A cross-sectional assessment of oxidative DNA damage and muscle strength among elderly people living in the community
Environ Health Prev Med
A cross-sectional assessment of oxidative DNA damage and muscle strength among elderly people living in the community
Basilua Andre Muzembo 0 1
Yasunori Nagano 0 1
Masamitsu Eitoku 0 1
Nlandu Roger Ngatu 0 1
Tomomi Matsui 0 1
Sabah Asif Bhatti 0 1
Ryoji Hirota 0 1
Kenji Ishida 0 1
Narufumi Suganuma 0 1
0 Y. Nagano K. Ishida Department of Orthopedics, Kochi Medical School, Kochi University , Kohasu, Oko-cho, Nangoku-shi, Kochi 783-8505 , Japan
1 B. A. Muzembo (&) M. Eitoku N. R. Ngatu T. Matsui S. A. Bhatti R. Hirota N. Suganuma Division of Social Medicine, Department of Environmental Medicine, Kochi Medical School, Kochi University , Kohasu, Oko-cho, Nangoku-shi, Kochi 783-8505 , Japan
Objectives The mechanism by which muscle weakness leads to an increased risk of death remains a subject of interest. In this context, the aim of this study is to assess the relationship between urinary 8-hydroxy-20-deoxyguanosine (8-OHdG) and muscle strength, and other risk factors contributing to poor muscle strength in older persons. Methods This was a cross-sectional study in which a total of 86 participants, both men and women, aged 65 years or above were screened for urinary 8-OHdG, and muscle strength as measured by handgrip strength. Results Handgrip strength was lower in participants who had history of acute or chronic disease. Urinary 8-OHdG level was negatively associated with muscle strength, and the association remained after adjusting for confounding factors. Conclusions Urinary 8-OHdG is associated with muscle strength. These findings may be clinically relevant as there is a possibility of controlling oxidative DNA damage by healthy behaviors related to lifestyle.
Oxidative stress; Handgrip strength; Cross-sectional study; Older persons; Lifestyle
Japan’s demographic is currently an issue of public health
concern. The aging population of individuals aged 65 years
and above is on the increase (23.3 % of the population in
], while there is a shortage of working population
who could potentially support dependent older persons in
their daily activities. In both developed and developing
countries, increasing longevity and its logical outcomes
(frailty, physical disability or chronic diseases) have led to
a social and economic burden for dependent older persons,
relatives, healthcare professionals, and/or governments [
This observation has motivated research in gerontology
A great number of acute and chronic age-related
diseases have an underlying mechanism of oxidative stress
]. It is widely accepted that oxidative stress may play a
pivotal role in aging, disease onset and progression, and
mortality among older persons [
]. Oxidative stress is
defined as an imbalance between pro-oxidants released and
antioxidant defenses in favor of pro-oxidants, which can
damage cell structures including proteins, lipids,
carbohydrates, and deoxyribonucleic acid (DNA), leading to health
]. Measurement of reactive oxygen species
(ROS) is difficult because their half-lives are usually very
short; therefore, evaluation of oxidative stress in biological
fluids is realized by quantification of oxidative stress
Several biomarkers of oxidative stress are known,
including 8-hydroxy-20-deoxyguanosine (8-OHdG). The
biomarker 8-OHdG is the oxidized form of nucleoside in
DNA; it is the most representative and detected product of
oxidative DNA damage excreted in urine upon DNA
]. In humans, urinary 8-OHdG has been
associated with various health conditions including cancer, heart
failure, and diabetes [
]. Higher levels of 8-OHdG have
also been found in biopsied skeletal muscle of older
persons and probably contribute to age-dependent poor muscle
strength. ROS have been known to play an important role
in the aging process of human skeletal muscle [
Poor skeletal muscle strength is both a common
condition and serious health problem among older persons, even
those who are healthy. For humans, skeletal muscle
weakness appears to be unavoidable with aging, starting from the
fourth or fifth decade of life, leading to a decline in physical
function, frailty [
] or dependency . Moreover, in
old age, muscle weakness has been linked with several poor
outcomes including increased risk of falling [
disabilities and death [
10, 13, 14
]. In this regard, controlling
oxidative stress through healthy behaviors related to lifestyle
(such as physical activities, smoking cessation) and
nutritional factors (diet-derived antioxidants) is thought to be
vital in promoting geriatric health.
The mechanism by which poor skeletal muscle strength
leads to poor outcomes remains a subject of interest in the
biology of aging. Studies regarding urinary 8-OHdG and
muscle strength among older persons are scarce. The
purpose of this study is to examine whether urinary 8-OHdG is
associated with muscle strength in a group of older persons
living in the community.
Subjects and methods
Study design and recruitment
The present study was approved by the Research Ethics
Committee of Kochi Medical School, and was carried out
in accordance with the Declaration of Helsinki. Informed
consent was obtained from all participants in written form.
This was a cross-sectional study designed to assess the
health status of older persons living in one of the cities in
Kochi Prefecture, Japan, for a healthy aging goal.
Participation was on a voluntary basis; postal invitations
containing an explanation of the purpose of the study and the
health check-up schedule were mailed by the local welfare
committee to 1103 potential participants, who were
targeted based on the following inclusion criteria: being aged
65 years or above, and being able to answer a survey
questionnaire. Of the 1103 postal invitations sent to
potential participants, a total of 100 older persons attended
local community centers for medical examination.
Health assessment and measurements
The participants were assessed for lifestyle, past medical
history, functional status, and anthropometric
measurements. Information gathered on their lifestyle included
physical activities, smoking habits, alcohol consumption,
social life, and dietary habits. The medical history-taking
emphasized past chronic disease, acute disease within the
last 3 months, and current medication.
Functional status was evaluated using activities of daily
living (ADL) [
] and instrumental activities of daily
living (IADL) [
]. Anthropometric parameters evaluated
were height, weight, and body mass index (BMI). The
participants’ height was measured using a stadiometer, and
body weight using a mechanical medical scale. BMI was
calculated by dividing weight in kg by height in meters
squared, and was categorized based on guidelines of the
National Heart, Lung, and Blood Institute [
In addition, blood pressure was measured. Blood
pressure (BP) was evaluated with a mercury
sphygmomanometer after the participants had had a 10-min rest. Blood
pressure was classified into the following four categories
according to the seventh report of the Joint National
Committee on Prevention, Detection, Evaluation, and
Treatment of High Blood Pressure [
]: normal (systolic
BP \120 mmHg and diastolic BP \80 mmHg),
prehypertension (systolic BP = 120–139 mmHg or diastolic
BP = 80–89 mmHg), hypertension stage I (systolic
BP = 140–159 mmHg or diastolic BP = 90–99 mmHg),
and hypertension stage II (systolic BP C160 mmHg or
diastolic BP C100 mmHg).
Muscle strength evaluation
Handgrip strength was used for muscle strength testing.
Handgrip strength measurements were assessed using a
handled dynamometer (T.K.K. 5401 GRIP-D; Takei
Scientific Instruments Co. Ltd., Tokyo, Japan) with each
participant in standing position and being encouraged to
exert maximum force during the test. The measurement
was performed in both hands and was expressed in
kilograms. Three trials were performed for each handgrip
strength measurement in each hand, and then the mean of
both hands was used for analysis. Prior to the handgrip test,
participants’ blood pressure was measured to exclude those
with blood pressure of 180/110 mmHg and above.
The cut-off values for handgrip strength (\30 kg for
men and \20 kg for women) recommended by the
European Working Group on Sarcopenia in Older People
(EWGSOP) to recognize a person with mobility limitation
were used as a reference [
Biological assays included levels of 8-OHdG and
creatinine. Spot urine samples were collected using paper cups.
The samples were centrifuged at 2000 rpm for 5 min, and
stored at -80 C until measurements.
Urinary 8-OHdG levels (new 8-OHdG Check; the Japan
Institute for the Control of Aging, Fukuroi, Japan) were
determined using enzyme-linked immunosorbent assay
kits, and were adjusted with creatinine and expressed in ng/
mg creatinine. Urinary creatinine was measured by a
method based on the reaction of creatinine and alkaline
picrate in conformity with the manufacturer’s instructions
(creatinine test kit; R&D Systems, Minneapolis, MN).
There were 86 participants who had both urinary
8-OHdG levels and muscle strength data measurements
available for analysis.
The results of quantitative variables are summarized as
mean ± standard deviation of the mean, or as frequency
and percentage. The chi-squared test and Student’s t test
were used to assess differences in categorical and
continuous variables, respectively. The correlation between
urinary 8-OHdG and muscle strength was examined using
Pearson’s correlation test. Multiple regression analysis was
performed to evaluate the relationship between muscle
strength and urinary 8-OHdG, and other studied
parameters. Data were analyzed using the Stata software package
version 10 (StataCorp LP; TX 77845, USA), and p \ 0.05
was regarded as significant.
As shown in Table 1, out of the 86 participants, 68 (79 %)
were women. The average age of the participants was
76.5 years. Compared with women, men were significantly
older (78.9 versus 75.8 years; p = 0.027) and had
significantly higher weight (57.4 versus 48.8 kg; p \ 0.001);
however, men and women had similar BMI (23.2 versus
22.4 kg/m2). The mean blood pressure was 136/71 mmHg;
the minimum value of systolic blood pressure was
90 mmHg and the maximum was 178 mmHg, while the
minimum value of diastolic blood pressure was 61 mmHg
and the maximum 90 mmHg. Thirty-seven (43 %)
participants had pre-hypertension, 26 (30.2 %) hypertension
stage I, and 14 (16.2 %) hypertension stage II. The chronic
diseases most reported were hypertension (37.6 %),
diabetes mellitus (19.0 %), arthritis (13.0 %), and coronary
heart disease (4.7 %). Comorbidity was found in 12
(13.9 %) participants, whereas 36 (41.8 %) did not report
any history of chronic disease.
The evaluation of ADL items revealed that 19 (22.0 %)
of the 86 participants had dependence in at least one ADL
item while 25 (29.0 %) participants had limitation in at
least one IADL item. Shopping and house-keeping were
the tasks reported as most difficult by participants. Only a
few participants declared a loss of interest in social life: 8
(9.3 %) were not visiting any friend or relative, while 12
(14.1 %) were not attending any social events.
Findings in urine and muscle strength testing
The mean values of urinary 8-OHdG level and muscle
strength are presented in Table 2. The average urinary
8-OHdG level was 10.1 ± 4.8 ng/mg creatinine, and did
not differ between men and women. Participants who
‘‘occasionally’’ consumed alcohol had significantly lower
urinary 8-OHdG level (7.9 ± 2.7 ng/mg creatinine) than
those who did not consume alcohol (10.4 ± 5.0 ng/mg
creatinine, p = 0.022) or those who consumed alcohol
daily (10.4 ± 4.7 ng/mg creatinine, p = 0.016).
The mean handgrip strength was 30.4 kg for men and
20.4 kg for women; seven (38.8 %) men had handgrip
strength lower than 30 kg, and 27 (39.7 %) women had
handgrip strength lower than 20 kg, meaning that in this
study 34 (39.5 %) participants had poor handgrip strength.
In both sexes, levels of 8-OHdG were significantly higher
in participants with poor handgrip strength compared with
those with normal handgrip strength (Table 3).
The mean handgrip strength did not differ between right
and left hands, or between nonsmokers and ex-smokers.
The mean handgrip strength was significantly higher
(p = 0.033) in participants in the group ranging between 65
and 74 years (24.2 ± 7.3 kg) compared with those who
were over 75 years of age (21.5 ± 5.8 kg). When muscle
strength was analyzed in relation to the history of acute
disease during the last 3 months, we found that muscle
strength was significantly lower in participants who had
history of acute disease compared with those without
(18.8 ± 9.0 versus 23.0 ± 6.2 kg, p = 0.035). Conversely,
when muscle strength was assessed in regard to chronic
diseases, we found that muscle strength decreased with the
presence of chronic diseases (21.6 ± 6.1 versus
23.6 ± 7.0 kg, p = 0.083). Moreover, comparing
participants who engaged in regular physical exercise versus those
who did not, the former had significantly higher handgrip
strength (21.0 ± 5.5 versus 24.0 ± 7.0, p = 0.017).
Correlation of muscle strength with urinary 8-OHdG
and other health parameters
The correlation between handgrip strength and urinary
8-OHdG, and other health factors, is presented in Table 4.
A negative correlation was noted between handgrip
strength and urinary 8-OHdG (r = -0.318; p = 0.002);
handgrip strength was correlated negatively with history of
acute disease in the last 3 months in women, a correlation
Men (n = 18)
10.0 ± 5.7
31.1 ± 8.4
29.8 ± 8.1
30.4 ± 8.0
Men n (%)
Women n (%)
8-Hydroxy-20-deoxyguanosine (ng/mg cr.)
8-Hydroxy-20-deoxyguanosine (ng/mg cr.)
The cut-off values for poor handgrip strength are \30 kg for males and \20 kg for females
* p \ 0.05 (by Student’s t-test)
not seen in men. Handgrip strength was negatively
correlated with age in men, but not in women. In the combined
group of all participants, handgrip strength was positively
correlated with physical exercise, weight, and BMI.
Regression analysis for handgrip strength
The result of the univariate linear regression analysis in
predicting low handgrip strength showed that having higher
urinary 8-OHdG levels was significantly associated with
low handgrip strength (Figs. 1, 2). Table 5 presents the
results of multivariate linear regression analysis of the
association between handgrip strength and urinary 8-OHdG
levels in all participants. The first model used age, gender,
weight, BMI, and urinary 8-OHdG levels as predictors.
After adjusting for these factors, urinary 8-OHdG levels
were significantly associated with handgrip strength;
Urinary 8-OHdG levels, age, gender and weight accounted for
64 % of the variation of handgrip strength. This association
remained significant in the second model after controlling
for age, sex, weight, BMI, physical exercise, alcohol
consumption, and diseases. This model showed that urinary
8-OHdG levels, age, gender, weight and acute disease
explained about 65 % of the variance of handgrip strength.
In the present study, we investigated the relationship
between a biomarker of oxidative DNA damage and
muscle strength, and other risk factors contributing to poor
muscle strength such as disease and sedentary lifestyle, in a
group of older persons living freely in the community.
Urinary 8-OHdG and handgrip strength
8-OHdG is an in vivo biomarker of oxidative DNA damage
considered to be useful in predicting the risk of
lifestylerelated disease [
]. In living cells, ROS are produced
incessantly as by-products of biological reactions. ROS in
moderate concentrations are essential signaling molecules
that regulate physiological processes such as defense
against infectious agents; however, ROS interact with
lipids, proteins, and DNA, resulting in oxidative stress [
Fig. 1 Scatter diagram of
handgrip strength and urinary
levels in women (n = 68); this
figure suggests that handgrip
strength of women decreases as
8-hydroxy-20deoxyguanosine level increases
Fig. 2 Scatter diagram of
handgrip strength and urinary
levels in men (n = 18); this
figure shows that handgrip
strength of men decreases as the
8-hydroxy-20deoxyguanosine level increases
Physiologically, there is a balance between ROS
production and antioxidant defenses, enzymatic or nonenzymatic.
In case of imbalance, ROS induce DNA lesions which play
a crucial role in the initiation and promotion of cancer,
aging, and other degenerative diseases [
]. In this study,
urinary 8-OHdG was selected to assess levels of oxidative
DNA damage because urinary 8-OHdG is considered to be
the most representative and reliable biomarker of DNA
injury induced by ROS [
]. The mean levels of urinary
8-OHdG in this study (10.1 ± 4.8 ng/mg creatinine) are
similar to the value in normal human urine (8.4 ng/mg
creatinine) reported by the Japan Institute for the Control of
Aging (JaICA 2012) [
]. However, this value is
significantly lower compared with the value reported by a
previous study dealing with Japanese older persons living in
temporary houses after natural disasters (12.1 ± 6.8 ng/mg
creatinine, n = 73) [
Handgrip strength was used for the measurement of
muscle strength. We decided to use handgrip strength
because it is recommended by the EWGSOP [
muscle strength assessment, and also because, apart from
the handgrip test being easy, reliable, and relatively low
cost, screening for handgrip can help to identify older
persons with high risk of health impairment [
cutoff values for handgrip strength recommended by the
EWGSOP to diagnose a person with low muscle strength
are \30 kg for men and \20 kg for women [
]. In the
present study, the mean values of handgrip strength
(30.4 kg for men and 20.4 kg for women) were above the
mentioned thresholds. However, it should be mentioned
that 39.5 % of the participants had low handgrip strength
with high levels of urinary 8-OHdG, showing that urinary
8-OHdG may be a potential marker useful in predicting the
risk of poor muscle strength in older persons. Therefore,
early interventions to increase muscle strength are required
for these participants with low handgrip strength to
possibly improve their health.
The major findings of this study are that urinary
8-OHdG level was negatively associated with muscle
strength, and that this association remained even after
adjusting for confounding factors; these findings are
supported by the mechanism whereby progressive
mitochondrial oxidative DNA damage reduces muscle mitochondrial
protein synthesis, which leads to poor muscle strength [
]. Increased inflammatory markers such as C-reactive
protein and interleukin-6 have been shown to be associated
with poor physical performance and muscle strength in
older persons [
]. In addition, Schaap et al. [
demonstrated that high levels of tumor necrosis factor-a were
associated with a decline in grip strength. Taken together
with the inverse association observed between urinary
8-OHdG levels and grip strength in this study, these results
may raise awareness in routine clinical practice, and
perhaps be an attractive target for clinical trials involving poor
grip strength. However, it is important to note that neither
urinary 8-OHdG nor the inflammatory markers (tumor
necrosis factor-a, C-reactive protein, and interleukin-6) are
muscle specific [
Our findings are in line with previous studies that
demonstrated an inverse association between oxidative stress
and muscle strength [
]. One study demonstrated that
Chinese frail older persons had higher serum 8-OHdG
levels than nonfrail older persons [
]. Another study found
that high levels of serum reactive oxygen metabolites were
inversely correlated with handgrip strength in Mongolians
(20–70 years old) having higher levels of urinary 8-OHdG
]. In addition, an association between oxidative stress
and muscle strength among older women living in
Baltimore, USA was previously described [
]. The latter study
found that high serum protein carbonyl (a biomarker of
protein oxidation) was independently associated with poor
muscle strength, as measured by handgrip strength, among
672 older women living in the community. While our
findings are consistent with these studies, there are primary
differences that deserve a mention: the study conducted in
Baltimore included both moderately and severely disabled
older women, while only 14 % of the participants were
nonfrail in the study conducted in China. The fact that these
older persons were disabled or frail might have exposed
them to high levels of oxidative stress, as higher levels of
oxidative stress had been reported in older persons with
physical disability [
]. In contrast to these two studies, our
study included older persons without physical disability,
79 % of whom were women.
Disease and handgrip strength
Disability in older persons, either catastrophic or
progressive, is a logical outcome of disease [
], with an
underlying mechanism of oxidative stress [
]. A study by
Cappola et al. [
] reported that diseases in association
with poor nutrition and sedentary lifestyle reduce
insulinlike growth factor (IGF-1) production, which leads to poor
muscle strength. Muscle fatigability, in association with
chronic diseases, leads to poor mobility, and therefore to
frailty. In accordance with this fact, our findings revealed
that about 57.6 % of the participants reported suffering
from at least one chronic disease and 12.2 % had an acute
disease in the last 3 months. Muscle strength was lower in
participants with history of acute or chronic disease
compared with those without. Our observation corroborates
a previous 27-year follow-up study which demonstrated
that chronic diseases were responsible for the rapid decline
of muscle strength among men with Japanese ancestors
]. However, the sexes in these studies are different, as
ours included both men and women. In addition, this study
does not allow us to affirm whether low grip strength was a
consequence or a cause of disease process, because of its
cross-sectional design. Disease leads to muscle fatigability
directly or through sedentary lifestyle [
Physical exercise and handgrip strength
Studies about sedentary lifestyle or physical activities and
muscle strength are controversial; as expected, in this
study, the 48 (55.8 %) participants engaging in regular
physical activity were found to have greater handgrip
strength. Our findings are consistent with a 5-year
followup study which showed that physical exercise in elderly
people helps to maintain muscle strength [
inconsistent with a 10-year follow-up study which found no
association between physical activity and muscle strength
]. Another 22-year follow-up study did not find the
expected benefits of regular physical activity, but only a
decrease in muscle strength in participants who became
physically inactive during follow-up [
The participants in this study were likely to be
healthoriented elderly people in relatively good health, even if
some of them had chronic diseases. We do not know if the
association observed between 8-OHdG and muscle strength
will still hold in a population under the age of sixty. The
participants in this study may not be completely
representative of the older persons in the town; it should be
mentioned that the response rate following the postal
invitation was very low (9 %). According to the local
welfare committee, the main reasons for the low response
could be due to the participants’ work schedules. Other
reasons for nonparticipation may have been health related,
such as lack of confidence in being healthy, walking
disability, the fact that they are already going to hospital
regularly, or an absence of disease among mobile older
persons that could have led to a lack of interest in the
medical check-up. Carrying out the medical check-up in
the participant’s home needs to be considered when
planning future studies in this town.
In conclusion, the main finding of this study is that
urinary 8-OHdG is independently associated with muscle
strength. This finding may be clinically relevant as there is
a possibility of controlling oxidative DNA damage by
healthy behaviors related to lifestyle such as cigarette
smoking cessation, regular physical exercise, and low-fat
diet or calorie restriction.
Acknowledgments This work was financially supported by funding
from Kochi University and city office of Kuroshio town, Kochi
prefecture, Japan. The authors wish to thank the elderly people who
participated in this study. They are also grateful to Mr. Daniel Ribble,
Mr Mugo Andrew, and Ms Mansongi Biyela Carine for their advice
on the manuscript.
Conflict of interest There are no conflicts of interest regarding the
content of this study.
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