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Life Extension Magazine

Life Extension Magazine December 2012
Abstracts  

7-KETO

Age-related differences in fat-free mass, skeletal muscle, body cell mass and fat mass between 18 and 94 years.

OBJECTIVE: To determine (1) lean and fat body compartments, reflected by fat-free mass (FFM), appendicular skeletal muscle mass (ASMM), body cell mass (BCM), total body potassium (TBK), fat mass and percentage fat mass, and their differences between age groups in healthy, physically active subjects from 18 to 94 y of age; and (2) if the rate of decrease in any one of the parameters by age might be accelerated compared to others. METHODS: A total of 433 healthy ambulatory Caucasians (253 men and 180 women) aged 18--94 y were measured by dual-energy X-ray absorptiometry (DXA) and whole body scintillation counter (TBK counter) using a large sodium iodide crystal (203 mm diameter). RESULTS: The ASMM change (-16.4 and -12.3% in men and women, respectively) in >75 y-old compared to 18 to 34-y-old subjects was greater than the FFM change (-11.8 and -9.7% in men and women, respectively) and this suggests that skeletal muscle mass decrease in older subjects was proportionally greater than non-skeletal muscle mass. BCM (-25.1 and -23.2% in men and women, respectively) and TBK differences were greater than the differences in FFM or ASMM suggesting altered composition of FFM in older subjects. Women had lower peak FFM, ASMM, BCM and TBK than men. CONCLUSIONS: The decline in FFM, ASMM, BCM and TBK is accelerated in men and women after 60 y of age and FFM, ASMM, BCM and TBK are significantly lower than in younger subjects. Fat mass continued to increase until around 75 y.

Eur J Clin Nutr. 2001 Aug;55(8):663-72

Differences between young and old females in the five levels of body composition and their relevance to the two-compartment chemical model.

BACKGROUND: Body composition differs between young and old females, although the magnitude of these age-related changes remains uncertain. This uncertainty persists because methodology applied in earlier studies required assumptions that may be age-dependent and also because studies included young and old subjects who differed substantially in body size and health status. METHODS: To resolve these earlier concerns we examined components at the atomic, molecular, cellular, tissue-system, and whole body levels of body composition in 19 weight- and height-matched pairs of young (age 19-35 yrs) and old (age > 65 yrs) healthy White females. Isotope dilution, dual photon, whole-body counting, hydrodensitometry, and anthropometric methods were used either alone or in combination to produce multicomponent models. RESULTS: Old females had significantly more fat, greater truncal skinfolds and circumferences, and significantly less fat-free body mass (FFM), total body potassium (TBK), total body water (TBW), and bone mineral than did their young matched counterparts. Skeletal muscle mass was less in the old females, although the magnitude of the difference from young females varied between the three indices examined. The main assumptions (i.e., TBW/FFM = 0.73 kg/kg and density of FFM = 1.100 g/cc) which the widely used two-compartment TBW and hydrodensitometry methods are based on were not significantly different in young and old females. In contrast, the main assumed steady-state value for the two-compartment TBK method (TBK/FFM = 64.2 mmol/kg) was significantly lower (p < .001) in the old females. CONCLUSION: New approaches thus allow for a critical reexamination of body composition in elderly subjects, and these methods also give new insight into less complex widely used body composition techniques.

J Gerontol. 1994 Sep;49(5):M201-8

Total body mass, fat mass, fat-free mass, and skeletal muscle in older people: cross-sectional differences in 60-year-old persons.

OBJECTIVES: To evaluate body composition parameters, including fat-free mass (FFM), appendicular skeletal muscle mass (ASMM), relative skeletal muscle mass (RSM) index, body cell mass (BCM), BCM index, total body potassium (TBK), fat mass, percentage fat mass (FM), and their differences between age groups and to evaluate the frequency of sarcopenia in healthy older subjects. DESIGN: Cross-sectional, nonrandomized study. SETTING: Outpatient clinic. PARTICIPANTS: Ninety-one healthy men and 100 healthy women age 60 and older. MEASUREMENTS: FFM, ASMM, FM, and percentage fat mass by whole-body dual-energy x-ray absorptiometry; TBK, BCM, and TBK/FFM ratio by whole body potassium-40 counter. RESULTS: All lean body mass parameters were significantly (P <.05) lower in subjects age 80 and older than in those age 70 to 79, except ASMM in women. Mean FFM was 4.2 kg (7.3%) lower in men age 80 and older than in those younger than 70 and 2.9 kg (6.8%) lower in women age 80 and older than in those younger than 70. The skeletal muscle mass, reflected by ASMM, decreased more than FFM. This suggests that nonskeletal muscle mass is proportionally preserved during aging. Forty-five percent of men and 30% of women were sarcopenic by definition of BCM index and 11.0% of men and women by definition of RSM index. CONCLUSIONS: Significant age-related differences exist in body composition of older men and women between age 60 and 95. The greater decrease in TBK and BCM than the decrease in FFM and skeletal muscle mass suggests changing composition of FFM with age. Lack of agreement between two independent sarcopenia indexes suggests that further refinement in the definition of a sarcopenia index is necessary.

J Am Geriatr Soc. 2001 Dec;49(12):1633-40

HUM5007, a novel combination of thermogenic compounds, and 3-acetyl-7-oxo-dehydroepiandro-sterone: each increases the r esting metabolic rate of overweight adults.

This study tested the hypothesis that 3-acetyl-7-oxo-dehydroepiandrosterone alone (7-Keto) and in combination with calcium citrate, green tea extract, ascorbic acid, chromium nicotinate and cholecalciferol (HUM5007) will increase the resting metabolic rate (RMR) of overweight subjects maintained on a calorie-restricted diet. In this randomized, double-blind, placebo-controlled, crossover trial, overweight adults on a calorie-restricted diet were randomized to three 7-day treatment periods with 7-Keto, HUM5007 or placebo. Resting metabolic rate was measured by indirect calorimetry at the beginning and end of each treatment period with a 7-day washout between testing periods. Of 45 subjects enrolled, 40 completed the study (30 women, 10 men; mean age, 38.5 years; mean mass index, 32.0 kg/m(2)). During the placebo treatment, RMR decreased by 3.9% (75+/-111 kcal/day; mean+/-S.D.); however, RMR increased significantly by 1.4% (21+/-115 kcal/day) and 3.4% (59+/-118 kcal/day) during the 7-Keto and HUM5007 treatment periods, respectively (each compared to placebo, P=.001). No significant differences were found between the treatment periods with respect to compliance or adverse events. In this study, the administration of HUM5007 or 7-Keto reversed the decrease in RMR normally associated with dieting. HUM5007 and 7-Keto increased RMR above basal levels and may benefit obese individuals with impaired energy expenditure. HUM5007 and 7-Keto were generally well tolerated and no serious adverse events were reported.

J Nutr Biochem. 2007 Sep;18(9):629-34

How short-term transdermal treatment of men with 7-oxo-dehydroepiandrosterone influence thyroid function.

Dehydroepiandrosterone may influence thyroid function. Its metabolite, 7-oxo-dehydroepiandrosterone, a precursor of immunomodulatory 7-hydroxylated metabolites and thermogenic agent, belongs to candidates of steroid replacement therapy. The question was addressed whether its application does influence laboratory parameters of thyroid function. 7-Oxo-dehydroepiandrosterone in the form of emulgel, 25 mg/day, was applied transdermally to 21 healthy men for 8 consecutive days. Morning blood was collected before the treatment (Day 0, Stage 1), during treatment (Day 5, Stage 2), on the first day after the last administration (Day 9, Stage 3), one week (Day 16, Stage 4), and 9 weeks (Day 72, Stage 5) after treatment termination. The levels of thyrotropin, free thyroxine and triiodothyronine, dehydroepiandrosterone, its sulfate and its 7-hydroxyepimers were measured. The changes were evaluated by analysis of variance and correlation analysis. During treatment a significant rise of 7beta-hydroxy-dehydroepiandrosterone was observed, which persisted 1 week after treatment termination. No changes were observed in dehydroepiandrosterone and its sulfate. Though a slight but significant rise of TSH and of both thyroid hormones occurred during treatment, its levels soon returned to the basal values. It was concluded that treatment of 7-oxo-dehydroepiandrosterone affects the thyroid parameters only temporarily and that it provides a considerable persistent amount of 7beta-hydroxy-dehydroepiandrosterone.

Physiol Res. 2006;55(1):49-54

Ergosteroids: induction of thermogenic enzymes in liver of rats treated with steroids derived from dehydroepiandrosterone.

Dehydroepiandrosterone (DHEA), an intermediate in the biosynthesis of testosterone and estrogens, exerts several physiological effects not involving the sex hormones. When fed to rats it induces the thermogenic enzymes mitochondrial sn-glycerol-3-phosphate dehydrogenase and cytosolic malic enzyme in their livers. Animals and humans, and their excised tissues, are known to hydroxylate DHEA at several positions and to interconvert 7 alpha-hydroxy-DHEA, 7 beta-hydroxy-DHEA, 7-oxo-DHEA, and the corresponding derivatives of androst-5-enediol. We report here that these 7-oxygenated derivatives are active inducers of these thermogenic enzymes in rats and that the 7-oxo derivatives are more active than the parent steroids. We postulate that the 7 alpha-hydroxy and 7-oxo derivatives are on a metabolic pathway from DHEA to more active steroid hormones. These 7-oxo steroids have potential as therapeutic agents because of their increased activity and because they are not convertible to either testosterone or estrogens.

Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6617-9

Ergosteroids. II: Biologically active metabolites and synthetic derivatives of dehydroepiandrosterone.

An improved procedure for the synthesis of 3 beta-hydroxyandrost-5-ene-7,17-dione, a natural metabolite of dehydroepiandrosterone (DHEA) is described. The synthesis and magnetic resonance spectra of several other related steroids are presented. Feeding dehydroepiandrosterone to rats induces enhanced formation of several liver enzymes among which are mitochondrial sn-glycerol 3-phosphate dehydrogenase (GPDH) and cytosolic malic enzyme. The induction of these two enzymes, that complete a thermogenic system in rat liver, was used as an assay to search for derivatives of DHEA that might be more active than the parent steroid. Activity is retained in steroids that are reduced to the corresponding 17 beta-hydroxy derivative, or hydroxylated at 7 alpha or 7 beta, and is considerably enhanced when the 17-hydroxy or 17-carbonyl steroid is converted to the 7-oxo derivative. Several derivatives of DHEA did not induce the thermogenic enzymes whereas the corresponding 7-oxo compounds did. Both short and long chain acyl esters of DHEA and of 7-oxo-DHEA are active inducers of the liver enzymes when fed to rats. 7-Oxo-DHEA-3-sulfate is as active as 7-oxo-DHEA or its 3-acetyl ester, whereas DHEA-3-sulfate is much less active than DHEA. Among many steroids tested, those possessing a carbonyl group at position 3, a methyl group at 7, a hydroxyl group at positions 1, 2, 4, 11, or 19, or a saturated B ring, with or without a 4-5 double bond, were inactive.

Steroids. 1998 Mar;63(3):158-65

Clinical relevance of age-related immune dysfunction.

Immunosenescence is the state of dysregulated immune function that contributes to the increased susceptibility to infection of the elderly. Extensive studies of inbred laboratory animals and very healthy elderly humans have identified changes in immunity; these studies have identified limited phenotypic and functional changes in the T cell component of adaptive immunity. However, no compelling scientific evidence has shown that these changes have direct relevance to the common infections seen in the aged population. This perspective will attempt to shed light on this dilemma. First, it will review clinically relevant infections in the elderly, focusing on influenza and influenza virus vaccination and how chronic illness contributes to increased risk and severity of infection and/or failed vaccine response. Second, key changes in immunity will be reviewed, keeping a perspective of the impact of confounding variables in addition to age but focusing on age-related changes in the interaction of the innate and acquired components of immunity. If the goal is to prevent serious infections in the elderly, it appears that the field of geriatric immunology and/or infectious diseases is faced with the tremendous challenge of studying a very diverse population, including mildly immunocompromised/chronically ill individuals and very healthy elderly.

Clin Infect Dis. 2000 Aug;31(2):578-85

Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood.

In a cross-sectional study, serum dehydroepiandrosterone sulfate (DS) concentrations were measured in 981 men and 481 women, aged 11-89, yr. The resulting data were asymetrically distributed and were normalized by logarithmic transformation and analyzed by 5-yr age grouping (e.g. 15-19 yr, 20-24 yr, etc.). The DS concentration peaked at age 20-24 yr in men (logarithmic mean, 3470 ng/ml) and at age 15-19 yr in women (log mean, 2470 ng/ml). Mean values then declined steadily in both sexes (log mean at greater than 70 yr of age, 670 ng/ml in men and 450 ng/ml in women) and were significantly higher in men than women at ages from 20-69 yr. Analysis of 517 randomly selected sera (from women) which had been stored frozen for 10-15 yr gave results indistinguishable from values obtained from fresh specimens. In a supplementary study, a longitudinal analysis of weekly specimens from 4 normal men, aged 36-59 yr, revealed individual variability (mean coefficient of variation, 19%) and failed to demonstrate any monthly, seasonal, or annual rhythmicity. Based on the above analyses, a table of normal serum DS ranges for adult men and women is presented for use as a clinical reference.

J Clin Endocrinol Metab. 1984 Sep;59(3):551-5