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March 2008 Ekronicle

Topics

Aging
Oxidative Stress
Nutrition
Hormones
Cardiovascular
Diabetes
Glossary

Aging

Oxidative Stress Leads to Tissue Deterioration and Aging

The Role of Mitochondrial DNA Mutations in Aging and Sarcopenia: Implications for the Mitochondrial Vicious Cycle Theory of Aging

Abbreviated Abstract: Aging is associated with a progressive loss of skeletal muscle mass and strength and the mechanisms mediating these effects likely involve mitochondrial DNA (mtDNA) mutations, mitochondrial dysfunction and the activation of mitochondrial-mediated apoptosis. Here, we examine the evidence supporting a causative role for mtDNA mutations in aging and sarcopenia. Moreover, we critically discuss and dispute an important part of the mitochondrial 'vicious cycle' theory of aging which proposes that accumulation of mtDNA mutations may lead to an enhanced mitochondrial ROS production and ever increasing oxidative stress which ultimately leads to tissue deterioration and aging.

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Hiona A, Leeuwenburgh C. Exp Gerontol. 2008 Jan;43(1):24-33. Epub 2007 Oct 4.

Women Who Are Healthy and of Normal Weight Have a Life Expectancy of Another 22.1 Years

Weight, Mortality, Years of Healthy Life, and Active Life Expectancy in Older Adults

Abbreviated Abstract: To determine whether weight categories predict subsequent mortality and morbidity in older adults. DESIGN: Multistate life tables, using data from the Cardiovascular Health Study, a longitudinal population-based cohort of older adults. PARTICIPANTS: Five thousand eight hundred eighty-eight adults aged 65 and older at baseline. RESULTS: Women who are healthy and of normal weight at age 65 have a life expectancy of 22.1 years. Of that, they spend, on average, 9.6 years as overweight or obese and 5.3 years in fair or poor health. For both men and women, being underweight at age 65 was associated with worse outcomes than being normal weight, whereas being overweight or obese was rarely associated with worse outcomes than being normal weight and was sometimes associated with significantly better outcomes.

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Diehr P, O'Meara ES, Fitzpatrick A, Newman AB, Kuller L, Burke G. J Am Geriatr Soc. 2008 Jan;56(1):76-83. Epub 2007 Nov 20.

Oxidative Stress

Long-Term Physical Activity In Older Adults Preserves Antioxidant Capacity

Physical Activity Modulates Heat Shock Protein-72 Expression and Limits Oxidative Damage Accumulation in a Healthy Elderly Population Aged 60-90 Years

Abbreviated Abstract: Reactive oxygen species production increases during aging, whereas protective mechanisms such as heat shock proteins (HSPs) or antioxidant capacity are depressed. Physical activity has been hypothesized to provide protection against oxidative damage during aging, but results remain controversial. This study aimed to investigate the effect of different levels of physical activity during aging on Hsp72 expression and systemic oxidative stress at rest and in response to maximal exercise. CONCLUSIONS: The key finding of this study is that, in people aged 60 to 90 years, long-term high level of physical activity preserved antioxidant capacity and limited oxidative damage accumulation. It also downregulated Hsp72 expression, an adaptation potentially resulting from lower levels of oxidative damage.

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Simar D, Malatesta D, Badiou S, Dupuy AM, Caillaud C. J Gerontol A Biol Sci Med Sci. 2007 Dec;62(12):1413-9.

Exercise Training Improves Glycemic Control and Oxidative Stress

Effect of Aerobic Exercise on Oxidative Stress in Patients With Type 2 Diabetes Mellitus

Abbreviated Abstract: The purpose of this study was to determine whether moderate-intensity exercise training reduces oxidative stress in patients with type 2 diabetes mellitus over 12 months. The patients were divided into 3 groups: aerobic training combined with the use of a fitness center (group A, n = 43), aerobic training only (group B, n = 44), or controls (group C, n = 16). There was a significant positive linear association between percentage changes in urinary 8-OHdG and glycated albumin levels over the 12 months. In conclusion, aerobic exercise training improved glycemic control and reduced oxidative stress in patients with type 2 diabetes mellitus. Furthermore, improvement in glycemic control was associated with a reduction in oxidative stress.

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Nojima H, Watanabe H, Yamane K, Kitahara Y, Sekikawa K, Yamamoto H, Yokoyama A, Inamizu T, Asahara T, Kohno N; the Hiroshima University Health Promotion Study Group. Metabolism. 2008 Feb;57(2):170-176.

Fat Increases in Trunk and Arms of Postmenopausal Women

Oxidative Stress, Body Fat Composition, and Endocrine Status in pre- and postmenopausal women

Abbreviated Abstract: To evaluate the role of menopause on the regional composition and distribution of fat in women and eventual correlations with the oxidative state. DESIGN: In this observational clinical investigation, 90 women (classified for menopause status according to Stages of Reproductive Aging Workshop criteria) were evaluated for body mass composition and fat distribution by dual-energy x-ray absorptiometry and for oxidative status by determination of serum hydroperoxide levels and residual antioxidant activity. CONCLUSIONS: The results of our investigation demonstrate that fat content increases in the upper part of the body (trunk and arms) in postmenopause and that age is the main determinant of this increase. During the comparison of premenopausal and postmenopausal women, we also detected a significant increase in antioxidant status. Apparently this change is mainly related to menopausal endocrine and fat changes. Link to Full Abstract. Must be a member to access full article. Click here to sign in.

Pansini F, Cervellati C, Guariento A, Stacchini MA, Castaldini C, Bernardi A, Pascale G, Bonaccorsi G, Patella A, Bagni B, Mollica G, Bergamini CM. Menopause. 2008 Jan-Feb;15(1):112-8.

Nutrition

Fatty Fish Influences Muscle Function in Older Men and Women

Diet and Its Relationship with Grip Strength in Community-Dwelling Older Men and Women: The Hertfordshire Cohort Study

Abbreviated Abstract: To examine relationships between diet and grip strength in older men and women and to determine whether prenatal growth modifies these relationships. PARTICIPANTS: Two thousand nine hundred eighty-three men and women aged 59 to 73 who were born and still living in Hertfordshire, United Kingdom. MEASUREMENTS: Weight at birth recorded in Health Visitor ledgers; current food and nutrient intake assessed using an administered food frequency questionnaire; and grip strength measured using a handheld dynamometer. CONCLUSION: These data suggest that fatty fish consumption can have an important influence on muscle function in older men and women. This raises the possibility that the antiinflammatory actions of omega-3 fatty acids may play a role in the prevention of sarcopenia.

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Robinson SM, Jameson KA, Batelaan SF, Martin HJ, Syddall HE, Dennison EM, Cooper C, Sayer AA. J Am Geriatr Soc. 2008 Jan;56(1):84-90. Epub 2007 Nov 15.

More Studies Need to Assess the Effect of Obesity on Physical Activity

Fat Mass But Not Fat-Free Mass is Related to Physical Capacity in Well-Functioning Older Individuals: Nutrition as a Determinant of Successful Aging (NuAge) - The Quebec Longitudinal Study

Abbreviated Abstract: Aging is associated with increases in fat mass (FM) and decreases in fat-free mass (FFM) that may affect physical capacity. However, it is not clear whether high FM or low FFM contribute more to a reduction in physical capacity. METHODS: A structural equation modeling strategy was used to test an explanatory model of the association between body composition and physical capacity. The concept of physical capacity was assessed by walking speed at a normal pace and the one leg stand test. To test the model, 904 men and women between 67 and 84 years old were studied. Body composition was measured by dual-energy x-ray absorptiometry (DXA). Confounding factors related to body composition and physical capacities were included in the explanatory model (physical activity level, age, gender, and number of reported diseases). CONCLUSION: FM was significantly and inversely correlated with physical capacity, whereas FFM was not associated when controlled for other potential confounding variables. More studies are needed to investigate the effect of different levels of obesity on physical capacity in older individuals.

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Bouchard DR, Beliaeff S, Dionne IJ, Brochu M. J Gerontol A Biol Sci Med Sci. 2007 Dec;62(12):1382-8.

Hormones

Low Vitamin D Levels Are Common in the Elderly

Hypovitaminosis D and Parathyroid Hormone Response In the Elderly: Effects on Bone Turnover and Mortality

Abbreviated Abstract: To investigate whether absence of secondary hyperparathyroidism in the presence of hypovitaminosis D has altered bone turnover, fracture risk and mortality. DESIGN: A prospective cohort study. PATIENTS: A total of 1280 older men and women living in residential care facilities. MEASUREMENTS: We measured baseline serum 25-hydroxyvitamin D (25OHD), serum intact PTH, serum amino-terminal propeptide of type I collagen (PINP) and serum carboxy-terminal telopeptide of type I collagen (CTX-I). Deaths and fractures were recorded prospectively. CONCLUSION: Absence of secondary hyperparathyroidism in the presence of hypovitaminosis D appears to be common in the frail elderly and is associated with longer survival, similar to that observed in vitamin D-replete elderly subjects.

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Chen JS, Sambrook PN, March L, Cameron ID, Cumming RG, Simpson JM, Seibel MJ. Clin Endocrinol (Oxf). 2008 Feb;68(2):290-8. Epub 2007 Sep 14.

Growth Hormone Improved Maximal Oxygen in Growth Hormone Deficient Adults

Growth Hormone Replacement Therapy in Adults with Growth Hormone Deficiency Improves Maximal Oxygen Consumption Independently of Dosing Regimen or Physical Activity

Abbreviated Abstract: Several studies have demonstrated an improvement in aerobic exercise capacity with 6 months of GH replacement in adults with GH deficiency (GHD). OBJECTIVE: The objective of the study was to determine whether improvements in aerobic exercise capacity with GH treatment in adults with GHD are related to changes in physical activity or affected by the GH dosing regimen. DESIGN: This was a randomized, two-arm, parallel, open-label study. RESULTS: In the group as a whole, VO2 max increased significantly (by 9%) from baseline (19.1+/- 0.89 ml/kg.min) to end point (21.6 +/- 1.23 ml/kg.min, P = 0.010). Compared with baseline, VO2 max also changed significantly within the individualized dose titration regimen group (+2.5 +/- 0.98 ml/kg.min, P =0.034) but not within the fixed body weight-based dosing regimen group (+1.2 +/- 0.78 ml/kg.min, P = 0.15), although these changes from baseline were not significantly different between the two groups. VO2 at lactate threshold, VO2 at ventilatory threshold, and weekly energy expenditure also did not change. CONCLUSIONS: GH replacement therapy in GH-deficient adults improved VO2 max similarly with both dosing regimens, without any influence of physical activity. There was no effect on submaximal exercise performance.

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Hartman ML, Weltman A, Zagar A, Qualy RL, Hoffman AR, Merriam GR. J Clin Endocrinol Metab. 2008 Jan;93(1):125-30. Epub 2007 Oct 23.

Testosterone Increases Total Fat Free Mass and Total Body and Thigh Muscle

Testosterone Therapy Prevents Gain in Visceral Adipose Tissue and Loss of Skeletal Muscle in Nonobese Aging Men

Abbreviated Abstract: Trials of testosterone therapy in aging men have demonstrated increases in fat-free mass (FFM) and skeletal muscle and decreases in fat mass (FM) but have not reported the impact of baseline body composition. OBJECTIVE: The objective of the study was to determine the effect, in nonobese aging men with symptoms of androgen deficiency and low-normal serum testosterone levels, of testosterone therapy on total and regional body composition and hormonal and metabolic indices. CONCLUSION: Testosterone therapy, relative to placebo, selectively lessened visceral fat accumulation without change in total body FM and increased total body FFM and total body and thigh skeletal muscle mass. Further studies are needed to determine the impact of these body compositional changes on markers of metabolic and cardiovascular risk.

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Allan CA, Strauss BJ, Burger HG, Forbes EA, McLachlan RI. J Clin Endocrinol Metab. 2008 Jan;93(1):139-46. Epub 2007 Oct 16.

Transdermal Patch Believe to Relieve Symptoms of Vulvovaginal Atrophy

The Effect of Transdermal and Vaginal Estrogen Therapy on Markers of Postmenopausal Estrogen Status

Abbreviated Abstract: To compare serum 17beta-estradiol (E2), estrone (E1), estrone sulfate, follicle-stimulating hormone, luteinizing hormone, sex hormone-binding globulin, vaginal pH, and the vaginal maturation indices in women using a low-dose transdermal patch releasing 14 microg of E2 per day and a vaginal ring releasing 7.5 microg of E2 per day. DESIGN: Twenty-four postmenopausal women were randomly assigned to either the patch (n = 12) or the ring (n = 12) for a 12-week study period. Serum E2, E1, estrone sulfate, follicle-stimulating hormone, luteinizing hormone, and sex hormone-binding globulin were measured by immunoassay at baseline and 6 and 12 weeks. Vaginal pH was determined at baseline and 6 and 12 weeks. Vaginal cytologic examinations for vaginal maturation index were done at baseline and 12 weeks. CONCLUSIONS: A transdermal E2 skin patch releasing 14 microg of E2 per day had an effect on vaginal pH and vaginal maturation indices similar to that of a vaginal E2 ring releasing 7.5 microg of E2 per day. Therefore, this patch is likely to relieve symptoms of vulvovaginal atrophy.

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Gupta P, Ozel B, Stanczyk FZ, Felix JC, Mishell DR Jr. Menopause. 2008 Jan-Feb;15(1):94-7.

OB/GYN Should Work to Identify At-Risk Perimenopausal Women

Management of Cardiovascular Risk in the Perimenopausal Women: A Consensus Statement of European Cardiologists and Gynecologists

Abbreviated Abstract: Cardiovascular risk is poorly managed in women, especially during the menopausal transition when susceptibility to cardiovascular events increases. Clear gender differences exist in the epidemiology, symptoms, diagnosis, progression, prognosis and management of cardiovascular risk. Key risk factors that need to be controlled in the perimenopausal woman are hypertension, dyslipidemia, obesity and other components of the metabolic syndrome, with the avoidance and careful control of diabetes. Hypertension is a particularly powerful risk factor and lowering of blood pressure is pivotal. Hormone replacement therapy is acknowledged as the gold standard for the alleviation of the distressing vasomotor symptoms of the menopause, but the findings of the Women's Health Initiative (WHI) study generated concern for the detrimental effect on cardiovascular events. Thus, hormone replacement therapy cannot be recommended for the prevention of cardiovascular disease. Whether the findings of WHI in older postmenopausal women can be applied to younger perimenopausal women is unknown. It is increasingly recognized that hormone therapy is inappropriate for older postmenopausal women no longer displaying menopausal symptoms. Both gynecologists and cardiovascular physicians have an important role to play in identifying perimenopausal women at risk of cardiovascular morbidity and mortality, and should work as a team to identify and manage risk factors, such as hypertension.

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Collins P, Rosano G, Casey C, Daly C, Gambacciani M, Hadji P, Kaaja R, Mikkola T, Palacios S, Preston R, Simon T, Stevenson J, Stramba-Badiale M. Climacteric. 2007 Dec;10(6):508-26

Cardiovascular

The Role of Inflammation in Coronary Artery Calcification

The Role of Inflammation in Coronary Artery Calcification

Abbreviated Abstract: Vascular calcification is an age-dependent, common finding in human coronary arteries and begins as early as the second decade of life, just after fatty streak formation. Current diagnostic methods for coronary artery calcification (CAC) are usually traditional coronary angiography, intravascular ultrasound (IVUS), electron beam computed tomography (EBCT) and multi-slice computed tomography (MSCT) while treatment for patients with calcified coronary arteries is troublesome. Several lines of evidence suggest that inflammation plays a major role in the development of atherosclerosis as well as its clinical manifestations. Recent study showed that inflammatory process might be also involved in coronary calcification. Accordingly, measurements of inflammatory markers such as C-reactive protein (CRP) may in part reflect indices of atherosclerosis, such as coronary calcification, and are likely to provide distinct information regarding cardiovascular risk. In this article, we review the current evidence of relationship between coronary calcification and inflammation for purpose of drawing the more attention on the inflammatory mechanism of coronary calcification, which may change our research as well as therapeutic strategies for coronary calcification in the future.

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Li JJ, Zhu CG, Yu B, Liu YX, Yu MY. The Role of Inflammation in Coronary Artery Calcification. Ageing Res Rev. 2007 Dec;6(4):263-70.

Physicians Have Been Sensitized To the Potential of a Missed Diagnosis of Acute Coronary Syndrome

The Challenge of Women and Heart Disease

Abbreviated Abstract: Do women and men experience different symptoms with acute coronary syndrome (ACS)? If differences exist, are they sufficient to warrant a different public health message? Should clinicians factor in sex when trying to diagnose ACS in the emergency department? Do other patient characteristics (such as age, race, or the presence of diabetes) significantly affect clinical presentation? These questions are important in an era when the American public has become increasingly aware that ACS is not a male disease and women proudly wear a pin shaped as a red dress to demonstrate their vulnerability to heart disease.1 Physicians have been sensitized to the potential of a missed diagnosis of ACS, often through personal experience with 1 or more female patients who delayed seeking treatment for hours or even days, thereby postponing life-saving treatment.

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Dracup K. The Challenge of Women and Heart Disease. Arch Intern Med. 2007;167(22):2396.

Advanced Coronary Artery Calcium Identified a Set of Lower-Risk Women as High Risk for Cardiovascular Diseases

Coronary Artery Calcium Scores and Risk for Cardiovascular Events in Women Classified as "Low Risk" Based on Framingham Risk Score: The Multi-Ethnic Study of Atherosclerosis (MESA)

Abbreviated Abstract: To assess coronary artery calcium (CAC) score and subsequent risk for coronary heart disease (CHD) and cardiovascular (CVD) events among asymptomatic women judged to be at low risk by the Framingham risk score (FRS), a common approach for determining 10-year absolute risk for CHD. Based on population survey data, 95% of American women are considered at low risk based on FRS. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) included 3601 women aged 45 to 84 years at baseline. The CAC score was measured by coronary computed tomography. Cox proportional hazard models were used to examine the CHD and CVD risk associated with CAC score among women classified as "low risk" based on FRS. CONCLUSIONS: The presence of CAC in women considered to be at low risk based on FRS was predictive of future CHD and CVD events. Advanced CAC identified a subset of low-risk women at higher risk based on current risk stratification strategies.

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Lakoski SG, Greenland P, Wong ND, Schreiner PJ, Herrington DM, Kronmal RA, Liu K, Blumenthal RS. Arch Intern Med. 2007 Dec 10;167(22):2437-42.

Diabetes

Insulin Resistance of Protein Metabolism Differs in Men and Women

Insulin Resistance of Protein Metabolism in Type 2 Diabetes

Abbreviated Abstract: We previously demonstrated that 1) obesity impairs and 2) sex influences insulin sensitivity of protein metabolism, while 3) poor glycemic control in type 2 diabetes accelerates protein turnover in daily fed-fasted states. We hypothesized that type 2 diabetes alters the insulin sensitivity of protein metabolism and that sex modulates it. RESEARCH DESIGN AND METHODS: Hyperinsulinemic (approximately 570 pmol/l), euglycemic (5.5 mmol/l), and isoaminoacidemic (kept at postabsorptive concentrations) clamps were performed in 17 hyperglycemic type 2 diabetic subjects and 23 subjects without diabetes matched for age and body composition, after 7 days on a inpatient, protein-controlled, isoenergetic diet. Glucose and leucine kinetics were determined using tracers. CONCLUSIONS: During our clamp, men with type 2 diabetes have greater insulin resistance of protein metabolism than that conferred by excess adiposity itself, whereas women do not. These results may have implications for dietary protein requirements.

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Pereira S, Marliss EB, Morais JA, Chevalier S, Gougeon R. Diabetes. 2008 Jan;57(1):56-63. Epub 2007 Oct 16.

GLOSSARY

Mitochondrial: Any of various round or long cellular organelles of most eukaryotes that are found outside the nucleus, produce energy for the cell through cellular respiration, and are rich in fats, proteins, and enzymes -- called also chondriosome

Oxidative Stress: Physiological stress on the body that is caused by the cumulative damage done by free radicals inadequately neutralized by antioxidants and that is held to be associated with aging

Hypovitaminosis: Disease (as pellagra) resulting from a deficiency of one or more vitamins.

Parathyroid Hormone: A hormone of the parathyroid gland that regulates the metabolism of calcium and phosphorus in the body. (Parathyroid Gland: Any of usually four small endocrine glands that are adjacent to or embedded in the thyroid gland, are composed of irregularly arranged secretory epithelial cells lying in a stroma rich in capillaries, and produce parathyroid hormone.)

Hyperparathyroidism: The presence of excess parathyroid hormone in the body resulting in disturbance of calcium metabolism with increase in serum calcium and decrease in inorganic phosphorus, loss of calcium from bone, and renal damage with frequent kidney-stone formation.

Visceral Fat: Of, relating to, or located on or among the viscera. (Viscera: an internal organ of the body; especially one, such as the heart, liver, or intestine, located in the large cavity of the trunk.)