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To gain insight into how researchers of aging perceive the process they study, we conducted a survey among experts in the field. While highlighting some common features of aging, the survey exposed broad disagreement on the foundational issues. What is aging? What causes it? When does it begin? What constitutes rejuvenation? Not only was there no consensus on these and other core questions, but none of the questions received a majority opinion-even regarding the need for consensus itself. Despite many researchers believing they understand aging, their understanding diverges considerably. Importantly, as different processes are labeled as "aging" by researchers, different experimental approaches are prioritized. The survey shed light on the need to better define which aging processes this field should target and what its goals are. It also allowed us to categorize contemporary views on aging and rejuvenation, revealing critical, yet largely unanswered, questions that appear disconnected from the current research focus. Finally, we discuss ways to address the disagreement, which we hope will ultimately aid progress in the field., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Background: The Pacific Island country of Vanuatu is at the early stages of demographic ageing. The government is yet to develop a strategic approach to optimize the health and wellbeing of older indigenous Vanuatu residents (ni-Vanuatu)., Methods: Using policy mapping and semi-structured interviews with 42 ni-Vanuatu, this research aimed to explore the current policy context surrounding ageing in Vanuatu and the priorities of older adults to inform preliminary steps to develop a national response to healthy ageing. Analyses were grounded in the World Health Organization's Regional Action Plan on Healthy Ageing in the Western Pacific ., Findings: While the national policy context exhibited an indirect commitment to creating an environment conducive to healthy ageing, explicit policy commitments and monitoring indicators were lacking. Older persons reported numerous obstacles to healthy ageing, including financial insecurity, physical and psychological barriers to participation, and lack of community support., Interpretation: Findings highlighted the need for policymakers and stakeholders to focus preliminary strategic efforts on select components of the Regional Action Plan: evidence generation, advocacy/awareness, financing, community engagement and coordination, and family-centred empowerment. To ensure acceptability and sustainability, it is vital that these leverage existing strengths of traditional community values and the prevailing role of faith and religion in the lives of older ni-Vanuatu., Funding: This project was funded and supported by the World Health Organization (WHO) Regional Office for the Western Pacific (WPRO). Outcomes reflect the deliberations of authors and research partners., Competing Interests: None declared., (© 2024 World Health Organization.)

Small fractions of patients suffer from radiotherapy late severe adverse events (AEs Grade ≥ 3), which are usually irreversible and badly affect their quality of life. A novel functional DNA repair assay characterizing several steps of double-strand break (DSB) repair mechanisms was used. DNA repair activities of peripheral blood mononuclear cells were monitored for 1 week using NEXT-SPOT assay in 177 breast and prostate cancer patients. Only seven patients had Grade ≥ 3 AEs, 6 months after radiotherapy initiation. The machine learning method established the importance of variables among demographic, clinical and DNA repair data. The most relevant ones, all related to DNA repair, were employed to build a predictor. Predictors constructed with random forest and minimum bounding sphere predicted late Grade ≥ 3 AEs with a sensitivity of 100% and specificity of 77.17 and 86.22%, respectively. This multiplex functional approach strongly supports a dominant role for DSB repair in the development of chronic AEs. It also showed that affected patients share specific features related to functional aspects of DSB repair. This strategy may be suitable for routine clinical analysis and paves the way for modelling DSB repair associated with severe AEs induced by radiotherapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Social prescribing is a non-clinical approach to addressing social, environmental, and economic factors affecting how people feel physical and/or emotionally. It involves connecting people to "community assets" (e.g., local groups, organizations, and charities) that can contribute to positive well-being. We sought to explain in what ways, for whom, and why the cultural sector can support social prescribing with older people. We conducted semi-structured interviews with 28 older people (aged 60+) and 25 cultural sector staff. The following nine concepts, developed from interview data, progressed the understanding of tailoring cultural offers, which came from our previous realist review- immersion, buddying, café culture, capacity, emotional involvement, perseverance, autonomy, elitism, and virtual cultural offers. Through tailoring, we propose that older people might experience one or more of the following benefits from engaging with a cultural offer as part of social prescribing-being immersed, psychological holding, connecting, and transforming through self-growth.

The sudden and dramatic advent of the COVID-19 pandemic led to urgent demands for timely, relevant, yet rigorous research. This paper discusses the origin, design, and execution of the SolPan research commons, a large-scale, international, comparative, qualitative research project that sought to respond to the need for knowledge among researchers and policymakers in times of crisis. The form of organization as a research commons is characterized by an underlying solidaristic attitude of its members and its intrinsic organizational features in which research data and knowledge in the study is shared and jointly owned. As such, the project is peer-governed, rooted in (idealist) social values of academia, and aims at providing tools and benefits for its members. In this paper, we discuss challenges and solutions for qualitative studies that seek to operate as research commons., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

The repair of DNA double-strand breaks (DSBs) involves interdependent molecular pathways, of which the choice is crucial for a cell's fate when facing a damage. Growing evidence points toward the fact that DSB repair capacities correlate with disease aggressiveness, treatment response and treatment-related toxicities in cancer. Scientific and medical communities need more easy-to-use and efficient tools to rapidly estimate DSB repair capacities from a tissue, enable routine-accessible treatment personalization, and hopefully, improve survival. Here, we propose a new functional biochip assay (NEXT-SPOT) that characterizes DSB repair-engaged cellular pathways and provides qualitative and quantitative information on the contribution of several pathways in less than 2 h, from 10 mg of cell lysates. We introduce the NEXT-SPOT technology, detail the molecular characterizations of different repair steps occurring on the biochip, and show examples of DSB repair profiling using three cancer cell lines treated or not with a DSB-inducer (doxorubicin) and/or a DNA repair inhibitor (RAD51 inhibitor; DNA-PK inhibitor; PARP inhibitor). Among others, we demonstrate that NEXT-SPOT can accurately detect decreased activities in strand invasion and end-joining mechanisms following DNA-PK or RAD51 inhibition in DNA-PK-proficient cell lines. This approach offers an all-in-one reliable strategy to consider DSB repair capacities as predictive biomarkers easily translatable to the clinic., (© 2022. The Author(s).)

Older people's well-being can be bolstered by engaging with cultural activities and venues. They may be encouraged to try cultural offers by a link worker as part of social prescribing. However, the cultural sector, like all parts of life, was affected by the COVID-19 pandemic; this has had implications for cultural offers available to link workers. A study was conducted to explore the views and experiences of link workers in using the cultural sector within social prescribing, particularly for older people (aged 60+) during the pandemic. An online questionnaire was distributed to and completed by link workers in the UK. Data were analysed mainly using descriptive statistics. Open text responses were clustered into similar ideas to create key concepts. Useable responses were received from 148 link workers. They highlighted a general lack of interaction between link workers and the cultural sector about how the latter could support social prescribing. Results suggested that personal familiarity with cultural offers might prompt link workers to refer to them. Some respondents proposed that cultural offers were regarded as elitist, which deterred them from referring there. However, there was a general acknowledgement that the cultural sector could contribute to social prescribing. Link workers need to regard the cultural sector as accessible, appropriate, adequate, affordable and available before referring older people to cultural offers as part of social prescribing. Link workers may benefit from becoming more familiar with cultural sector staff and offers, including online resources, so they can then propose them to patients with confidence., (© 2022 The Authors. Health and Social Care in the Community published by John Wiley & Sons Ltd.)

Background: Non-medical issues (e.g. loneliness, financial concerns, housing problems) can shape how people feel physically and psychologically. This has been emphasised during the Covid-19 pandemic, especially for older people. Social prescribing is proposed as a means of addressing non-medical issues, which can include drawing on support offered by the cultural sector., Method: A rapid realist review was conducted to explore how the cultural sector (in particular public/curated gardens, libraries and museums), as part of social prescribing, can support the holistic well-being of older people under conditions imposed by the pandemic. An initial programme theory was developed from our existing knowledge and discussions with cultural sector staff. It informed searches on databases and within the grey literature for relevant documents, which were screened against the review's inclusion criteria. Data were extracted from these documents to develop context-mechanism-outcome configurations (CMOCs). We used the CMOCs to refine our initial programme theory., Results: Data were extracted from 42 documents. CMOCs developed from these documents highlighted the importance of tailoring-shaping support available through the cultural sector to the needs and expectations of older people-through messaging, matching, monitoring and partnerships. Tailoring can help to secure benefits that older people may derive from engaging with a cultural offer-being distracted (absorbed in an activity) or psychologically held, making connections or transforming through self-growth. We explored the idea of tailoring in more detail by considering it in relation to Social Exchange Theory., Conclusions: Tailoring cultural offers to the variety of conditions and circumstances encountered in later life, and to changes in social circumstances (e.g. a global pandemic), is central to social prescribing for older people involving the cultural sector. Adaptations should be directed towards achieving key benefits for older people who have reported feeling lonely, anxious and unwell during the pandemic and recovery from it., (© 2022. The Author(s).)

To see if variations in timing of rapamycin (Rapa), administered to middle aged mice starting at 20 months, would lead to different survival outcomes, we compared three dosing regimens. Initiation of Rapa at 42 ppm increased survival significantly in both male and female mice. Exposure to Rapa for a 3-month period led to significant longevity benefit in males only. Protocols in which each month of Rapa treatment was followed by a month without Rapa exposure were also effective in both sexes, though this approach was less effective than continuous exposure in female mice. Interpretation of these results is made more complicated by unanticipated variation in patterns of weight gain, prior to the initiation of the Rapa treatment, presumably due to the use of drug-free food from two different suppliers. The experimental design included tests of four other drugs, minocycline, β-guanidinopropionic acid, MitoQ, and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), but none of these led to a change in survival in either sex., (© 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Food consumption is fundamental for life, and eating disorders often result in devastating or life-threatening conditions. Anorexia nervosa (AN) is characterized by a persistent restriction of energy intake, leading to lowered body weight, constant fear of gaining weight, and psychological disturbances of body perception. Herein, we demonstrate that SIRT1 inhibition, both genetically and pharmacologically, delays the onset and progression of AN behaviors in activity-based anorexia (ABA) models, while SIRT1 activation accelerates ABA phenotypes. Mechanistically, we suggest that SIRT1 promotes progression of ABA, in part through its interaction with NRF1, leading to suppression of a NMDA receptor subunit Grin2A. Our results suggest that AN may arise from pathological positive feedback loops: voluntary food restriction activates SIRT1, promoting anxiety, hyperactivity, and addiction to starvation, exacerbating the dieting and exercising, thus further activating SIRT1. We propose SIRT1 inhibition can break this cycle and provide a potential therapy for individuals suffering from AN.

The first domesticated companion animal, the dog, is currently represented by over 190 unique breeds. Across these numerous breeds, dogs have exceptional variation in lifespan (inversely correlated with body size), presenting an opportunity to discover longevity-determining traits. We performed a genome-wide association study on 4169 canines representing 110 breeds and identified novel candidate regulators of longevity. Interestingly, known functions within the identified genes included control of coat phenotypes such as hair length, as well as mitochondrial properties, suggesting that thermoregulation and mitochondrial bioenergetics play a role in lifespan variation. Using primary dermal fibroblasts, we investigated mitochondrial properties of short-lived (large) and long-lived (small) dog breeds. We found that cells from long-lived breeds have more uncoupled mitochondria, less electron escape, greater respiration, and capacity for respiration. Moreover, our data suggest that long-lived breeds have higher rates of catabolism and β-oxidation, likely to meet elevated respiration and electron demand of their uncoupled mitochondria. Conversely, cells of short-lived (large) breeds may accumulate amino acids and fatty acid derivatives, which are likely used for biosynthesis and growth. We hypothesize that the uncoupled metabolic profile of long-lived breeds likely stems from their smaller size, reduced volume-to-surface area ratio, and therefore a greater need for thermogenesis. The uncoupled energetics of long-lived breeds lowers reactive oxygen species levels, promotes cellular stress tolerance, and may even prevent stiffening of the actin cytoskeleton. We propose that these cellular characteristics delay tissue dysfunction, disease, and death in long-lived dog breeds, contributing to canine aging diversity.

Parkinson's disease is characterized by progressive death of dopaminergic neurons, leading to motor and cognitive dysfunction. Epidemiological studies consistently show that the use of tobacco reduces the risk of Parkinson's. We report that nicotine reduces the abundance of SIRT6 in neuronal culture and brain tissue. We find that reduction of SIRT6 is partly responsible for neuroprotection afforded by nicotine. Additionally, SIRT6 abundance is greater in Parkinson's patient brains, and decreased in the brains of tobacco users. We also identify SNPs that promote SIRT6 expression and simultaneously associate with an increased risk of Parkinson's. Furthermore, brain-specific SIRT6 knockout mice are protected from MPTP-induced Parkinson's, while SIRT6 overexpressing mice develop more severe pathology. Our data suggest that SIRT6 plays a pathogenic and pro-inflammatory role in Parkinson's and that nicotine can provide neuroprotection by accelerating its degradation. Inhibition of SIRT6 may be a promising strategy to ameliorate Parkinson's and neurodegeneration.

Apoptosis is essential for numerous processes, such as development, resistance to infections, and suppression of tumorigenesis. Here, we investigate the influence of the nutrient sensing and longevity-assuring enzyme SIRT6 on the dynamics of apoptosis triggered by serum starvation. Specifically, we characterize the progression of apoptosis in wild type and SIRT6 deficient mouse embryonic fibroblasts using time-lapse flow cytometry and computational modelling based on rate-equations and cell distribution analysis. We find that SIRT6 deficient cells resist apoptosis by delaying its initiation. Interestingly, once apoptosis is initiated, the rate of its progression is higher in SIRT6 null cells compared to identically cultured wild type cells. However, SIRT6 null cells succumb to apoptosis more slowly, not only in response to nutrient deprivation but also in response to other stresses. Our data suggest that SIRT6 plays a role in several distinct steps of apoptosis. Overall, we demonstrate the utility of our computational model to describe stages of apoptosis progression and the integrity of the cellular membrane. Such measurements will be useful in a broad range of biological applications.