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Mitochondria are crucial cellular organelles that regulate energy production, oxidative balance, and calcium homeostasis, among other things. Aging is a natural, multifactorial, and multi-organic process, in which both pathological and physiological changes occur gradually over time. Autophagy capacity and mitochondrial processes such as mitophagy, biogenesis, and dynamics are associated with aging. These processes are important for maintaining the structural integrity of mitochondria and thus cell life since mitochondrial dysfunction leads to an impairment in energy metabolism and an increased production of reactive oxygen species, both of which may stimulate mechanisms of cellular senescence and apoptotic cell death. Furthermore, in both model organisms and humans, a decline in mitochondrial activity can contribute to age-related disease phenotypes. As people age, mitochondrial damage and malfunction may induce apoptosis, thus explaining the rise in cell death. Many aging processes are believed to be driven by oxidative stress. Taken together, the evidence strongly suggests a relation between mitochondrial function and a wide spectrum of aging processes. Although there is no general consensus among the studies reviewed, it appears that aging reduces mitochondrial biogenesis and dynamics, as well as the mitophagy capacity of the organism involved. This review describes the involvement of autophagy and apoptosis in the modulation of mitochondrial function in the brain.

Background: As people age, physical impairments may have a deleterious role in skeletal muscles. Sarcopenia Clinical Practice Guidelines 2017 and the European Working Group on Sarcopenia in older people are two organizations that have published essential guidelines on the definition of “sarcopenia". Sarcopenia is a geriatric syndrome, characterized by skeletal muscle mass degeneration brought on by ageing, which lowers muscular function and quality. Moreover, sarcopenia can be classified as primary or age-associated sarcopenia and secondary sarcopenia. Also, secondary sarcopenia occurs when other diseases such as diabetes, obesity, cancer, cirrhosis, myocardial failure, chronic obstructive pulmonary disease, and inflammatory bowel disease also contribute to muscle loss. Furthermore, sarcopenia is linked with a high risk of negative outcomes, considering a gradual reduction in physical mobility, poor balance, and increased fracture risks which ultimately leads to poor quality of life. Objective: In this comprehensive review, we have elaborated on the pathophysiology, and various signaling pathways linked with sarcopenia. Also, discussed are the preclinical models and current interventional therapeutics to treat muscle wasting in older patients. Conclusion: In a nutshell, a comprehensive description of the pathophysiology, mechanisms, animal models, and interventions of sarcopenia. We also shed light on pharmacotherapeutics present in clinical trials which are being developed as potential therapeutic options for wasting diseases. Thus, this review could fill in the knowledge gaps regarding sarcopenia-related muscle loss and muscle quality for both researchers and clinicians.

Obstruct pharmacokinetics and low bioavailability of diosgenin (DG) and emodin (ED) are major limitations for their therapeutic success in several inflammatory diseases. Nanoencapsulation of both drugs will promisingly overcome these limitations. Herein, polylactic-co-glycolic acid (PLGA) was used for nanoformulation of diosgenin and emodin-loaded PLGA nanoparticle (DGn and EDn) via modified solvent-emulsion-diffusion-evaporation method. Functional stability of prepared nanoparticles and in vitro physiological characterization including mean particle sizes distribution, polydispersity index, surface zeta potential, and morphological examinations were performed. Moreover, drug loading and encapsulation efficiency were also evaluated by measuring drug concentration through spectroscopy and HPLC method. Both drug nanoformulations demonstrated functional drug stability, 200─270 nm sizes with homogeneous particle distribution, negative surface zeta potential stability, and uniform spherical morphology. Moreover, nanoparticles showed in vitro controlled drug release pattern over 24 hours with 40─70% of drug depletion. Pharmacokinetics analysis was performed on sixteen rats equally distributed in four groups (DG, ED, DGn, and EDn). Pure drugs and nanoformulations were orally (10 mg/kg) administrated to animal model, and pharmacokinetic profiles of both drugs were evaluated. PLGA nanoparticles were significantly able to alter the pharmacokinetics of DG, while little improvement was observed for ED. Consequently, changes in pharmacokinetics of both drugs are attributed to size and surface characteristics of nanoparticles. DGn and EDn subsidize increased mean plasma residence time and maximize area under curve with decreased drug clearance rate. Resulting in vitro characteristics and in vivo pharmacokinetics data reveal the efficacy of DGn and EDn to be suitable nano-drug delivery modalities with improved bioavailability and pharmacological strength.

Antipsychotic-induced obesity affects millions of people and is a serious health condition worldwide. Olanzapine is the most widely prescribed antipsychotic agent with high obesogenic potential. However, the exact mechanism by which it causes its metabolic dysregulation remains poorly understood. In this study, we investigated the effect of agmatine in olanzapine-induced metabolic derangements in Female Sprague-Dawley rats. Repeated olanzapine administration for 28 days increased body weight while treatment with agmatine from days 15 to 28 prevented the body weight gain induced by olanzapine without any alteration in food intake. Repeated agmatine treatment decreased the elevated feeding efficiency and adiposity index, as well as improved dysregulated lipid metabolism induced by olanzapine. Increased activity of fatty acid synthase (FAS) and decreased expression of carnitine palmitoyl transferase-1 (CPT-1) were detected in chronic olanzapine-treated rats. Although agmatine treatment did not alter FAS activity, it increased CPT-1 activity. It is possible that the inhibitory effect of agmatine on weight gain and adiposity might be associated with increased mitochondrial fatty acid oxidation and energy expenditure in olanzapine-treated rats. We suggest that agmatine can be explored for the prevention of obesity complications associated with chronic antipsychotic treatment.