Abstract:
Aging is characterized by a progressive loss of muscle mass and muscle strength. Declines in skeletal muscle mitochondria are thought to play a primary role in this process. Mitochondria are the major producers of reactive oxygen species, which damage DNA, proteins, and lipids if not rapidly quenched. Animal and human studies typically show that skeletal muscle mitochondria are altered with aging, including increased mutations in mitochondrial DNA, decreased activity of some mitochondrial enzymes, altered respiration with reduced maximal capacity at least in sedentary individuals, and reduced total mitochondrial content with increased morphological changes. However, there has been much controversy over measurements of mitochondrial energy production, which may largely be explained by differences in approach and by whether physical activity is controlled for. These changes may in turn alter mitochondrial dynamics, such as fusion and fission rates, and mitochondrially induced apoptosis, which may also lead to net muscle fiber loss and age-related sarcopenia. Fortunately, strategies such as exercise and caloric restriction that reduce oxidative damage also improve mitochondrial function. While these strategies may not completely prevent the primary effects of aging, they may help to attenuate the rate of decline. 1. Introduction Around the fourth decade of life, both muscle mass and strength begin to decline [1], and these declines accelerate with advancing age [2]. The loss of muscle mass occurs at a rate of just under 1% per year [3] and appears to be an unavoidable consequence of aging, although it can be slowed by exercise, especially resistance training [4–6]. A significant concern is that as one ages, changes in muscle mass and strength tend to be dissociated. Data from the Baltimore Longitudinal Study of Aging [7] and the Health ABC study [3] showed using DXA and CT that muscle strength declined three times faster than muscle mass, suggesting a decrease in muscle “quality.” This posits that along with an overall reduction in tissue mass, changes are occurring within the skeletal muscle to affect strength. Changes such as accumulation of intra- and extra-myocellular lipids, improper folding of structural and contractile proteins, and mitochondrial dysfunction are thought to occur with age and are the topic of intense scrutiny [8–10]. Dysfunctional mitochondria in particular are thought to play a key role in muscle function decline, as the mitochondria are the main producers of both cellular energy and free radicals. Alterations in mitochondria have

Abstract:
To prospectively demonstrate weight gain in healthy adults, increases body fat [BF], enlarges waist circumference [WC], expands visceral adipose tissue [VAT], exacerbates systemic inflammation [sIF], worsens insulin resistance [IR] and enhances functional cardiovascular disease [CVD] risk.Design, setting and participants: Healthy men [n=11] and women [n=3] provided initial and eight-week post-caloric excess anthropometric and fasting laboratory measures. Functional CVD risk assessments: CBPV and resting EF were also obtained with 7-day automatic ambulatory BP monitoring and increased test finger peripheral arterial tone [PAT] relative to control [reported as relative hyperemia index (RHI)], respectively.Intervention: After determining individualized mean energy requirements for weight maintenance over 7-days, each participant received a personalized over feeding prescription (1.4 times; 41% carbohydrate, 44% fat, and 15% protein) for 8-weeks.mean (SEM). Participants increased body weight [BW + 7.4(0.1) kg]*, body mass index [BMI + 2.5(0.2) kg/m2]*, BF [+2.0(0.01) %]*, WC [+8.2(1.0) cm]*, and VAT [+0.2(0.03) L]* and intrahepatic lipid [IHL + 0.0004(0.002)L] :*all p < 0.01. Increased subcutaneous adipose cell size [+0.3(0.01)rhoL; p = 0.02] accompanied significant sIF [hs-CRP + 0.4(0.09)mg/dL; p = 0.04] and IR [fasting plasma glucose; [FPG] +7.0(0.6)mg/dL;p = 0.01, fasting insulin; [FI] +5.7(1.4)uIU/ml; p = 0.001, HOMA-IR +1.6(0.5); p = 0.02]. Abn CBPV {systolic [+5.4(0.8); p = 0.002, diastolic [+1.7(0.1); p = 0.07 and pulse pressure [PP] [+3.5(0.4); p = 0.003 mm Hg} or elevated heart rate [HR] [+4.9(0.5)bpm; p = 0.003] ensued. Resting RHI declined by 0.47(0.004) from initial 2.24(0.09) to 1.77(0.1); p = 0.001, indicating endothelial dysfunction [ED].Controlled caloric excess in healthy human adults over only 8-weeks significantly increased BF, VAT, sIF [hs-CRP], IR [FPG, FI, HOMA-IR] and functional CVD risk [measured as abnormal circadian blood pressure variability a

Abstract:
The physiologic effects of triiodothyronine (T3) on metabolic rate are well-documented; however, the effects of thyroxine (T4) are less clear despite its wide-spread use to treat thyroid-related disorders and other non-thyroidal conditions. Here, we investigated the effects of acute (3-day) T4 supplementation on energy expenditure at rest and during incremental exercise. Furthermore, we used a combination of in situ and in vitro approaches to measure skeletal muscle metabolism before and after T4 treatment. Ten healthy, euthyroid males were given 200 μg T4 (levothyroxine) per day for 3 days. Energy expenditure was measured at rest and during exercise by indirect calorimetry, and skeletal muscle mitochondrial function was assessed by in situ ATP flux (31P MRS) and in vitro respiratory control ratio (RCR, state 3/state 4 rate of oxygen uptake using a Clark-type electrode) before and after acute T4 treatment. Thyroxine had a subtle effect on resting metabolic rate, increasing it by 4% (p = 0.059) without a change in resting ATP demand (i.e., ATP flux) of the vastus lateralis. Exercise efficiency did not change with T4 treatment. The maximal capacity to produce ATP (state 3 respiration) and the coupled state of the mitochondria (RCR) were reduced by approximately 30% with T4 (p = 0.057 and p = 0.04, respectively). Together, the results suggest that T4, although less metabolically active than T3, reduces skeletal muscle efficiency and modestly increases resting metabolism even after short-term supplementation. Our findings may be clinically relevant given the expanding application of T4 to treat non-thyroidal conditions such as obesity and weight loss.

Abstract:
The no-hair theorem characterizes the fundamental nature of black holes in general relativity. This theorem can be tested observationally by measuring the mass and spin of a black hole as well as its quadrupole moment, which may deviate from the expected Kerr value. Sgr A*, the supermassive black hole at the center of the Milky Way, is a prime candidate for such tests thanks to its large angular size, high brightness, and rich population of nearby stars. In this paper, I discuss a new theoretical framework for a test of the no-hair theorem that is ideal for imaging observations of Sgr A* with very long baseline interferometry (VLBI). The approach is formulated in terms of a Kerr-like spacetime that depends on a free parameter and is regular everywhere outside of the event horizon. Together with the results from astrometric and timing observations, VLBI imaging of Sgr A* may lead to a secure test of the no-hair theorem. 1. Introduction According to the no-hair theorem, black holes are uniquely characterized by their masses and spins and are described by the Kerr metric [1–6]. Mass and spin are the first two multipole moments of the Kerr spacetime, and all higher-order moments can be expressed in terms of these two [7, 8]. The no-hair theorem, then, naturally leads to the expectation that all astrophysical black holes are Kerr black holes. To date, however, a definite proof for the existence of such black holes is still lacking despite a wealth of observational evidence (see discussion in, e.g., [9]). Tests of the no-hair theorem have been suggested using observations in either the gravitational-wave [10–21] or the electromagnetic spectrum [22–31]. Both approaches are based on parametric frameworks that contain one or more free parameters in addition to mass and spin which measure potential deviations from the Kerr metric [18–20, 32–34]. If no deviation is detected, then the compact object is indeed a Kerr black hole. However, since such deviations can have a significant impact on the observed signals, the no-hair theorem may be tested in a twofold manner: if a deviation is measured to be nonzero and if general relativity is assumed, the object cannot be a black hole [18, 35]. Alternatively, if the object is otherwise known to possess an event horizon, it is a black hole, but different from a Kerr black hole. In the latter case, the no-hair theorem would be falsified [22]. Sgr A*, the supermassive black hole at the center of the Milky Way, is a prime target for testing strong-field gravity and the no-hair theorem with electromagnetic observations (see

Abstract:
In a universe of the Randall-Sundrum type, black holes are unstable and emit gravitational modes in the extra dimension. This leads to dramatically shortened lifetimes of astrophysical black holes and to an observable change of the orbital period of black-hole binaries. I obtain an upper limit on the rate of change of the orbital period of the binary XTE J1118+480 and constrain the asymptotic curvature radius of the extra dimension to a value that is of the same order as the constraints from other astrophysical sources. A unique property of XTE J1118+480 is that the expected rate of change of the orbital period due to magnetic braking alone is so large that only one additional measurement of the orbital period would lead to the first detection of orbital evolution of a black-hole binary and impose the tightest constraint to date on the size of one extra dimension of the order of 35 microns.

Abstract:
In a universe of the Randall-Sundrum type, black holes are unstable and emit gravitational modes in the extra dimension. This leads to dramatically shortened lifetimes of astrophysical black holes and to an observable change of the orbital period of black-hole binaries. I obtain an upper limit on the rate of change of the orbital period of the binary XTE J1118+480 and constrain the asymptotic curvature radius of the extra dimension to a value that is of the same order as the constraints from other astrophysical sources. A unique property of XTE J1118+480 is that the expected rate of change of the orbital period due to magnetic braking alone is so large that only one additional measurement of the orbital period would lead to the first detection of orbital evolution of a black-hole binary and impose the tightest constraint to date on the size of one extra dimension of the order of 35 microns.

Abstract:
The spins of a number of supermassive and stellar-mass black holes have been measured based on detections of thermal continuum emission and relativistically broadened iron lines in their x-ray spectra. Likewise, quasiperiodic variability has been observed in several sources. Such measurements commonly make the assumption that black holes are described by the Kerr metric, which according to the no-hair theorem characterizes black holes uniquely in terms of their masses and spins. This fundamental property of black holes can be tested observationally by measuring potential deviations from the Kerr metric introduced by a parametrically deformed Kerr-like spacetime. Thermal spectra, iron lines, and variability have already been studied extensively in several such metrics, which usually depend on only one particular type of deviation or contain unphysical regions outside of the compact object. In this paper, I study these x-ray probes in the background of a new Kerr-like metric which depends on four independent deviation functions and is free of pathological regions outside of the event horizon. I show that the observed signals depend significantly on primarily two types of deviations and that the strong correlation between the spin and the deviation parameters found previously in other Kerr-like metrics is partially broken for rapidly spinning black holes. This suggests that high-spin sources are the best candidates for tests of the no-hair theorem with x-rays and I obtain first constraints on such deviations from the stellar-mass black hole Cygnus X-1.

Abstract:
According to the no-hair theorem, astrophysical black holes are uniquely characterized by their masses and spins and are described by the Kerr metric. Several parametric spacetimes which deviate from the Kerr metric have been proposed in order to test this theorem with observations of black holes in both the electromagnetic and gravitational-wave spectra. Such metrics often contain naked singularities or closed timelike curves in the vicinity of the compact objects that can limit the applicability of the metrics to compact objects that do not spin rapidly, and generally admit only two constants of motion. The existence of a third constant, however, can facilitate the calculation of observables, because the equations of motion can be written in first-order form. In this paper, I design a Kerr-like black hole metric which is regular everywhere outside of the event horizon, possesses three independent constants of motion, and depends nonlinearly on four free functions that parameterize potential deviations from the Kerr metric. This metric is generally not a solution to the field equations of any particular gravity theory, but can be mapped to known four-dimensional black hole solutions of modified theories of gravity for suitable choices of the deviation functions. I derive expressions for the energy, angular momentum, and epicyclic frequencies of a particle on a circular equatorial orbit around the black hole and compute the location of the innermost stable circular orbit. In addition, I write the metric in a Kerr-Schild-like form, which allows for a straightforward implementation of fully relativistic magnetohydrodynamic simulations of accretion flows in this metric. The properties of this metric make it a well-suited spacetime for strong-field tests of the no-hair theorem in the electromagnetic spectrum with black holes of arbitrary spin.

Abstract:
Very-long baseline interferometric observations have resolved structure on scales of only a few Schwarzschild radii around the supermassive black holes at the centers of our Galaxy and M87. In the near future, such observations are expected to image the shadows of these black holes together with a bright and narrow ring surrounding their shadows. For a Kerr black hole, the shape of this photon ring is nearly circular unless the black hole spins very rapidly. Whether or not, however, astrophysical black holes are truly described by the Kerr metric as encapsulated in the no-hair theorem still remains an untested assumption. For black holes that differ from Kerr black holes, photon rings have been shown numerically to be asymmetric for small to intermediate spins. In this paper, I calculate semi-analytic expressions of the shapes of photon rings around black holes described by a new Kerr-like metric which is valid for all spins. I show that photon rings in this spacetime are affected by two types of deviations from the Kerr metric which can cause the ring shape to be highly asymmetric. I argue that the ring asymmetry is a direct measure of a potential violation of the no-hair theorem and that both types of deviations can be detected independently if the mass and distance of the black hole are known. In addition, I obtain approximate expressions of the diameters, displacements, and asymmetries of photon rings around Kerr and Kerr-like black holes.