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1. Bauer JM, Sieber CC. Sarcopenia and frailty: A clinician’s controversial

point of view. Exp Gerontol 2008;43:674–678.2. Hubbard RE, O’Mahony MS, Calver BL et al. Nutrition, inflammation,

and leptin levels in aging and frailty. J Am Geriatr Soc 2008;56:279–284.3. Lakoski SG, Cushman M, Rundek T et al. Gender and C-reactive protein:

Data from the Multiethnic Study of Atherosclerosis (MESA) cohort. Am

Heart J 2006;152:593–598.4. Leng SX, Cappola AR, Andersen RE et al. Serum levels of insulin-like

growth factor-I (IGF-1) and dehydroepiandrosterone sulfate (DHEA-S),

and their relationships with serum interleukin-6, in the geriatric syndrome

of frailty. Aging Clin Exp Res 2004;16:153–157.5. Gatford KL, Egan AR, Clarke IJ et al. Sexual dimorphism of the somato-

trophic axis. J Endocrinol 1998;157:373–389.6. Dupre ME, Liu G, Gu D. Predictors of longevity: Evidence from the old-

est-old in China. Am J Public Health 2008;98:1203–1208.7. Avila-Funes JA, Helmer C, Amieva H et al. Frailty among community-

dwelling elderly people in France: The Three-City Study. J Gerontol A

Biol Sci Med Sci 2008;63A:1089–1096.8. Imahara SD, Jelacic S, Junker CE et al. The influence of gender on human

innate immunity. Surgery 2005;138:275–282.9. Siedlinski M, Klanderman B, Sandhaus RA et al. Association of cigarette

smoking and CRP levels with DNA methylation in a-1 antitrypsin defi-

ciency. Epigenetics 2012;7:720–728.10. Vitale G, Brugts MP, Ogliari G et al. Low circulating IGF-1 bioactivity is

associated with human longevity: Findings in centenarians’ offspring.

Aging (Albany NY) 2012;4:580–589.

ASSESSMENT OF THE HEALTH STATUS OFCENTENARIANS IN THE SOUTH OF CHINA: ACROSS-SECTIONAL STUDY

To the Editor: Centenarians surpass the current human lifeexpectancy by 20 to 25 years, indicating that they mayhave a unique capability to postpone disease and disabilityinto their later years of life. Several studies have revealedthat centenarians escape or delay major age-related dis-eases1–3 and thus could serve as a model for healthy aging.China is the most populous country in the world, and itspopulation aging results in a greater burden of disease.Fortunately, the unique survival advantage of centenariansallows identification of beneficial factors that may helpelderly adults reach a good state of health.

The current study evaluated the health status of 535centenarians from Hainan province, China, in 2010 withthe aim of identifying suitable strategies to improve thehealth of elderly adults. The centenarians were invited toparticipate in a physical examination as shown in Table 1.Blood samples were obtained in the early morning. Height,weight, blood pressure, and clinical biochemical parame-ters were measured following standard laboratory proce-dures. Body mass index (BMI) was calculated to measureoverall adiposity. The diagnosis of type 2 diabetes mellitus(T2DM), hypertriglyceridemia (HTG), and hypertension(HP) was based on reported criteria.4–6 To understand themetabolic status of centenarians, their blood glucose, tri-glyceride, and total cholesterol levels were compared withthose of a retiree population from the same province.7 Theprevalence of T2DM, HTG, and HP was compared withthat of the Third Chronic Noncommunicable Disease andRisk Factor Survey in China.8 The ethics committee atKunming Institute of Zoology, Chinese Academy of Sci-ences approved the study protocol. Written informed con-sent was obtained from all participants. Data were

analyzed using SPSS 13.0 (Beijing Stats Data Mining Co.Ltd., Beijing, China).

The average age of the centenarians (85.0% female,15.0% male) was 102. Average height was 146.7� 0.5 cm, average weight was 36.0 � 0.4 kg, andaverage BMI was 16.7 � 0.1 kg/m2. Only two of 271centenarians for whom information was available wereoverweight, and none were obese. Alanine aminotrans-

Table 1. Physical Examination of Centenarians inHainan Province in 2010

Item n (%)

Skin (n = 510)Normal 236 (46.3)Abnormal pigmentation 237 (46.5)Pale 30 (5.9)Flushed 7 (1.4)

Lymphoid node (n = 435)Touched 432 (99.3)Untouched 3 (0.7)

Spine (n = 426)Normal 239 (56.1)Mild kyphosis 143 (33.6)Severe kyphosis 39 (9.2)Scoliosis 5 (1.2)

Extremities (449)Normal 360 (80.2)Deformity without pain 16 (3.6)Deformity with pain or limitation of motion 72 (16.0)Tetraplegia 1 (0.2)

Heart (n = 409)Normal 314 (76.8)Arrhythmia 35 (8.6)Normal rhythm with cardiac souffle 46 (11.2)Arrhythmia with cardiac souffle 14 (4.9)

Lung (n = 410)Normal 358 (87.3)Moist rales 48 (11.7)Dry rales 4 (1.0)

Abdomen or digestive system (n = 416)Normal 409 (98.3)Abdominal mass 4 (1.0)Gastropathy or gastritis 2 (0.5)Gallstone 1 (0.2)

Cognitive ability (n = 398)Good 361 (90.7)Retardation 27 (6.8)Bad 10 (2.5)

Vision (n = 457)Good 129 (28.2)Decreased 206 (45.1)Weak 71 (15.5)Monocular deprivation 16 (3.5)Blind 35 (7.7)

Hearing (n = 422)Good 158 (37.4)Decreased 183 (43.4)Weak 70 (16.6)Deaf 11 (2.6)

Teeth (n = 400)Complete (28–32) 42 (10.5)Mild loss (20–27) 10 (2.5)Medium loss (10–19) 52 (13.0)Severe loss (1–9) 83 (20.7)No teeth (0) 213 (53.2)

1402 LETTERS TO THE EDITOR JULY 2014–VOL. 62, NO. 7 JAGS

ferase, total protein, albumin, globin, blood urine nitro-gen, creatinine, and uric acid levels were all in normalphysiological ranges. Levels of the important risk factorsfor cardiovascular diseases, blood glucose (101.0 � 1.6mg/dL), triglyceride (114.2 � 3.5 mg/dL), and total cho-lesterol (180.6 � 2.3 mg/dL) were significantly lower thanthose of the general older population (116.1 � 0.9 mg/dL,151.4 � 2.7 mg/dL, and 222.3 � 1.2 mg/dL, respectively)from the same province.7 These results were in goodagreement with results of a previous study.9 Moreover,the prevalence of T2DM (16.9%), HTG (6.5%), and HP(52.9%) was lower in the centenarians than Chinesenational levels (25.0%, 12.9%, and 66.9%, respectively).In addition, only four of 349 centenarians for whominformation was available had benign tumors (hemangi-oma or melanoma). It seems that the incidence of age-related diseases is delayed or reduced in centenarians. Thisrelatively healthy status of centenarians suggests that theycan serve as a good model for a healthy aging study.Additional evidence comes from the observation that morethan 90% of the centenarians were cognitively normal(Table 1).

Nonetheless, some health problems were also observedin the centenarians, although none of these were lifethreatening; 42.8% had kyphosis, 19.6% were deformedin their extremities, 16.0% of them lived with pain ormotion limitation, 4.9% (n = 14) had arrhythmia withcardiac souffle, 11.7% (n = 48) had pulmonary moistrales, 71.8% had weak vision, 62.6% had hearing difficul-ties, and 89.5% had problems chewing (Table 1).

This study has several limitations that deserve atten-tion. One was the difficulty recruiting the centenarians,who were widely distributed geographically, which prohib-ited a definite diagnosis for all diseases. Another is thatsome measurements were based on self-report or subjec-tive judgments of the examiners, increasing the likelihoodof information and recall bias. The third is that informa-tion was missing for some environmental or sociodemo-graphic factors that had been collected in a previousstudy.10

In summary, the survey results reveal that centenarianshave a lower incidence of age-related diseases that have ahigh prevalence and high mortality, despite having somenon-life-threatening illnesses, indicating that they are agood model for a healthy aging study.

Yong-Han He, MDState Key Laboratory of Genetic Resources and Evolution,

Kunming Institute of Zoology, Chinese Academy ofSciences, Kunming, China

KIZ/CUHK Joint Laboratory of Bioresources andMolecular Research in Common Diseases, Kunming,

China

Yun-Xia Zhang, DAgrDepartment of Biochemistry and Molecular Biology,

Hainan Medical College, Haikou, China

Li-Qin Yang, MAgrState Key Laboratory of Genetic Resources and Evolution,

Kunming Institute of Zoology, Chinese Academy ofSciences, Kunming, China

KIZ/CUHK Joint Laboratory of Bioresources andMolecular Research in Common Diseases, Kunming,

China

Xiao-Ping Liao, MBDepartment of Neurology, Affiliated Hospital of Hainan

Medical College, Haikou, China

Qing-Ying Zhang, MDState Key Laboratory of Genetic Resources and Evolution,

Kunming Institute of Zoology, Chinese Academy ofSciences, Kunming, China

Wang-Wei Cai, MDDepartment of Biochemistry and Molecular Biology,

Hainan Medical College, Haikou, China

Qing-Peng Kong, PhDState Key Laboratory of Genetic Resources and Evolution,

Kunming Institute of Zoology, Chinese Academy ofSciences, Kunming, China

KIZ/CUHK Joint Laboratory of Bioresources andMolecular Research in Common Diseases, Kunming,

China

ACKNOWLEDGMENTS

The study was supported by grants from the National BasicResearch Program of China (2013CB530802), KunmingInstitute of Zoology, Chinese Academy of Science (GRE-KF10–12), Yunnan Province (2011FA024, 2013FB069),Chinese Academy of Sciences, Natural Science Foundationof China (31100909, 31322029), and Department of Sci-ence and Technology of Hainan Province (013GHXM0025,ZDXM20090805).

Conflict of Interest: The authors declare that they haveno conflict of interest related to this manuscript.

Author Contributions: Kong, Cai: study concept anddesign. He, Zhang, Yang, Liao, Zhang: acquisition of sub-jects and data, analysis and interpretation of data, manu-script preparation.

Sponsor’s Role: None.

REFERENCES

1. Andersen-Ranberg K, Schroll M, Jeune B. Healthy centenarians do not

exist, but autonomous centenarians do: A population-based study of mor-

bidity among Danish centenarians. J Am Geriatr Soc 2001;49:900–908.2. Engberg H, Oksuzyan A, Jeune B et al. Centenarians—a useful model for

healthy aging? A 29-year follow-up of hospitalizations among 40,000

Danes born in 1905. Aging Cell 2009;8:270–276.3. Hitt R, Young-Xu Y, Silver M et al. Centenarians: The older you get, the

healthier you have been. Lancet 1999;354:652.

4. American Diabetes Association. Diagnosis and classification of diabetes

mellitus. Diabetes Care 2013;36(Suppl 1):S67–S74.5. CADP Committee. China Adult Dyslipidemia Prevention Guide (2007).

Beijing, China: People’s Health Publishing House, 2007.

6. Gu D, Reynolds K, Wu X et al. Prevalence, awareness, treatment, and

control of hypertension in china. Hypertension 2002;40:920–927.7. Zhan YJ. Correlation of cataract prevalence with hypertension, hyperlip-

idemia and hyperglycemia in a community of Haikou. Chinese Gen Pract

2010;13:2714–2716.8. Wang ZH, Wang LH, Li YC et al. Current status of diabetes, hyperten-

sion and dyslipidemia among older Chinese adults in 2010. Zhonghua Yu

Fang Yi Xue Za Zhi 2012;46:922–926.

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9. Gong YY, Xie L, Zhou WP et al. Glucose and lipid profile of a long-lived

rural Han Chinese population and their families in southwest China.

J Am Geriatr Soc 2009;57:567–568.10. Ye JJ, Li JC, Peng L et al. Nonagenarians and centenarians in a rural Han

Chinese population: Lifestyle and epidemics. J Am Geriatr Soc 2009;

57:1723–1724.

CASE REPORTS

ENDOCRINE AND METABOLIC ABNORMALITIESIN A GIRL WITH CHILDHOOD WERNERSYNDROME: CASE REPORT

To the Editor: Werner syndrome (WS) is a rare progeroidsyndrome of autosomal-recessive inheritance that Germanophthalmologist Otto Werner first reported in 1904. Thefrequency of WS is as high as 1 in 40,000 in Japan, withconsanguineous marriage noted in approximately 40% ofcases, although no regional localization of cases has beenrecognized.1,2 Most progeroid phenotypes are clinicallytypical, including the graying and loss of hair; hoarsenessand scleroderma-like skin changes emerging in the 20s;and juvenile cataracts, insulin-resistant diabetes mellitus,hypogonadism, ulceration of the skin, osteoporosis, andsoft tissue calcification arising in the 30s. The most severeand lethal conditions are malignant tumors and cardiovas-cular or cerebrovascular diseases resulting from prematureatherosclerosis in the 40s and 50s.1–4 Mean age at diagno-sis was 36.7 in individuals who presented with typicalsigns of WS.3 In contrast, individuals who develop the dis-ease in childhood are not usually reported primarilybecause of the variety of nonspecific symptoms and lack ofcardinal signs during the teenage years. The case of a girldiagnosed with WS at 17 is herein reported.

The girl’s parents were second cousins without a fam-ily history suggesting the presence of genetic diseases,including progeroid syndromes. The girl was healthy atbirth and exhibited normal growth and development ininfancy. Starting at 6 years old, she gradually developedfacial erythema (Figure 1) and failure to grow. At 10 yearsold, her parents consulted a pediatrician regarding hergrowth failure and chronic fatigue of unknown etiology.Clinical and laboratory examinations identified a diagnosisof hypothyroidism, and levothyroxine treatment wasstarted, but she discontinued the medication after severalmonths. At 17 years old, she again consulted a physicianand was referred to the hospital for systematic evaluation.

She was 141 cm (3.3 standard deviations below themean) tall and weighed 33.2 kg (2.7 standard deviationsbelow the mean), and her body mass index was 16.7 kg/m2.She had slightly gray hair, erythema on both cheeks, anddry skin over her entire body. Laboratory findings demon-strated hepatic dysfunction (aspartate aminotransferase,132 U/L (normal range (NR) 13–33 U/L); alanine amino-transferase, 252 U/L (NR 6–30 U/L); gamma-glutamyltranspeptidase, 51 U/L (NR 10–47 U/L)) and dyslipidemia(triglycerides, 221 mg/dL (NR, 30–149 mg/dL); low-den-sity lipoprotein cholesterol, 140 mg/dL (NR <139)), withnormal serum creatine phosphokinase, blood urea nitro-gen, and creatinine levels. Metabolic and endocrinologicalstudies revealed hypothyroidism (basal thyroid-stimulating

hormone (TSH), 11.22 lU/mL (NR 0.27–4.20 lU/mL);free thyroxine, 0.82 ng/dL (NR 1.00–1.80 ng/dL)) with aremarkably high TSH level after a thyrotropin releasinghormone loading test (58.48 lU/mL at 60 minutes (NR10–25 lU/mL)). An oral glucose tolerance test with 75-goral glucose loading showed borderline glucose intolerancewith remarkable insulin resistance (blood glucose, 197 mg/dL (NR 60–125 mg/dL); insulin, 563 lU/mL at 120 min-utes (NR <300)). Ultrasonography demonstrated an atro-phic thyroid and marked fatty liver. Brachial–ankle pulsewave velocity indicated slight arteriosclerotic changes(right 1,188 cm/s, left 1,157 cm/s, mean 952 � 103 cm/s).Bilateral ovary hypoplasia and a right ovarian cyst weredetected on magnetic resonance imaging. Ophthalmologi-cal study revealed bilateral cataracts. There were no signsof osteoporosis of the lumbar spine (bone mineral density0.968 g/cm3; Z-score �0.4). No calcification of the Achil-les tendon, a cardinal sign of WS in adulthood,1 wasdetected on X-ray examination. Genetic tests identified ahomozygous mutation of IVS25–1G>C in the WRN gene,one of the most common mutations in Japanese individualswith WS. Medical treatment with levothyroxine sodiumhydrate at a dose of 100 lg/d quickly normalized the girl’sthyroid function, with an associated increase in her vigor.Subsequent biguanide therapy (750 mg/d) was discontin-ued within 1 week because of abdominal pain.

Based on the clinical features reported in previousstudies, the characteristic abnormalities in metabolismobserved in individuals with WS are mainly attributed toperipheral lipoatrophy with insulin insensitivity or dyslipi-demia.5 Endocrinological problems in the setting of WSprimarily derive from the impaired secretion of hormonesdue to premature aging of endocrine organs, and empiri-cally, hypogonadism, hypothyroidism, and hypopituitarismare the major endocrinological concerns in individualswith WS. Although these conditions may be present inchildhood, no clinical studies have reported such features,probably because of the difficulty in diagnosing WS inindividuals with nonspecific symptoms. The present casetherefore provides important and valuable information.First, hypothyroidism of atrophic thyroid glands in addi-tion to pituitary and hypothalamic dysfunction can appearas early as 10 years of age. Second, marked insulininsensitivity due to a lipodystrophic phenotype can arise in

Figure 1. Facial erythema and beak-like appearance.

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