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Age-Related Changes of Elements

in Human Ureter
YASUO TAKANO,1 YOSHIYUKI TOHNO,*,2 YUMI MORIWAKE,2
SETSUKO TOHNO,2 TAKESHI MINAMI,2 MASA-OKI YAMADA,2
AND KAZUNARI YURI1
1
Department of Anatomy, Kochi Medical School, Nangoku,
Kochi 783-8505, Japan; and 2Laboratory of Cell Biology,
Department of Anatomy, Nara Medical University,
Kashihara, Nara 634-8521, Japan
Received May 27, 1999; Accepted June 19, 1999

ABSTRACT
To elucidate changes of the ureter with aging, the authors inves-
tigated age-related changes of element contents in human ureters. The
subjects consisted of seven men and seven women, ranging in age
from 61 to 97 yr. The contents of calcium, sulfur, and iron in the
ureters increased progressively with aging, whereas the contents of
phosphorus and magnesium did not increase with aging. Significant
relationships were found both between calcium and sulfur contents
and between calcium and iron contents in the ureters, but not
between calcium and either phosphorus or magnesium contents. It
was noteworthy that a significant relationship was also found be-
tween sulfur and iron contents in the ureters. It remains uncertain
whether calcium forms a compound with sulfur or iron in aged human
ureters or not.
Index Entries: Ureter; calcium; sulfur; iron; aging.

INTRODUCTION
To elucidate changes of human tissues during the aging process, the
authors have studied age-related changes of element contents in various
tissues by inductively coupled plasma–atomic emission spectrometry.
Age-related changes of mineral contents in the blood vessels of arteries

*Author to whom all correspondence and reprint requests should be addressed.

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118 Takano et al.

(1–4) and veins (5), in the cardiac valves (6), in the bones (7–10), in the car-
tilages (11–14), and in the ligaments (15) were previously reported by us.
There are several reports (16–23) with regard to age-related changes
of the ureter. The morphometric study (19) revealed that the muscle layer
of guinea pig ureters increased with aging. Biochemical investigations
demonstrated that cAMP levels, adenylyl cyclase activity, and the sub-
sequent relaxation response to the β-adrenergic agonist, decreased with
aging in the guinea pig ureter (20), whereas soluble guanylyl cyclase
activity increased with aging (21).
The authors studied age-related changes of element contents in
human ureters and found that the contents of calcium, sulfur, and iron in
the human ureter increased progressively during the aging process, and
significant relationships were found both between calcium and sulfur con-
tents and between calcium and iron contents. It was noteworthy that there
was also a positive relationship between sulfur and iron contents.

MATERIALS AND METHODS

Sampling of the Ureters

Cadavers were treated by injection of a mixture of 63% ethanol, 21%
ethylene glycol, 14% formalin, and 1% cell conditioner (Champion Prod-
uct, Springfield, OH, USA). After the ordinary dissection by medical stu-
dents was finished, ureters were resected about 3 cm in length at the
height of about 5 cm below the renal hilus from 14 subjects, ranging in
age from 61 to 97 yr, and they were washed with distilled water.

Determination of Elements
The samples of ureters were dried at 80°C for 16 h. After the addi-
tion of 1 mL nitric acid, they were heated for 2 h at 100°C in a dry block
bath (EB-303, Iuchi, Osaka, Japan). After the addition of 0.5 mL perchloric
acid, they were heated for a further 2 h at 100°C. The samples were ad-
justed to a volume of 10 mL by adding ultrapure water (Milli-Q Jr., Mil-
lipore, Tokyo, Japan) and filtered through the filter paper with a pore size
of 4 µm (No. 7, Toyo Roshi, Osaka, Japan). The resulting filtrates were
analyzed with an inductively coupled plasma–atomic emission specrom-
eter (ICPS-1000 III, Shimadzu, Kyoto, Japan). The conditions were 1.2 kW
of power from a radio-frequency generator, a plasma argon flow rate of
1.2 L/min, a cooling gas flow of 14 L/min, a carrier gas flow of 1.0 L/
min, a 20-µm entrance slit, a 30-µm exit slit, 15 mm at the height of obser-
vation, and an integration time lapse of 5 s.

Statistical Analysis
Statistical analyses were performed by using GraphPad Prism Version
2.0 (GraphPad Software, Inc., San Diego, CA, USA). Data were expressed

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Elements in Human Ureter 119

Table 1
Element Contents of the Ureters

Note: M and W indicate man and woman, respectively.

as the mean ± standard deviation (SD). The amount of the element was
expressed on a dry-weight basis.

RESULTS

Contents of Elements in Human Ureters

The subjects consisted of seven men and seven women, ranging in age
from 61 to 97 yr. Table 1 lists the element contents in the human ureters.
Predominant elements were sulfur, phosphorus, calcium, and sodium.
Moderate ones were magnesium and iron, and silicon and zinc were a
trace. The average contents were 3.00 ± 0.72 mg/g of sulfur, 3.25 ± 2.76
mg/g of phosphorus, 1.04 ± 0.43 mg/g of calcium, and 1.02 ± 0.42 mg/g
of sodium. High contents of phosphorus and magnesium were detected in
one case of the ureter from the subject which died of septicemia.

Age-Related Changes of Elements

in Human Ureters
Figure 1 shows a relationship between age and sulfur content in
the human ureters. The correlation coefficient was estimated to be 0.566
(p-value = 0.035). A high correlation was found between age and sulfur
content. The average content of sulfur in the eighties was 24% higher
than that in the sixties.
A relationship between age and calcium content is shown in Fig. 2.
The correlation coefficient was estimated to be 0.731 (p-value = 0.003).
There was a very high correlation between age and calcium content. The
average content of calcium in the eighties was about 1.5-fold the amount
of that in the sixties or seventies.

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120 Takano et al.

Fig. 1. Age-related change of sulfur contents in the ureters. The open

and filled circles indicate sulfur contents in the men’s and women’s ureters,
respectively.

Fig. 2. Age-related change of calcium contents in the ureters. The open

and filled circles indicate calcium contents in the men’s and women’s ureters,
respectively.

Figure 3 shows a relationship between age and iron content. The

correlation coefficient was estimated to be 0.702 (p-value = 0.005). A
high correlation was found between age and iron content. The average
content of iron in the eighties was about three-fold the amount of that
in the sixties.
In contrast, there were no correlations between age and the other
element contents, such as phosphorus and magnesium, because the

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Elements in Human Ureter 121

Fig. 3. Age-related change of iron contents in the ureters. The open and
filled circles indicate iron contents in the men’s and women’s ureters, respectively.

Fig. 4. Relationship between calcium and sulfur contents in the ureters.

correlation coefficients were −0.168 (p-value = 0.566) in phosphorus and

−0.170 (p-value = 0.562) in magnesium.

Correlations Among Element Contents

in Human Ureters
A relationship between calcium and sulfur contents is shown in Fig. 4.
The correlation coefficient was estimated to be 0.578 (p-value = 0.031).
There was a moderate correlation between calcium and sulfur contents.

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122 Takano et al.

Fig. 5. Relationship between calcium and iron contents in the ureters.

Fig. 6. Relationship between sulfur and iron contents in the ureters.

As the calcium content increased, the sulfur content increased in the

ureters.
Figure 5 shows a relationship between calcium and iron contents. The
correlation coefficient was estimated to be 0.751 (p-value = 0.002). A high
correlation was found between calcium and iron contents. As the calcium
content increased, the iron content increased in the ureters. In contrast,
there were no correlations between calcium and the other element con-
tents, such as phosphorus, magnesium, and sodium, because the cor-
relation coefficients were −0.026 (p-value = 0.929) in phosphorus, 0.045
(p-value = 0.878) in magnesium, and 0.017 (p-value = 0.955) in sodium.

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Elements in Human Ureter 123

A relationship between sulfur and iron contents is shown in Fig. 6.

The correlation coefficient was estimated to be 0.732 (p-value = 0.003). A
high correlation was found between sulfur and iron contents.

DISCUSSION
The present study revealed that the contents of calcium, sulfur, and
iron increased progressively with aging.
There are some reports regarding age-related changes of ureters
(16–23). Akimoto et al. (16) studied the diametral and longitudinal defor-
mations of the in vitro rabbit ureters in response to the applied intra-
luminal pressure load and reported that the deformation was more
marked in the neonate than in the adult. Ureteral diameters were esti-
mated by intravenous urography (17) and autopsy (18) in children, and
it was revealed that they increased progressively with aging. Hong et al.
(19) investigated the effects of age on contractility of guinea pig ureters
and found that the muscle layer of the ureter increased with age, with
very high correlation coefficients for distal and proximal segments of
the ureter.
Biochemical investigations of Wheeler et al. (20) demonstrated that
the cAMP level, adenylyl cyclase activity, and the subsequent relaxation
response to the β-adrenergic agonist isoproterenol decreased with aging
in the guinea pig ureter. They (21) also reported that when the ureter of
the young guinea pig was compared to that from the old adult guinea
pig, the relaxation response to sodium nitropruside, which increased
cGMP levels by activating soluble guanylyl cyclase, increased 27–48%
with aging.
The authors reported previously that calcium contents increased
with aging in most but not all of the arteries (1–4), in cartilages such as
the intervertebral disk (11), pubic symphysis (12), meniscus (13), articu-
lar disk of temporomandibular joint (14), in ligaments (15) such as the an-
terior cruciate ligament and the ligament of head of femur, and in
the Achilles tendon, whereas they decreased reversely with aging in the
spongy bones, such as the calcaneus (8), talus, and scaphoid bone.
It is established that calcification occurs in both aged arteries (3,4)
and aged cartilages (11–14), in which significant correlations are found
between calcium and phosphorus contents. However, no correlation was
found between calcium and phosphorus contents in the ureters. There-
fore, it is unlikely that calcification occurs in aged ureters.
Regarding sulfur, the content hardly changed during the aging
process in all of the tissues examined previously (1–15). Interestingly, the
sulfur content of the ureters increased with aging. In addition, the iron
content of the ureters increased progressively with aging. It is known
that there are proteins with both iron and sulfur (Fe/S proteins) and they
are present in mitochondria or chloroplasts (24). As the contents of sulfur

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124 Takano et al.

and iron increase simultaneously with aging in the ureter, there is a pos-
sibility that Fe/S proteins such as cytochromes c increase in the aged
human ureter. However, it is not evident whether Fe/S proteins really
increase with aging in the ureter or not. Our results are compatible to the
finding of Wheeler et al. (21) that the soluble guanylyl cyclase activity
increases with aging in the guinea pig ureter, despite the guanylyl
cyclase without Fe and S.

REFERENCES
1. Y. Tohno, S. Tohno, T. Minami, M. Ichii, Y. Okazaki, M. Utsumi, et al., Age-related
changes of mineral contents in human thoracic aorta and in the cerebral artery, Biol.
Trace Element Res. 54, 23–31 (1996).
2. T. Araki and Y. Tohno, Age dependency of nanosecond fluorescence characteristics in
human artery, Front. Med. Biol. Eng. 7, 265–273 (1996).
3. S. Tohno and Y. Tohno, Age-related differences in calcium accumulation in human
arteries, Cell. Mol. Biol. 44, 1253–1263 (1998).
4. S. Tohno, M. Masuda, Y. Tohno, Y. Moriwake, T. Minami, M. Utsumi, et al., High
accumulation of calcium and phosphorus in human iliac arteries, Biol. Trace Element
Res. 70, 41–49 (1999).
5. S. Tohno, Y. Tohno, T. Minami, Y. Okazaki, M. Utsumi, F. Nishiwaki, et al., A high
accumulation of minerals in human internal jugular vein, Biol. Trace Element Res. 62,
17–23 (1998).
6. S. Tohno, Y. Moriwake, Y. Tohno, T. Minami, F. Nishiwaki, M. Utsumi, et al., Age-
related changes of element contents in human mitral and tricuspid valves, Biol. Trace
Element Res., 70, 137–147 (1999).
7. Y. Tohno, S. Tohno, M. Utsumi, T. Minami, M. Ichii, Y. Okazaki, et al., Age-independent
constancy of mineral contents in human vertebrae and auditory ossicles, Biol. Trace
Element Res. 59, 167–175 (1997).
8. Y. Tohno, M. Utsumi, S. Tohno, T. Minami, Y. Okazaki, Y. Moriwake, et al., Age-
dependent changes of mineral contents in man’s and woman’s calcanei, Biol. Trace
Element Res. 60, 81–90 (1997).
9. Y. Tohno, M. Utsumi, S. Tohno, T. Minami, Y. Okazaki, Y. Moriwake, et al., A con-
stancy of mineral contents in human auditory ossicles, Acta Anat. Nippon. 72, 531–534
(1997).
10. M. Utsumi, S. Tohno, T. Minami, Y. Okazaki, Y. Moriwake, M.-o. Yamada, et al., Age-
independent constancy of mineral contents in human ribs, Biol. Trace Element Res. 67,
165–171 (1999).
11. S. Tohno, Y. Tohno, T. Minami, M. Ichii, Y. Okazaki, M. Utsumi, et al., Difference of
mineral contents in human intervertebral disks and its age-related change, Biol. Trace
Element Res. 52, 117–124 (1996).
12. S. Tohno, Y. Tohno, T. Minami, Y. Okazaki, M. Utsumi, Y. Moriwake, et al., High accu-
mulations of calcium and phosphorus in woman’s pubic symphysis, Biol. Trace Ele-
ment Res. 59, 177–185 (1997).
13. Y. Moriwake, Y. Tohno, S. Tohno, T. Minami, M. Utsumi, F. Nishiwaki, et al., Age-
related changes of element contents in the human meniscus, Biol. Trace Element Res.
64, 229–235 (1998).
14. Y. Takano, Y. Moriwake, Y. Tohno, T. Minami, S. Tohno, M. Utsumi, et al., Age-related
changes of elements in the human articular disk of temporomandibular joint, Biol.
Trace Element Res. 67, 269–276 (1999).
15. Y. Tohno, Y. Moriwake, Y. Takano, T. Minami, S. Tohno, M. Utsumi, et al., Age-related
changes of elements in human anterior cruciate ligaments and ligamenta capitum
femorum, Biol. Trace Element Res. 68, 181–192 (1999).

Biological Trace Element Research Vol. 74, 2000

Elements in Human Ureter 125

16. M. Akimoto, P. Biancani, and R. M. Weiss, Comparative pressure–length–diameter

relationships of neonatal and adult rabbit ureters, Invest. Urol. 14, 297–300 (1977).
17. M. Akimoto, S. Okumura, and H. Kawai, Studies of the hydrodynamic changes
in the ureter—Morphological changes of the rabbit ureter following internal pres-
sure load and influence of aging and reserpine [in Japanese], Jap. J. Urol. Assoc. 68,
945–951 (1977).
18. L. J. Cussen, Dimensions of the normal ureter in infancy and childhood, Invest. Urol.
5, 164–178 (1967).
19. K. W. Hong, P. Biancani, and R. M. Weiss, Effect of age on contractility of guinea pig
ureter, Invest. Urol. 17, 459–461 (1980).
20. M. A. Wheeler, A. Housman, Y. H. Cho, and R. M. Weiss, Age dependence of
adenylate cyclase in guinea pig ureter homogenate, J. Pharmacol. Exp. Ther. 239,
99–103 (1986).
21. M. A. Wheeler, M. Pontari, S. Dokita, T. Nishimoto, Y. H. Cho, K. W. Hong, et al.,
Age-dependent changes in particulate and soluble guanylyl cyclase activities in uri-
nary tract smooth muscle, Mol. Cell. Biochem. 169, 115–124 (1997).
22. M. Yoshida, J. Latifpour, and R. M. Weiss, Age-related changes in calcium antagonist
receptors in rabbit ureter, Dev. Pharmacol. Ther. 18, 100–107 (1992).
23. M. A. Wheeler, Y. H. Cho, K. W. Hong, and R. M. Weiss, Age-dependent alterations
in beta-adrenergic receptor function in guinea pig ureter, in Frontiers in smooth mus-
cle research, N. Speralakis and G. Wood, ed., Wiley-Liss, New York, pp. 711–715 (1990).
24. J. J. R. Frausto da Silva and R. J. P. Williams, The Biological Chemistry of the Elements.
The Inorganic Chemistry of Life, Oxford, New York (1994).

Biological Trace Element Research Vol. 74, 2000