The increasing global aging population has brought greater focus to age-related diseases, particularly muscle-brain comorbidities such as sarcopenia and late-life depression. Sarcopenia, defined by the gradual loss of muscle mass and function, is notably prevalent among older individuals, while late-life depression profoundly affects their mental health and overall well-being. Epidemiological evidence suggests a high co-occurrence of these two conditions, although the precise biological mechanisms linking them remain inadequately understood. This review synthesizes the existing body of literature on sarcopenia and late-life depression, examining their definitions, prevalence, clinical presentations, and available treatments. The goal is to clarify the potential connections between these comorbidities and offer a theoretical framework for the development of future preventive and therapeutic strategies.

Sarcopenia and AD are both classic degenerative diseases, and there is growing epidemiological evidence of their comorbidity with aging; however, the mechanisms underlying the biology of their commonality have not yet been thoroughly investigated. APP is a membrane protein that is expressed in tissues and is expressed not only in the nervous system but also in the NMJ and muscle. Deposition of its proteolytic cleavage product, Aβ, has been described as a central component of AD pathogenesis. Recent studies have shown that excessive accumulation and aberrant expression of APP in muscle lead to pathological muscle lesions, but the pathogenic mechanism by which APP and its proteolytic cleavage products act in skeletal muscle is less well understood. By summarizing and analyzing the literature concerning the role, pathogenicity and pathological mechanisms of APP and its cleavage products in the nervous system and muscles, we aimed to explore the intrinsic pathological mechanisms of myocerebral comorbidities and to provide new perspectives and theoretical foundations for the prevention and treatment of AD and sarcopenia comorbidities.

Sarcopenic obesity, characterized by skeletal muscle loss concurrent with adipose tissue accumulation, has emerged as a global health threat. Exercise is established as an effective intervention; however, the molecular mechanisms underlying its protective effects remain incompletely defined. This study investigated whether exercise mitigates high-fat diet (HFD)-induced sarcopenic obesity, and whether the mechanism was related to the activation of the adenosine monophosphate-activated protein kinase (AMPK)/Acetyl-CoA carboxylase pathway (ACC) pathway and the inhibition of ferroptosis. Cell experiments demonstrated that palmitic acid induced ferroptosis in C2C12 mouse myoblasts. Animal experiments confirmed that HFD promoted skeletal muscle ferroptosis in C57BL/6 mice, evidenced by iron metabolism imbalance (solute carrier family 39 member14 upregulation, ferroportin downregulation), impaired antioxidant capacity (reduced glutathione, superoxide dismutase, glutathione peroxidase 4), and elevated lipid peroxidation (increased malondialdehyde). Meanwhile, both flat treadmill running and uphill treadmill running may reverse these changes by activating AMPK/ACC phosphorylation, reducing non-transferrin iron uptake, enhancing iron export and storage, and improving antioxidant status, jointly inhibiting ferroptosis and attenuating muscle mass loss and lipid deposition. These findings confirm that ferroptosis acts as one of the key pathogenic drivers in sarcopenic obesity and suggests that exercise may improve sarcopenic obesity by activating the AMPK/ACC pathway and inhibiting ferroptosis. This study provides novel mechanistic insights into exercise-mediated regulation of iron-lipid metabolism crosstalk and informs targeted interventions for sarcopenic obesity.

Neurodegenerative diseases (e.g., Alzheimer's disease [AD], Parkinson's disease [PD], Huntington's disease [HD]) pose a serious threat to human health. Current therapeutic approaches have limitations such as significant side effects and limited efficacy, making natural plant active ingredients an emerging research focus in this field. Solanaceae plants are widely distributed worldwide, rich in secondary metabolites such as alkaloids and flavonoids, and have long been used in traditional medicine. This review systematically summarizes the structural characteristics of Solanaceae-derived alkaloids (e.g., nicotine[NI], atropine[ATP], scopolamine[SCO]) and flavonoids (e.g., quercetin[QR], luteolin[LUT], kaempferol[KAE], anthocyanidin[ACN]), as well as their therapeutic potential and core mechanisms of action against the three major neurodegenerative diseases - including multi-target regulatory pathways such as antioxidative stress, inhibiting neuroinflammation, regulating neurotransmitter balance, preventing abnormal protein aggregation, and suppressing neuronal apoptosis. Additionally, this review analyzes the challenges faced by these natural products in extraction and purification, bioavailability, target selectivity, and clinical translation, and prospects the potential of promoting their clinical application through technological breakthroughs such as synthetic biology and nanodelivery systems. This review indicates that Solanaceae-derived secondary metabolites provide an important resource for the development of safe and effective therapeutic drugs for neurodegenerative diseases, with broad application value.

Alcohol enters the brain through the blood–brain barrier and causes neuronal damage in various ways, additionally long-term and heavy drinking also leads to both structural and functional changes in the central nervous system. Currently, there is a lack of specific therapeutic approaches for alcohol-induced nerve injury. Opuntia milpa alta polysaccharides (MAPs) have various physiological activities such as antioxidant, anti-inflammatory, and neuroprotective effects, but it is not clear how they protect against alcohol-induced nerve injury. In this study, firstly, we structurally characterized homemade MAPs and analyzed the relevance of MAPs in protecting against alcoholic neuronal cell injury and ferroptosis. The results showed that MAPs consisted of nine different monosaccharides and uronic acids. High performance gel permeation chromatography analysis showed that MAPs were homogeneous heteropolysaccharides with an average molecular weight of 8.79 × 106 Da. Fourier infrared spectroscopy showed that they had sulfated pyranopolysaccharides with uronic acids and both α-glycosidic and β-glycosidic bonds were present. Specific signals of these sugars were observed in 1H and 13C NMR spectra. Favorable thermal stability was manifested up to 256 °C. The MAPs had a three-stranded helical structure and a low overall crystallinity. Iron staining showed that alcohol caused significant brown deposition in cells. MAPs significantly ameliorated alcohol-induced cellular damage, reduced iron deposition, and orchestrated the expression of proteins associated with ferroptosis. These results suggest that MAPs protect against alcohol-induced neurological damage, possibly by impeding the onset of cellular ferroptosis.