New Directions in Geroscience: Integrating Social and Behavioral Drivers of Biological Aging.

ABSTRACT: The "geroscience hypothesis" posits that slowing the physiological processes of aging would lead to delayed disease onset and longer healthspan and lifespan. This shift from a focus on solely treating existing disease to slowing the aging process is a shift toward prevention, including a focus on risk factors found in the social environment. Although geroscience traditionally has focused on the molecular and cellular drivers of biological aging, more fundamental causes of aging may be found in the social exposome-the complex array of human social environmental exposures that shape health and disease. The social exposome may interact with physiological processes to accelerate aging biology. In this commentary, we review the potential of these insights to shape the emerging field of translational geroscience. The articles in this special issue highlight how social stress and social determinants of health are associated with biomarkers of aging such as inflammation, epigenetic clocks, and telomeres, and spotlight promising interventions to mitigate stress-related inflammation. For geroscience to incorporate the social exposome into its translational agenda, studies are needed that elucidate and quantify the effects of social exposures on aging and that consider social exposures as intervention targets. The life course perspective allows us to measure both exposures and aging biology over time including sensitive periods of development and major social transitions. In addition, given rapid changes in the measurement of aging biology, which include machine learning techniques, multisystem phenotypes of aging are being developed to better reflect whole body aging, replacing reliance on single system biomarkers. In this expanded and more integrated field of translational geroscience, strategies targeting factors in the social exposome hold promise for achieving aging health equity and extending healthy longevity.

Celebrating 20 years of longitudinal research on aging in Mexico.

The Division of Behavioral and Social Research (BSR) at the National Institute on Aging (NIA), National Institutes of Health (NIH), is the leading U.S. funder of social, behavioral, psychological, and economic research on the processes of aging at the individual and population level. A cornerstone of our investments is the Health and Retirement Study (HRS), a longitudinal study launched by NIA in 1992 with support from the Social Security Administration.

The importance of identifying underlying process abnormalities in alexithymia: Implications of the three-process model and a single case study illustration.

We present an in-depth case study of a rare individual (whom we will refer to as "Jane") who reported an inability to experience emotion. Jane completed a range of assessments measuring alexithymia, emotional awareness, and emotion recognition ability. She, along with 22 control participants, also underwent skin conductance (SC) measurement and facial electromyography (EMG) during exposure to affective images, and self reported the valence/arousal of their responses to those images. Jane scored high on alexithymia and low on emotional awareness; yet she performed well on emotion recognition measures and showed a typical pattern of valence ratings. Her SC responses and subjective arousal ratings were atypically low, and some of her EMG responses were also atypical. Jane's deficit profile highlights the dissociability of self-focused emotional awareness and other-focused emotion recognition ability, as well as the dissociability between the generation and representation of valence and arousal (with both subjective and objective measures).

A joint venture: patients' experiences with goal setting in rheumatology rehabilitation - a qualitative study.

PURPOSE: To explore how patients with rheumatic musculoskeletal diseases (RMDs) perceive participation in the goal setting process prior to interdisciplinary rehabilitation. METHODS: We conducted semi-structured interviews with 22 participants admitted to an interdisciplinary rehabilitation stay for patients with RMDs at two Danish rehabilitation centres. Qualitative content analysis was applied. RESULTS: The participants perceived goal setting as a joint venture between two parties: the health professionals and the participant. Three categories were formed, which described both facilitators and barriers in the process. Responsibility for goal setting described the importance of shared responsibility, or health professionals as experts, taking full responsibility for goal setting. Equipped for goal setting included perceptions of being well prepared for the process, or considerations that goal setting was difficult because of a lack of information. An equal member of the team entailed both the feeling of being recognised as one in the team, or feeling like an outsider. CONCLUSION: Goal setting is perceived as a challenge by some patients. Participation in goal setting depends on both the capacity and the opportunity to participate which are factors linked to patients' level of health literacy.

Patients largely perceive goal setting as a joint venture, constituting a partnership aimed at sharing decisions regarding one or more rehabilitation goals, yet, for some patients, active participation in this joint venture poses challenges.When patients perceive a shared responsibility, acquire appropriate and sufficient knowledge prior to the process and feel accepted as whole persons based on a biopsychosocial approach it facilitates goal setting.Health professionals should be aware of barriers perceived by patients, such as abdicating responsibility because they view health professionals as authority figures, feeling uncertain about the purpose of setting goals and having difficulties in receiving and applying information.Patients' health literacy as well health literacy responsiveness may be of importance to the experience of barriers to shared decisions and goal setting among patients with RMDs.

National Institute on Aging's 50th anniversary: Advancing aging research and the health and well-being of older adults.

The National Institute on Aging (NIA), part of the National Institutes of Health (NIH), was founded in 1974 to support and conduct research on aging and the health and well-being of older adults. Fifty years ago, the concept of studying aging generated much skepticism. Early NIA-funded research findings helped establish the great value of aging research and provided the foundation for significant science advances that have improved our understanding of the aging process, diseases and conditions associated with aging, and the effects of health inequities, as well as the need to promote healthy aging lifestyles. Today, we celebrate the many important contributions to aging research made possible by NIA, as well as opportunities to continue to make meaningful progress. NIA emphasizes that the broad aging research community must continue to increase and expand our collective efforts to recruit and train a diverse next generation of aging researchers.

On the influence of water on the electronic structure of firefly oxyluciferin anions from absorption spectroscopy of bare and monohydrated ions in vacuo.

A complete understanding of the physics underlying the varied colors of firefly bioluminescence remains elusive because it is difficult to disentangle different enzyme-lumophore interactions. Experiments on isolated ions are useful to establish a proper reference when there are no microenvironmental perturbations. Here, we use action spectroscopy to compare the absorption by the firefly oxyluciferin lumophore isolated in vacuo and complexed with a single water molecule. While the process relevant to bioluminescence within the luciferase cavity is light emission, the absorption data presented here provide a unique insight into how the electronic states of oxyluciferin are altered by microenvironmental perturbations. For the bare ion we observe broad absorption with a maximum at 548 ± 10 nm, and addition of a water molecule is found to blue-shift the absorption by approximately 50 nm (0.23 eV). Test calculations at various levels of theory uniformly predict a blue-shift in absorption caused by a single water molecule, but are only qualitatively in agreement with experiment highlighting limitations in what can be expected from methods commonly used in studies on oxyluciferin. Combined molecular dynamics simulations and time-dependent density functional theory calculations closely reproduce the broad experimental peaks and also indicate that the preferred binding site for the water molecule is the phenolate oxygen of the anion. Predicting the effects of microenvironmental interactions on the electronic structure of the oxyluciferin anion with high accuracy is a nontrivial task for theory, and our experimental results therefore serve as important benchmarks for future calculations.

Electronic coupling between photo-excited stacked bases in DNA and RNA strands with emphasis on the bright states initially populated.

In biology the interplay between multiple light-absorbers gives rise to complex quantum effects such as superposition states that are of extreme importance for life, both for harvesting solar energy and likely protecting nucleic acids from radiation damage. Still the characteristics of these states and their quantum dynamics are a much debated issue. While the electronic properties of single bases are fairly well understood, the situation for strands is complicated by the fact that stacked bases electronically couple when photoexcited. These newly arising states are denoted as exciton states and are simply linear combinations of localised wavefunctions that involve N - 1 ground-state bases and one base in its excited state (cf. the Frenkel exciton model). There is disagreement over the number of bases, N, that coherently couple, i.e., the spatial extent of the exciton, and how electronic deexcitation back to the ground state occurs. The importance of dark charge-transfer states has been inferred both from time-resolved fluorescence and transient absorption experiments. These states were suggested to be responsible for long deexcitation times but it is unclear whether 'long' is tens of picoseconds or nanoseconds. In this review paper, we focus on the bright states initially populated and discuss their nature based on information obtained from systematic absorption and circular dichroism experiments on single strands of different lengths. Our results from the last five years are compared with those from other groups, and are discussed in the context of successive deexcitation schemes. Pieces to the puzzle have come from different experiments and theory but a complete description has yet to emerge. As such the story about DNA/RNA photophysical decay mechanisms resembles the tale about the blind men and the elephant where all see the beast in different, correct but incomplete ways.

Estimating the impact of low temperature on African swine fever virus transmission through contaminated environments.

African Swine Fever Virus (ASFV) is the cause of an infectious disease in pigs, which is difficult to control. Long viability of ASFV has been shown for several contaminated materials, especially under low temperature. Therefore, when pigs are exposed to a contaminated environment, new infections could occur without the presence of infectious individuals. For example, a contaminated, poorly washed, empty livestock vehicle poses a risk to the next load of pigs. A quantitative stochastic environmental transmission model was applied to simulate the change in environmental contamination levels over time and calculate the epidemic parameters through exposure-based estimation. Due to the lack of experimental data on environmental transmission at low temperatures, we performed a non-linear fit of the decay rate parameter with temperature based on a literature review. Eventually, 16 scenarios were constructed for different temperature (at 20 °C, 10 °C, 0 °C, or -10 °C) and duration of empty periods (1, 3, 5, or 7 days) after the environment had been contaminated. We quantified the variation in the contamination level of the environment over time and the probability of newly added recipients getting infected when exposed to the environment after the empty period. As a result, the transmission rate parameter for ASFV in pigs was estimated to be 1.53 (0.90, 2.45) day-1, the decay rate parameter to be 1.02 (0.73, 1.47) day-1 (at 21 °C), and the excretion rate parameter to be 2.70 (2.51, 3.02) day-1. Without washing and disinfecting, the environment required 9, 14, 24, 54 days to reach a low probability of causing at least one new case (<0.005) at 20 °C, 10 °C, 0 °C, -10 °C, respectively. In addition, the method proposed in this paper enables assessment of the effect of washing and disinfecting on ASFV environmental transmission. We conducted this study to better understand how the viability of ASFV at different temperatures could affect the infectivity in environmental transmission and to improve risk assessment and disease control strategies.

Why Definitional Clarity Matters: Implications for the Operationalization of Emotional Well-Being.

The National Institutes of Health (NIH) is increasingly prioritizing research on health-promoting processes. Park et al. (this issue) respond to a call made by NIH to advance the study of emotional well-being (EWB) and to increase understanding of the fundamental constituents of EWB across the lifespan and among diverse subgroups. They propose a definition of EWB that provides an organizing framework for research on 'psychological aspects of well-being' and health. We commend this important first step and urge consideration of three important issues related to operationalization - the process by which an abstract concept is transformed into variables that can be measured - in future research on EWB. We expect that an iterative process of construct refinement and empirical validation will advance the study of EWB, producing scientific discoveries that can be leveraged to enhance health across the lifespan.

The NIH Science of Behavior Change Program: Looking Toward the Future.

The National Institutes of Health established the Science of Behavior Change (SOBC) program to promote basic research on the initiation, personalization, and maintenance of health behavior change. The SOBC Resource and Coordinating Center now leads and supports activities to maximize the creativity, productivity, scientific rigor, and dissemination of the experimental medicine approach and experimental design resources. Here, we highlight those resources, including the Checklist for Investigating Mechanisms in Behavior-change Research (CLIMBR) guidelines introduced in this special section. We describe the ways in which SOBC can be applied across a range of domains and contexts, and end by considering ways to extend SOBC's perspective and reach, so as to best promote behavior change linked with health, quality of life, and well-being.

Vacuum-ultraviolet circular dichroism reveals DNA duplex formation between short strands of adenine and thymine.

Absorbance spectroscopy is used extensively to tell when two DNA single strands come together and form a double strand. Here we show that circular dichroism in the vacuum ultraviolet region provides an even stronger indication for duplex formation in the case of short strands of adenine and thymine (4 to 16 bases in each strand). Indeed, our results show that a strong positive CD band appears at 179 nm when double strands are formed. Melting experiments were done in aqueous solution with and without added Na(+) counter ions. With additional salt present a huge increase in the 179 nm CD band was observed when lowering the temperature. A 179 nm CD marker band for duplex formation can be used to measure the kinetics for the association of two single strands. Such experiments rely on large changes at one particular wavelength since it is too time-consuming to record a full-wavelength spectrum.

Absorption by DNA single strands of adenine isolated in vacuo: the role of multiple chromophores.

The degree of electronic coupling between DNA bases is a topic being up for much debate. Here we report on the intrinsic electronic properties of isolated DNA strands in vacuo free of solvent, which is a good starting point for high-level excited states calculations. Action spectra of DNA single strands of adenine reveal sign of exciton coupling between stacked bases from blueshifted absorption bands (~3 nm) relative to that of the dAMP mononucleotide (one adenine base). The bands are blueshifted by about 10 nm compared to those of solvated strands, which is a shift similar to that for the adenine molecule and the dAMP mononucleotide. Desolvation has little effect on the bandwidth, which implies that inhomogenous broadening of the absorption bands in aqueous solution is of minor importance compared to, e.g., conformational disorder. Finally, at high photon energies, internal conversion competes with electron detachment since dissociation of the bare photoexcited ions on the microsecond time scale is measured.

SWOT analysis of risk factors associated with introduction of African Swine Fever through vehicles returning after export of pigs.

Denmark is a major pig exporter and applies a high level of biosecurity, with washing and disinfecting stations for returning livestock vehicles. The introduction of African Swine Fever (ASF) would have significant economic consequences related to loss of export of live pigs and products thereof. In this study, we focused on the role of empty livestock vehicles returning after exports of pigs for the introduction of ASF. Initially, the current components and measures related to export of livestock were described. Next, analyses of strengths, weaknesses, opportunities, and threats (SWOT) were conducted, covering the components and measures identified. Then, export of pigs was described either through assembly centers or directly from farms. Washing and disinfection, as required and undertaken at the designated stations, constitutes the most important among all risk-reducing measures identified. Recommendations are to: (1) ensure the quality of washing and disinfection through staff training; (2) find new, safe, and more efficient disinfectants; (3) ensure the required temperature, and therefore effect, of the disinfectant and water. It was impossible to assess, the influence of export through assembly centers compared to direct transport. However, through SWOT analyses we identified the strengths and weaknesses of the two pathways. Moreover, components/measures with risks of unknown sizes are also discussed, such as vehicles undertaking cabotage and the current vehicle quarantine periods.

Submerged aquatic vegetation: Overview of monitoring techniques used for the identification and determination of spatial distribution in European coastal waters.

Coastal waters are highly productive and diverse ecosystems, often dominated by marine submerged aquatic vegetation (SAV) and strongly affected by a range of human pressures. Due to their important ecosystem functions, for decades, both researchers and managers have investigated changes in SAV abundance and growth dynamics to understand linkages to human perturbations. In European coastal waters, monitoring of marine SAV communities traditionally combines diver observations and/or video recordings to determine, for example, spatial coverage and species composition. While these techniques provide very useful data, they are rather time consuming, labor-intensive, and limited in their spatial coverage. In this study, we compare traditional and emerging remote sensing technologies used to monitor marine SAV, which include satellite and occupied aircraft operations, aerial drones, and acoustics. We introduce these techniques and identify their main strengths and limitations. Finally, we provide recommendations for researchers and managers to choose the appropriate techniques for future surveys and monitoring programs. Integr Environ Assess Manag 2022;18:892-908. © 2021 SETAC.

Novel approach to large-scale monitoring of submerged aquatic vegetation: A nationwide example from Sweden.

According to the EU Habitats directive, the Water Framework Directive, and the Marine Strategy Framework Directive, member states are required to map, monitor, and evaluate changes in quality and areal distribution of different marine habitats and biotopes to protect the marine environment more effectively. Submerged aquatic vegetation (SAV) is a key indicator of the ecological status of coastal ecosystems and is therefore widely used in reporting related to these directives. Environmental monitoring of the areal distribution of SAV is lacking in Sweden due to the challenges of large-scale monitoring using traditional small-scale methods. To address this gap, in 2020, we embarked on a project to combine Copernicus Sentinel-2 satellite imagery, novel machine learning (ML) techniques, and advanced data processing in a cloud-based web application that enables users to create up-to-date SAV classifications. At the same time, the approach was used to derive the first high-resolution SAV map for the entire coastline of Sweden, where an area of 1550 km2 was mapped as SAV. Quantitative evaluation of the accuracy of the classification using independent field data from three different regions along the Swedish coast demonstrated relative high accuracy within shallower areas, particularly where water transparency was high (average total accuracy per region 0.60-0.77). However, the classification missed large proportions of vegetation growing in deeper water (on average 31%-50%) and performed poorly in areas with fragmented or mixed vegetation and poor water quality, challenges that should be addressed in the development of the mapping methods towards integration into monitoring frameworks such as the EU directives. In this article, we present the results of the first satellite-derived SAV classification for the entire Swedish coast and show the implementation of a cloud-based SAV mapping application (prototype) developed within the frame of the project. Integr Environ Assess Manag 2022;18:909-920. © 2021 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Anticipation of monetary gain but not loss in healthy older adults.

Although global declines in structure have been documented in the aging human brain, little is known about the functional integrity of the striatum and prefrontal cortex in older adults during incentive processing. We used event-related functional magnetic resonance imaging to determine whether younger and older adults differed in both self-reported and neural responsiveness to anticipated monetary gains and losses. The present study provides evidence for intact striatal and insular activation during gain anticipation with age, but shows a relative reduction in activation during loss anticipation. These findings suggest that there is an asymmetry in the processing of gains and losses in older adults that may have implications for decision-making.

The Emerging Science of Interoception: Sensing, Integrating, Interpreting, and Regulating Signals within the Self.

Interoception refers to the representation of the internal states of an organism, and includes the processes by which it senses, interprets, integrates, and regulates signals from within itself. This review presents a unified research framework and attempts to offer definitions for key terms to describe the processes involved in interoception. We elaborate on these definitions through illustrative research findings, and provide brief overviews of central aspects of interoception, including the anatomy and function of neural and non-neural pathways, diseases and disorders, manipulations and interventions, and predictive modeling. We conclude with discussions about major research gaps and challenges.

Vacuum-ultraviolet circular dichroism spectroscopy of DNA: a valuable tool to elucidate topology and electronic coupling in DNA.

Circular dichroism (CD) is a powerful technique to obtain information on electronic transitions and has been used extensively for studies on DNA. Most experiments are done in the UV region but new information is often revealed from extending the wavelength region down into the vacuum ultraviolet (VUV) region. Such experiments are most easily carried out with synchrotron radiation (SR) light sources that provide large photon fluxes. Here we provide a summary of the SRCD data taken on different DNA strands with emphasis on results from our own laboratory within the last five years.(1-3) Signal intensities in the VUV are often significantly larger than those in the UV, and the electronic coupling between bases may increase with excitation energy. CD spectroscopy is particularly useful for investigating the extent of electronic coupling within a strand, i.e., the degree of delocalisation of the excited-state electronic wavefunction. The spatial extent of the wavefunction may be limited to just one base or it extends over two or more bases in a stack or between bases on different strands.(4,5) The actual character of the electronically excited state is linked to base composition and sequence as well as DNA folding motif (A-, B-, Z-DNA, triplexes, quadruplexes, etc.). The latter depends on experimental conditions such as solution acidity, temperature, ionic strength, and solvent.

Electronic coupling between cytosine bases in DNA single strands and i-motifs revealed from synchrotron radiation circular dichroism experiments.

In this work we have recorded synchrotron radiation circular dichroism (SRCD) spectra from 180 nm to 360 nm of cytosine strands [(dC)(n), n = 1, 2, ..., 10] in aqueous solution at different pH values to reveal electronic coupling between bases in different ionisation states. The geometry of the strands is determined by the pH value and the strand length and the local organisation of the cytosines will determine the base-to-base interaction that impacts on the CD signal. At low pH where all bases are protonated, there is no signature of electronic coupling between the bases, and the SRCD spectrum is simply n times that of the n = 1 spectrum. At higher pH where all bases are neutral, the spectra for n > 1 differ from the monomer spectrum, which implies electronic coupling between bases. The correlation between the CD signal and n is linear, and the spatial extent of the excited state wavefunction is therefore over just two stacked bases both in the UV and VUV. At intermediate pH, the low-n spectra are different from the high-n spectra, and a transition is seen to occur at n = 6-8. We ascribe this behavior to the formation of i-motif structures between four (dC)(n) strands for high n.

Fingerprints of bonding motifs in DNA duplexes of adenine and thymine revealed from circular dichroism: synchrotron radiation experiments and TDDFT calculations.

Synchrotron radiation circular dichroism (SRCD) spectra were recorded for a family of 12 DNA duplexes that all contain nine adenines (A) and nine thymines (T) in each strand but in different combinations. The total number of AT Watson-Crick (WC) base pairs is constant (18), but the number of cross-strand (CS) hydrogen bonds between A and T varies between 0 and 16, the maximum possible. Eleven of the duplexes have one or more A tracts, and one duplex has T tracts. The signals due to hybridization were found from subtraction of spectra of single strands from spectra of the duplexes. The residual spectrum of the T-tract duplex T(9)A(9):A(9)T(9) (5'-3':3'-5') significantly differs from that of the A-tract duplex A(9)T(9):T(9)A(9), but only below 210 nm, which suggests that the signal in this region depends on the superhelicity of the duplex. A principal component analysis of all residual spectra reveals that spectra of A-tract duplexes can be obtained to a good approximation as a linear combination of just two basis spectra. The first component is assigned to the spectrum of 18 WC and 8 CS pairs, whereas the second component is that of 8 CS pairs. This interpretation is supported by separate experiments on duplexes of varying lengths but with similar arrangements of the A and T's and by experiments on two other duplex families of 14 and 30 base pairs. The best correlation is obtained by the assumption that cross-strand interactions occur as long as there are two adenine neighbors in a strand. Our data indicate that a circular dichroism spectrum of a duplex containing only A and T can simply be inferred from the number of WC base pairs and the number of CS interactions, and we provide reference spectra for these two interactions. Finally, time dependent density functional theory calculations of the circular dichroism spectra for an isolated WC base pair and two different CS base pairs (between adenine N-6 amine and thymine O-4 or between adenine C-2-H and thymine O-2) were performed to provide some additional support for the interpretation of the experimental spectra. We find large differences between the two calculated CS spectra. However, there is a reasonable qualitative agreement between the calculated WC and the C-2-H...O-2 CS spectra and those deduced from the experimental data.