scholarly journals Contribution of Intramyocellular Lipids to Decreased Computed Tomography Muscle Density With Age

2021 ◽  
Vol 12 ◽  
Author(s):  
Nicholas A. Brennan ◽  
Kenneth W. Fishbein ◽  
David A. Reiter ◽  
Luigi Ferrucci ◽  
Richard G. Spencer
Keyword(s):  
Computed Tomography ◽  
Resonance Spectroscopy ◽  
Older Individuals ◽  
Intramyocellular Lipids ◽  
Muscle Density ◽  
Age Related ◽  
Study Population ◽  
Baltimore Longitudinal Study

Skeletal muscle density, as determined by computed tomography (CT), has been shown to decline with age, resulting in increased frailty and morbidity. However, the mechanism underlying this decrease in muscle density remains elusive. We sought to investigate the role of intramyocellular lipid (IMCL) accumulation in the age-related decline in muscle density. Muscle density was measured using computerized tomography (CT), and IMCL content was quantified using in vivo proton magnetic resonance spectroscopy (1H-MRS). The study population consisted of 314 healthy participants (142 men, 32–98 years) of the Baltimore Longitudinal Study of Aging (BLSA). In addition to IMCL quantification, obesity-related covariates were measured, including body mass index (BMI), waist circumference, and circulating triglyceride concentration. Higher IMCL concentrations were significantly correlated with lower muscle density in older individuals, independent of age, sex, race, and the obesity-associated covariates (p < 0.01). Lower muscle density was also significantly associated with greater age-adjusted IMCL, a variable we constructed using LOESS regression (p < 0.05). Our results suggest that the accumulation of IMCL may be associated with a decrease in muscle density. This may serve to define a potential therapeutic target for treatment of age-associated decreased muscle function.

scholarly journals Lower energy cost of skeletal muscle contractions in older humans

2010 ◽  
Vol 298 (3) ◽  
pp. R729-R739 ◽  
Author(s):  
Michael A. Tevald ◽  
Stephen A. Foulis ◽  
Ian R. Lanza ◽  
Jane A. Kent-Braun
Keyword(s):  
Energy Cost ◽  
Energetic Cost ◽  
Resonance Spectroscopy ◽  
Age Difference ◽  
Force Frequency ◽  
Older Individuals ◽  
Age Related ◽  
Frequency Relationship ◽  
The Cost

Recent studies suggest that the cost of muscle contraction may be reduced in old age, which could be an important mediator of age-related differences in muscle fatigue under some circumstances. We used phosphorus magnetic resonance spectroscopy and electrically elicited contractions to examine the energetic cost of ankle dorsiflexion in 9 young (Y; 26 ± 3.8 yr; mean ± SD) and 9 older healthy men (O; 72 ± 4.6). We hypothesized that the energy cost of twitch and tetanic contractions would be lower in O and that this difference would be greater during tetanic contractions at f50 (frequency at 50% of peak force from force-frequency relationship) than at 25 Hz. The energy costs of a twitch (O = 0.13 ± 0.04 mM ATP/twitch, Y = 0.18 ± 0.06; P = 0.045) and a 60-s tetanus at 25 Hz (O = 1.5 ± 0.4 mM ATP/s, Y = 2.0 ± 0.2; P = 0.01) were 27% and 26% lower in O, respectively, while the respective force·time integrals were not different. In contrast, energy cost during a 90-s tetanus at f50 (O = 10.9 ± 2.0 Hz, Y = 14.8 ± 2.1 Hz; P = 0.002) was 49% lower in O (1.0 ± 0.2 mM ATP/s) compared with Y (1.9 ± 0.2; P < 0.001). Y had greater force potentiation during the f50 protocol, which accounted for the greater age difference in energy cost at f50 compared with 25 Hz. These results provide novel evidence of an age-related difference in human contractile energy cost in vivo and suggest that intramuscular changes contribute to the lower cost of contraction in older muscle. This difference in energetics may provide an important mechanism for the enhanced fatigue resistance often observed in older individuals.

scholarly journals Complement C5 is not critical for the formation of sub-RPE deposits in Efemp1 mutant mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Donita L. Garland ◽  
Eric A. Pierce ◽  
Rosario Fernandez-Godino
Keyword(s):  
Macular Degeneration ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Deposit Formation ◽  
Genetic Ablation ◽  
Age Related ◽  
Complement Dysregulation

AbstractThe complement system plays a role in the formation of sub-retinal pigment epithelial (RPE) deposits in early stages of age-related macular degeneration (AMD). But the specific mechanisms that connect complement activation and deposit formation in AMD patients are unknown, which limits the development of efficient therapies to reduce or stop disease progression. We have previously demonstrated that C3 blockage prevents the formation of sub-RPE deposits in a mouse model of EFEMP1-associated macular degeneration. In this study, we have used double mutant Efemp1R345W/R345W:C5-/- mice to investigate the role of C5 in the formation of sub-RPE deposits in vivo and in vitro. The data revealed that the genetic ablation of C5 does not eliminate the formation of sub-RPE deposits. Contrarily, the absence of C5 in RPE cultures promotes complement dysregulation that results in increased activation of C3, which likely contributes to deposit formation even in the absence of EFEMP1-R345W mutant protein. The results also suggest that genetic ablation of C5 alters the extracellular matrix turnover through an effect on matrix metalloproteinases in RPE cell cultures. These results confirm that C3 rather than C5 could be an effective therapeutic target to treat early AMD.

Neuroimaging for the Clinician

2017 ◽  
Author(s):  
Joshua P Klein
Keyword(s):  
Magnetic Resonance Imaging ◽  
Computed Tomography ◽  
Magnetic Resonance ◽  
Active Role ◽  
Cellular Level ◽  
Vascular Pathology ◽  
Resonance Spectroscopy ◽  
Resonance Imaging ◽  
Spinal Imaging

Modern neuroimaging has revolutionized the practice of neurology by allowing visualization and monitoring of evolving pathophysiologic processes. High-resolution magnetic resonance imaging (MRI) can now resolve structural abnormalities on a near-cellular level. Advances in functional imaging can assess the in vivo metabolic, vascular, and functional states of neuronal and glial populations in real time. Given the high density of data obtained from neuroimaging studies, it is essential for the clinician to take an active role in understanding the nature and significance of imaging abnormalities. This chapter reviews computed tomography and MRI techniques (including angiography and advanced sequences), specialized protocols for investigating specific diagnoses, risks associated with imaging, disease-specific imaging findings with general strategies for interpretation, and incidental findings and artifacts. Figures include computed tomography, T1- and T2-weighted signal intensity, diffusion-weighted magnetic resonance imaging, magnetic resonance spectroscopy, imaging in epilepsy and dementia, extra-axial versus intra-axial lesions, typical lesions of multiple sclerosis, spinal imaging, spinal pathology, vascular pathology, intracranial hemorrhage, and common imaging artifacts. Tables list Hounsfield units, patterns of enhancement from imaging, advanced techniques in imaging, magnetic resonance imaging sequences, and the evolution of cerebral infarction and intraparenchymal hemorrhage on magnetic resonance imaging. This review contains 12 figures, 6 tables, and 213 references.

scholarly journals Decline in rates of clearance of IgG-sensitized erythrocytes with increasing age

Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1726-1730
Author(s):  
KA Melez ◽  
LF Fries ◽  
BS Bender ◽  
T Quinn ◽  
MM Frank
Keyword(s):  
Aging Process ◽  
Elderly Population ◽  
The Elderly ◽  
Older Individuals ◽  
Immune Functions ◽  
Macrophage Function ◽  
Normal Volunteers ◽  
Age Related ◽  
Male Subjects

Decreased immune functions have been suggested as a cause for the increased incidence of autoimmunity, malignancy, and infection in the elderly population. To assess the possible role of changes in macrophage function in the aging process we studied the Fc receptor- mediated clearance of IgG-coated erythrocytes in 56 healthy normal volunteers by following the removal of radiolabeled autologous erythrocytes. An age-related decrease in Fc-mediated clearance rates in both female and male subjects was found, which suggests a physiological decline of this macrophage function in older individuals.

scholarly journals VACCINATION TO PROMOTE HEALTH THROUGHOUT LIFE AS A HEALTHY AGING STRATEGY

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S211-S211
Author(s):  
Leonard Friedland
Keyword(s):  
Immune Response ◽  
Healthy Aging ◽  
New Technologies ◽  
Older Age ◽  
Target Antigen ◽  
Older Individuals ◽  
Demographic Shift ◽  
Age Related ◽  
Important Progress

Abstract This symposium addresses the role of vaccination to promote healthy aging, the process of developing and maintaining the functional ability that enables wellbeing in older age. Life-span immunization of adults across all age categories can help to reduce morbidity and mortality. Healthy aging is critical for our global society to counter the surge in healthcare costs that is coming as a result of the demographic shift to older age. Immune system function and response to vaccination declines with advancing age. Generating effective immune responses against new infectious disease targets can be difficult in older individuals. Important progress has been made in understanding the mechanisms underlying immunosenescence, the age-related decline of the immune response to infections and vaccinations. Innovative research and the development of new technologies, such as adjuvants, substances that can enhance and shape the immune response to the target antigen(s), has facilitated the development of vaccines specially tailored for adults. This evidence-based approach to the development of innovative vaccines addressing immunosenescence is an important clinically relevant healthy aging strategy to promote health throughout life.

scholarly journals Human skeletal muscle metabolic economy in vivo: effects of contraction intensity, age, and mobility impairment

2014 ◽  
Vol 307 (9) ◽  
pp. R1124-R1135 ◽  
Author(s):  
Anita D. Christie ◽  
Anne Tonson ◽  
Ryan G. Larsen ◽  
Jacob P. DeBlois ◽  
Jane A. Kent
Keyword(s):  
Functional Mobility ◽  
Older Individuals ◽  
Mobility Impairment ◽  
Cross Sectional ◽  
Age Related ◽  
Creatine Kinase Reaction ◽  
Voluntary Contractions ◽  
In Vivo Effects ◽  
Muscle Cross Sectional Area

We tested the hypothesis that older muscle has greater metabolic economy (ME) in vivo than young, in a manner dependent, in part, on contraction intensity. Twenty young (Y; 24 ± 1 yr, 10 women), 18 older healthy (O; 73 ± 2, 9 women) and 9 older individuals with mild-to-moderate mobility impairment (OI; 74 ± 1, 7 women) received stimulated twitches (2 Hz, 3 min) and performed nonfatiguing voluntary (20, 50, and 100% maximal; 12 s each) isometric dorsiflexion contractions. Torque-time integrals (TTI; Nm·s) were calculated and expressed relative to maximal fat-free muscle cross-sectional area (cm2), and torque variability during voluntary contractions was calculated as the coefficient of variation. Total ATP cost of contraction (mM) was determined from flux through the creatine kinase reaction, nonoxidative glycolysis and oxidative phosphorylation, and used to calculate ME (Nm·s·cm−2·mM ATP−1). While twitch torque relaxation was slower in O and OI compared with Y ( P ≤ 0.001), twitch TTI, ATP cost, and economy were similar across groups ( P ≥ 0.15), indicating comparable intrinsic muscle economy during electrically induced isometric contractions in vivo. During voluntary contractions, normalized TTI and total ATP cost did not differ significantly across groups ( P ≥ 0.20). However, ME was lower in OI than Y or O at 20% and 50% MVC ( P ≤ 0.02), and torque variability was greater in OI than Y or O at 20% MVC ( P ≤ 0.05). These results refute the hypothesis of greater muscle ME in old age, and provide support for lower ME in impaired older adults as a potential mechanism or consequence of age-related reductions in functional mobility.

Biaxial Mechanical Testing of Single Annulus Fibrosus Layers

2010 ◽  
Author(s):  
J. P. Rys ◽  
A. M. Ellingson ◽  
D. J. Nuckley ◽  
V. H. Barocas
Keyword(s):  
Intervertebral Disc ◽  
Annulus Fibrosus ◽  
Spinal Nerve ◽  
Older Individuals ◽  
Physical Trauma ◽  
Age Related ◽  
Biaxial Mechanical Testing ◽  
Partial Displacement ◽  
Outer Annulus Fibrosus

The intervertebral disc (IVD), consisting of the inner nucleus pulposus and the outer annulus fibrosus, is subjected to multiaxial stress in vivo. The disc undergoes degenerative changes that account for impairment and disability in middle-aged and older individuals.4 In addition to age-related degeneration, the intervertebral disc is subject to the development of lesions due to partial displacement or rupture of the annulus fibrosus. Such occurrences, typically resulting from physical trauma, can yield disabling effects from impingement on spinal nerve structures. A greater understanding of the IVD and how it functions mechanically is crucial in prevention and repair of debilitating spinal disorders.

scholarly journals Archives of General Psychiatry, June 1991

1991 ◽  
Vol 15 (12) ◽  
pp. 738-739 ◽  
Author(s):  
Robert Kerwin ◽  
Paul Bailey
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Second Messenger ◽  
Resonance Spectroscopy ◽  
General Psychiatry ◽  
Second Messenger Systems ◽  
Neurobiological Research ◽  
High Standards

We were recently asked by one of the editors of the Psychiatric Bulletin to comment on the June 1991 issue of the Archives of General Psychiatry because of its exclusive neurobiological approach that month. Having thus been given our brief and now having carefully read the issue, we feel obliged to warmly congratulate the Archives for a superb issue and a superb Journal that has consistently set high standards for the reporting of neurobiological research as applied to psychiatry. The June issue this year was the first to report the use of magnetic resonance spectroscopy (as opposed to imaging) in vivo (more of this later) and had many more excellent contributions on the action of lithium on neurotransmiter and second messenger systems and papers on the role of serotonin and endorphins in a variety of conditions.

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