Melatonin Alleviates Liver Mitochondrial Dysfunction in Leptin-Deficient Mice.

Despite efforts to elucidate the cellular adaptations induced by obesity, cellular bioenergetics is currently considered a crucial target. New strategies to delay the onset of the hazardous adaptations induced by obesity are needed. Therefore, we evaluated the effects of 4 weeks of melatonin treatment on mitochondrial function and lipid metabolism in the livers of leptin-deficient mice.

p66Shc signaling and autophagy impact on C2C12 myoblast differentiation during senescence.

During aging, muscle regenerative capacities decline, which is concomitant with the loss of satellite cells that enter in a state of irreversible senescence. However, what mechanisms are involved in myogenic senescence and differentiation are largely unknown. Here, we showed that early-passage or "young" C2C12 myoblasts activated the redox-sensitive p66Shc signaling pathway, exhibited a strong antioxidant protection and a bioenergetic profile relying predominantly on OXPHOS, responses that decrease progressively during differentiation.

Melatonin Alleviates the Impairment of Muscle Bioenergetics and Protein Quality Control Systems in Leptin-Deficiency-Induced Obesity.

Leptin is critically compromised in the major common forms of obesity. Skeletal muscle is the main effector tissue for energy modification that occurs as a result of the effect of endocrine axes, such as leptin signaling. Our study was carried out using skeletal muscle from a leptin-deficient animal model, in order to ascertain the importance of this hormone and to identify the major skeletal muscle mechanisms affected.

Inflammaging: Implications in Sarcopenia.

In a world in which life expectancy is increasing, understanding and promoting healthy aging becomes a contemporary demand. In the elderly, a sterile, chronic and low-grade systemic inflammation known as "inflammaging" is linked with many age-associated diseases. Considering sarcopenia as a loss of strength and mass of skeletal muscle related to aging, correlations between these two terms have been proposed.

Chronic Treatment with Melatonin Improves Hippocampal Neurogenesis in the Aged Brain and Under Neurodegeneration.

Adult hippocampal neurogenesis is altered during aging and under different neuropsychiatric and neurodegenerative diseases. Melatonin shows neurogenic and neuroprotective properties during aging and neuropathological conditions. In this study, we evaluated the effects of chronic treatment with melatonin on different markers of neurodegeneration and hippocampal neurogenesis using immunohistochemistry in the aged and neurodegenerative brains of SAMP8 mice, which is an animal model of accelerated senescence that mimics aging-related Alzheimer's pathology.

Cell interactome in sarcopenia during aging.

Background: The diversity between the muscle cellular interactome of dependent and independent elderly people is based on the interrelationships established between different cellular mechanisms, and alteration of this balance modulates cellular activity in muscle tissue with important functional implications.

Methods: Thirty patients (85 ± 8 years old, 23% female) scheduled to undergo hip fracture surgery participated in this study. During the surgical procedures, skeletal muscle tissue was obtained from the Vastus lateralis.

The Interactome in the Evolution From Frailty to Sarcopenic Dependence.

Biomarkers are essential tools for accurate diagnosis and effective prevention, but their validation is a pending challenge that limits their usefulness, even more so with constructs as complex as frailty. Sarcopenia shares multiple mechanisms with frailty which makes it a strong candidate to provide robust frailty biomarkers. Based on this premise, we studied the temporal evolution of cellular interactome in frailty, from independent patients to dependent ones.

Neurogenic Potential of the 18-kDa Mitochondrial Translocator Protein (TSPO) in Pluripotent P19 Stem Cells.

The 18-kDa translocator protein (TSPO) is a key mitochondrial target by which different TSPO ligands exert neuroprotective effects. We assayed the neurogenic potential of TSPO to induce the neuronal differentiation of pluripotent P19 stem cells in vitro. We studied changes in cell morphology, cell proliferation, cell death, the cell cycle, mitochondrial functionality, and the levels of pluripotency and neurogenesis of P19 stem cells treated with the TSPO ligand, PK 11195, in comparison to differentiation induced by retinoid acid (RA) and undifferentiated P19 stem cells.

Prognostic networks for unraveling the biological mechanisms of Sarcopenia.

Sarcopenia is an age-related multifactorial process that involved several biological mechanisms, whose specific contribution and interplay is still unknown. The present study proposes prognostic networks based on machine learning approaches to unravel the interplay among those biological mechanisms mainly involved in the development of Sarcopenia. After analyzing 114 biological and clinical variables in adults older than 70 years, and using all the biological prognostic networks detected by machine learning with accuracy higher than 82%, we designed a consensus classifier based on majority vote that improve the predictive accuracy of Sarcopenia up to 91%.

Overweight in the Elderly Induces a Switch in Energy Metabolism that Undermines Muscle Integrity.

Aging is characterized by a progressive loss of skeletal muscle mass and function (sarcopenia). Obesity exacerbates age-related decline and lead to frailty. Skeletal muscle fat infiltration increases with aging and seems to be crucial for the progression of sarcopenia.

Cell quality control mechanisms maintain stemness and differentiation potential of P19 embryonic carcinoma cells.

Given the relatively long life of stem cells (SCs), efficient mechanisms of quality control to balance cell survival and resistance to external and internal stress are required. Our objective was to test the relevance of cell quality control mechanisms for SCs maintenance, differentiation and resistance to cell death. We compared cell quality control in P19 stem cells (P19SCs) before and after differentiation (P19dCs).

High-Fructose Consumption Impairs the Redox System and Protein Quality Control in the Brain of Syrian Hamsters: Therapeutic Effects of Melatonin.

Although numerous studies have demonstrated the harmful effect of excessive fructose consumption at the systemic level, there is little information on its effects in the central nervous system. The purpose of the present work was to study the cellular alterations related to oxidative stress and protein quality control systems induced by a high-fructose diet in the brain of Syrian hamsters and their possible attenuation by exogenous melatonin. High-fructose intake induced type II diabetes together with oxidative damage, led to alterations of the unfolded protein response by activating the eIF2α branch, and impaired the macroautophagic machinery in the brain, favoring the accumulation of aggregates labeled for selective degradation and neurodegeneration markers such as β-amyloid (1-42), tau-p-S199, and tau-p-S404.

Melatonin Prevents the Harmful Effects of Obesity on the Brain, Including at the Behavioral Level.

Obesity is a health problem caused by a diet rich in energy and the sedentary lifestyle of modern societies. A leptin deficiency is one of the worst causes of obesity, since it results in morbid obesity, a chronic disease without a cure. Leptin is an adipokine secreted in a manner dependent on the circadian rhythm that ultimately reduces food intake.