Diet-Modifiable Redox Alterations in Ageing and Cancer.

With ageing comes some of life's best and worst moments. Those lucky enough to live out into the seventh, eighth, and nineth decades and perhaps beyond have more opportunities to experience the wonders and joys of the world. As the world's population shifts towards more and more of these individuals, this is something to be celebrated.

Entanglements of Technologies, Agency and Selfhood: Exploring the Complexity in Attitudes Toward Mental Health Chatbots.

Whilst chatbots for mental health are becoming increasingly prevalent, research on user experiences and expectations is relatively scarce and also equivocal on their acceptability and utility. This paper asks how people formulate their understandings of what might be appropriate in this space. We draw on data from a group of non-users who have experienced a need for support, and so can imagine self as therapeutic target-enabling us to tap into their imaginative speculations of the self in relation to the chatbot other and the forms of agency they see as being at play; unconstrained by a specific actual chatbot.

Should I stay or should I go? Transsulfuration influences invasion and growth in glioblastoma.

A major challenge in treating patients with glioblastoma is the inability to eliminate highly invasive cells with chemotherapy, radiation, or surgical resection. As cancer cells face the issue of replicating or invading neighboring tissue, they rewire their metabolism in a concerted effort to support necessary cellular processes and account for altered nutrient abundance. In this issue of the JCI, Garcia et al.

HS serves as the immunoregulatory essence of apoptotic cell death.

Apoptosis supports tissue homeostasis and prevents immune disorders by removing damaged and functionally aberrant cells. Here, Ou et al. utilized genetic, pharmacological, and proteomic approaches focused on sulfur amino acid catabolism to discover that hydrogen sulfide (HS) release during apoptosis suppresses Th17 cell differentiation, thus providing therapeutic targets for autoimmune diseases.

A long-term obesogenic high-fat diet in mice partially dampens the anti-frailty benefits of late-life intermittent fasting.

The global obesity pandemic coupled with ever-growing life expectancies equates to hundreds of millions of individuals with potentially longer but not healthier lives. Aging is one of the risk factors for numerous maladies such as metabolic disorder and frailty, which are exacerbated under obesity. Thus, therapeutic approaches that address obesity to ultimately improve affected individuals' quality of life and extend their lifespan are needed.

A systematic review of lung clearance index in non-cystic fibrosis, non-primary ciliary dyskinesia bronchiectasis.

Background: Non cystic fibrosis, non primary ciliary dyskinesia bronchiectasis (nCFnPCD-BE) results in significant morbidity with few evidence-based treatments.

Objective: assessments are required to assess severity and evaluate treatment. Lung clearance index (LCI) measures ventilation inhomogeneity and is a sensitive test of disease in CF; its use in nCFnPCD-BE is unclear.

Stable isotope dilution mass spectrometry quantification of hydrogen sulfide and thiols in biological matrices.

Background: Hydrogen sulfide (HS), a gaseous signaling molecule that impacts multiple physiological processes including aging, is produced via select mammalian enzymes and enteric sulfur-reducing bacteria. HS research is limited by the lack of an accurate internal standard-containing assay for its quantitation in biological matrices.

Methods: After synthesizing [S]HS and developing sample preparation protocols that avoid sulfide contamination with the addition of thiol-containing standards or reducing reagents, we developed a stable isotope-dilution high performance liquid chromatography tandem-mass spectrometry (LC-MS/MS) method for the simultaneous quantification of Total HS and other abundant thiols (cysteine, homocysteine, glutathione, glutamylcysteine, cysteinylglycine) in biological matrices, conducted a 20-day analytical validation/normal range study, and then both analyzed circulating Total HS and thiols in plasma from 400 subjects, and within 20 volunteers before and after antibiotic-induced suppression of gut microbiota.

Who are the 10%? - Non eligibility of cystic fibrosis (CF) patients for highly effective modulator therapies.

Background: The availability of mutation-specific cystic fibrosis modulator therapies has the potential to improve the lives of children and adults with cystic fibrosis. The frequency of mutations causing defects in the cystic fibrosis transmembrane conductance regulator (CFTR) function varies between sub-groups in multi-ethnic populations. The profile of patients eligible for CFTR modulator ivacaftor/tezacaftor/elexacaftor (Kaftrio™) therapy based on ethnicity has not been reported in the United Kingdom CF population.

Sulfur Amino Acid Supplementation Abrogates Protective Effects of Caloric Restriction for Enhancing Bone Marrow Regrowth Following Ionizing Radiation.

Radiation therapy damages and depletes total bone marrow (BM) cellularity, compromising safety and limiting effective dosing. Aging also strains total BM and BM hematopoietic stem and progenitor cell (HSPC) renewal and function, resulting in multi-system defects. Interventions that preserve BM and BM HSPC homeostasis thus have potential clinical significance.

Ethical considerations in design and implementation of home-based smart care for dementia.

It has now become a realistic prospect for smart care to be provided at home for those living with long-term conditions such as dementia. In the contemporary smart care scenario, homes are fitted with an array of sensors for remote monitoring providing data that feed into intelligent systems developed to highlight concerning patterns of behaviour or physiological measurements and to alert healthcare professionals to the need for action. This paper explores some ethical issues that may arise within such smart care systems, focusing on the extent to which ethical issues can be addressed at the system design stage.

Early DNA damage detection and cellular autophagy as drivers of stress-adaptive HS production: A paradox resolved.

Appropriately responding and adapting to genotoxic, oxidative, and metabolic stress is essential for survival and is at the heart of maintaining homeostasis. In this issue of Cell Chemical Biology, Jiang et al. (2021) describe an autophagy-dependent mechanism for cytoprotective HS generation initiated by DNA damage and other small molecule treatments.

Plasma Hydrogen Sulfide Is Positively Associated With Post-operative Survival in Patients Undergoing Surgical Revascularization.

Hydrogen sulfide (HS) is a gaseous signaling molecule and redox factor important for cardiovascular function. Deficiencies in its production or bioavailability are implicated in atherosclerotic disease. However, it is unknown if circulating HS levels differ between vasculopaths and healthy individuals, and if so, whether HS measurements can be used to predict surgical outcomes.

Hydrogen sulfide operates as a glioblastoma suppressor and is lost under high fat diet.

Glioblastoma (GBM) is one of the deadliest and aggressive forms of brain cancer. Environmental and intrinsic factors such as Western Diet and advanced age can function as powerful accelerants to the progression of GBM. Recently, we discovered that pre-clinical GBM models subject to an obesogenic and age-accelerating high fat diet (HFD) presented with hyperaggressive GBM phenotypes, including treatment-refractory cancer stem cell (CSC) enrichment.

The naked truth: a comprehensive clarification and classification of current 'myths' in naked mole-rat biology.

The naked mole-rat (Heterocephalus glaber) has fascinated zoologists for at least half a century. It has also generated considerable biomedical interest not only because of its extraordinary longevity, but also because of unusual protective features (e.g.

Peripubertal Bisphenol A Exposure Imparts Detrimental Age-Related Changes in Body Composition, Cognition, and Hydrogen Sulfide Production Capacities.

Peripubertal endocrine disruption has immediate and lifelong consequences on health, cognition, and lifespan. Disruption comes from dietary, environmental, and pharmaceutical sources. The plasticizer Bisphenol A (BPA) is one such endocrine disrupting chemical.

Severe consequences of a high-lipid diet include hydrogen sulfide dysfunction and enhanced aggression in glioblastoma.

Glioblastoma (GBM) remains among the deadliest of human malignancies, and the emergence of the cancer stem cell (CSC) phenotype represents a major challenge to durable treatment response. Because the environmental and lifestyle factors that impact CSC populations are not clear, we sought to understand the consequences of diet on CSC enrichment. We evaluated disease progression in mice fed an obesity-inducing high-fat diet (HFD) versus a low-fat, control diet.

Dietary restriction transforms the mammalian protein persulfidome in a tissue-specific and cystathionine γ-lyase-dependent manner.

Hydrogen sulfide (HS) is a cytoprotective redox-active metabolite that signals through protein persulfidation (R-SSH). Despite the known importance of persulfidation, tissue-specific persulfidome profiles and their associated functions are not well characterized, specifically under conditions and interventions known to modulate HS production. We hypothesize that dietary restriction (DR), which increases lifespan and can boost HS production, expands tissue-specific persulfidomes.

Late-life intermittent fasting decreases aging-related frailty and increases renal hydrogen sulfide production in a sexually dimorphic manner.

Global average life expectancy continues to rise. As aging increases the likelihood of frailty, which encompasses metabolic, musculoskeletal, and cognitive deficits, there is a need for effective anti-aging treatments. It is well established in model organisms that dietary restriction (DR), such as caloric restriction or protein restriction, enhances health and lifespan.

Physiologic Responses to Dietary Sulfur Amino Acid Restriction in Mice Are Influenced by Atf4 Status and Biological Sex.

Background: Dietary sulfur amino acid restriction (SAAR) improves body composition and metabolic health across several model organisms in part through induction of the integrated stress response (ISR).

Objective: We investigate the hypothesis that activating transcription factor 4 (ATF4) acts as a converging point in the ISR during SAAR.

Methods: Using liver-specific or global gene ablation strategies, in both female and male mice, we address the role of ATF4 during dietary SAAR.

Conversational agents and the making of mental health recovery.

Background: Artificial intelligence (AI) is said to be "transforming mental health". AI-based technologies and technique are now considered to have uses in almost every domain of mental health care: including decision-making, assessment and healthcare management. What remains underexplored is whether/how mental health is situated within these discussions and practices.

Reproductive Longevity and Aging: Geroscience Approaches to Maintain Long-Term Ovarian Fitness.

Increases in delayed childbearing worldwide have elicited the need for a better understanding of the biological underpinnings and implications of age-related infertility. In women 35 years and older the incidences of infertility, aneuploidy, and birth defects dramatically increase. These outcomes are a result of age-related declines in both ovarian reserve and oocyte quality.

IL-1 induces mitochondrial translocation of IRAK2 to suppress oxidative metabolism in adipocytes.

Chronic inflammation is a common feature of obesity, with elevated cytokines such as interleukin-1 (IL-1) in the circulation and tissues. Here, we report an unconventional IL-1R-MyD88-IRAK2-PHB/OPA1 signaling axis that reprograms mitochondrial metabolism in adipocytes to exacerbate obesity. IL-1 induced recruitment of IRAK2 Myddosome to mitochondria outer membranes via recognition by TOM20, followed by TIMM50-guided translocation of IRAK2 into mitochondria inner membranes, to suppress oxidative phosphorylation and fatty acid oxidation, thereby attenuating energy expenditure.