn oil. J. Am. Coll. Nutr. 9,
438470.
Elmadfa, I., Park, E., 1999. Impact of diets with corn oil or olive/sunower oils on DNA
damage in healthy young men. Eur. J. Nutr. 38, 286292.
Ferrucci, L., Corsi, A., Lauretani, F., Bandinelli, S., Bartali, B., Taub, D.D., Guralnik, J.M.,
Longo, D.L., 2005. The origins of age-related proinammatory state. Blood 105,
22942299.
Frisard, M., Ravussin, E., 2006. Energy metabolism and oxidative stress: impact on the
metabolic syndrome and the aging process. Endocrine 29, 2732.
Harman, D., 1972. The biologic clock: the mitochondria? J. Am. Geriatr. Soc. 20, 145147.
Heininger, K., 2000a. A unifying hypothesis of Alzheimer's disease. III. Risk factors. Hum.
Psychopharmacol. 15, 170.
Heininger, K., 2000b. A unifying hypothesis of Alzheimer's disease. IV. Causation and sequence of events. Rev. Neurosci. 213328 (11 Spec No).
Hill, P., Reddy, B.S., Wynder, E.L., 1979. Effect of unsaturated fats and cholesterol on serum
and fecal lipids. A study of healthy middle-aged men. J. Am. Diet. Assoc. 75, 414420.
Howell, T.J., MacDougall, D.E., Jones, P.J., 1998. Phytosterols partially explain differences in
cholesterol metabolism caused by corn or olive oil feeding. J. Lipid Res. 39, 892900.
Jiang, Q., Ames, B.N., 2003. Gamma-tocopherol, but not alpha-tocopherol, decreases proinammatory eicosanoids and inammation damage in rats. FASEB J. 17, 816822.
Labinskyy, N., Csiszar, A., Veress, G., Stef, G., Pacher, P., Oroszi, G., Wu, J., Ungvari, Z., 2006.
Vascular dysfunction in aging: potential effects of resveratrol, an anti-inammatory
phytoestrogen. Curr. Med. Chem. 13, 989996.
Landers, R., Rathmann, D., 1981. Vegetable oils: effects of processing, storage and use on
nutritional values. J. Am. Oil Chem. Soc. 58, 255259.
Linnane, A.W., Marzuki, S., Ozawa, T., Tanaka, M., 1989. Mitochondrial DNA mutations as
an important contributor to ageing and degenerative diseases. Lancet 1, 642645.
NCEP, 2002. Third Report of the National Cholesterol Education Program (NCEP) Expert
Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults
(Adult Treatment Panel III) Final Report. Circulation 106, 31433421.

318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366

t3:1
t3:2

Please cite this article as: Si, H., et al., High corn oil dietary intake improves health and longevity of aging mice, Exp. Gerontol. (2014), http://
dx.doi.org/10.1016/j.exger.2014.09.001

367
368
369
370
371
372
373
374
375
376
377
378
379
380

H. Si et al. / Experimental Gerontology xxx (2014) xxxxxx

NTP, 1994. NTP comparative toxicology studies of corn oil, safower oil, and tricaprylin
(CAS nos. 8001-30-7, 8001-23-8, and 538-23-8) in male F344/N rats as vehicles for
gavage. Natl. Toxicol. Program Tech. Rep. Ser. 426, 1314.
Ostlund, R.E., Racette, S.B., Okeke, A., Stenson, W.F., 2002. Phytosterols that are naturally
present in commercial corn oil signicantly reduce cholesterol absorption in humans.
Am. J. Clin. Nutr. 75, 10001004.
Reeves, P.G., Nielsen, F.H., Fahey Jr., G.C., 1993. AIN-93 puried diets for laboratory
rodents: nal report of the American Institute of Nutrition ad hoc writing committee
on the reformulation of the AIN-76A rodent diet. J. Nutr. 123, 19391951.
Si, H., Fu, Z., Babu, P.V., Zhen, W., Leroith, T., Meaney, M.P., Voelker, K.A., Jia, Z., Grange, R.W.,
Liu, D., 2011. Dietary epicatechin promotes survival of obese diabetic mice and Drosophila
melanogaster. J. Nutr. 141, 10951100.
Simopoulos, A.P., 2002. The importance of the ratio of omega-6/omega-3 essential fatty
acids. Biomed. Pharmacother. 56, 365379.

Sung, Y.Y., Kim, D.S., Kim, H.K., 2014. Viola mandshurica ethanolic extract prevents highfat-diet-induced obesity in mice by activating AMP-activated protein kinase. Environ.
Toxicol. Pharmacol. 38, 4150.
USDA, 2014. Corn: market outlook. http://www.agweb.com/crops/corn/default.aspx
(accessed August 28, 2014).
Veenbergen, S., Smeets, R.L., Bennink, M.B., Arntz, O.J., Joosten, L.A., van den Berg, W.B.,
van de Loo, F.A., 2010. The natural soluble form of IL-18 receptor {beta} exacerbates
collagen-induced arthritis via modulation of T cell immune responses. Ann. Rheum.
Dis. 69, 276283.
Yankner, B.A., Lu, T., Loerch, P., 2008. The aging brain. Annu. Rev. Pathol. 3, 4166.
Zou, Y., Jung, K.J., Kim, J.W., Yu, B.P., Chung, H.Y., 2004. Alteration of soluble adhesion
molecules during aging and their modulation by calorie restriction. FASEB J. 18,
320322.

R
O

394

Please cite this article as: Si, H., et al., High corn oil dietary intake improves health and longevity of aging mice, Exp. Gerontol. (2014), http://
dx.doi.org/10.1016/j.exger.2014.09.001

381
382
383
384
385
386
387
388
389
390
391
392
393