Task-specific resistance training adaptations in older adults: comparing traditional and functional exercise interventions.

Muscle strength declines ∼3% per year after the age of 70. Resistance training guidelines for older adults are often based on free-weight and machine exercises, which may be inaccessible and lack carryover to activities of daily living. We tested the hypothesis that resistance training adaptations in older adults are task-specific. Thirty adults (8 males, 22 females; mean age = 71 years) were randomly assigned to participate in 6 weeks of supervised, high-intensity resistance training (twice per week) utilizing free-weight and machine exercises (traditional) versus functional activities that were overloaded with a weighted vest (functional). Participants were thoroughly familiarized with the exercises and testing prior to beginning the study. Major outcome measures included assessments of functional performance, five-repetition maximum strength, isometric knee extensor force, and quadriceps muscle size. Physical activity and nutrition were monitored. The study results demonstrate that the magnitude of improvement within a given outcome was largely dependent on group assignment, with greater improvements in gait speed and the timed-up-and-go in the functional group, but 2-3× greater five repetition maximum strength improvements for the trap bar deadlift, leg press, and leg extension following traditional resistance training. Both groups showed improvements in isometric knee extensor force and muscle size, suggesting that some aspects of the observed adaptations were generic, rather than specific. Overall, these novel findings suggest that, among older adults, 1) resistance training adaptations exhibit a high degree of task specificity and 2) significant improvements in functional outcomes can be achieved with the use of a weighted vest.

Combined action observation and mental imagery versus neuromuscular electrical stimulation as novel therapeutics during short-term knee immobilization.

Limb immobilization causes rapid declines in muscle strength and mass. Given the role of the nervous system in immobilization-induced weakness, targeted interventions may be able to preserve muscle strength, but not mass, and vice versa. The purpose of this study was to assess the effects of two distinct interventions during 1 week of knee joint immobilization on muscle strength (isometric and concentric isokinetic peak torque), mass (bioimpedance spectroscopy and ultrasonography), and neuromuscular function (transcranial magnetic stimulation and interpolated twitch technique). Thirty-nine healthy, college-aged adults (21 males, 18 females) were randomized into one of four groups: immobilization only (n = 9), immobilization + action observation/mental imagery (AOMI) (n = 10), immobilization + neuromuscular electrical stimulation (NMES) (n = 12), or control group (n = 8). The AOMI group performed daily video observation and mental imagery of knee extensions. The NMES group performed twice daily stimulation of the quadriceps femoris. Based on observed effect sizes, it appears that AOMI shows promise as a means of preserving voluntary strength, which may be modulated by neural adaptations. Strength increased from PRE to POST in the AOMI group, with +7.2% (Cohen's d = 1.018) increase in concentric isokinetic peak torque at 30°/s. However, NMES did not preserve muscle mass. Though preliminary, our findings highlight the specific nature of clinical interventions and suggest that muscle strength can be independently targeted during rehabilitation. This study was prospectively registered: ClinicalTrials.gov NCT05072652.

fNIRS is capable of distinguishing laterality of lower body contractions.

The use of functional near-infrared spectroscopy (fNIRS) for brain imaging during human movement continues to increase. This technology measures brain activity non-invasively using near-infrared light, is highly portable, and robust to motion artifact. However, the spatial resolution of fNIRS is lower than that of other imaging modalities. It is unclear whether fNIRS has sufficient spatial resolution to differentiate nearby areas of the cortex, such as the leg areas of the motor cortex. Therefore, the purpose of this study was to determine fNIRS' ability to discern laterality of lower body contractions. Activity in the primary motor cortex was recorded in forty participants (mean = 23.4 years, SD = 4.5, female = 23, male = 17) while performing unilateral lower body contractions. Contractions were performed at 30% of maximal force against a handheld dynamometer. These contractions included knee extension, knee flexion, dorsiflexion, and plantar flexion of the left and right legs. fNIRS signals were recorded and stored for offline processing and analysis. Channels of fNIRS data were grouped into regions of interest, with five tolerance conditions ranging from strict to lenient. Four of five tolerance conditions resulted in significant differences in cortical activation between hemispheres. During right leg contractions, the left hemisphere was more active than the right hemisphere. Similarly, during left leg contractions, the right hemisphere was more active than the left hemisphere. These results suggest that fNIRS has sufficient spatial resolution to distinguish laterality of lower body contractions. This makes fNIRS an attractive technology in research and clinical applications in which laterality of brain activity is required during lower body activity.

Sex differences in muscle-quality recovery following one week of knee joint immobilization and subsequent retraining.

This manuscript represents the second phase of a clinical trial designed to examine the effects of knee joint immobilization and retraining on muscle strength and mass. In Phase 2, we examined sex differences in the recovery of multiple indices of muscle quality after a resistance training-based rehabilitation program. Following 1 week of immobilization, 27 participants (16 males, 11 females) exhibiting weakness underwent twice weekly resistance training sessions designed to re-strengthen their left knee. Unilateral retraining sessions utilizing leg press, extension, and curl exercises were conducted until participants could reproduce their pre-immobilization knee extension isometric maximal voluntary contraction (MVC) peak torque. Post-immobilization, both sexes demonstrated impaired MVC peak torque (males = -10.8%, females = -15.2%), specific torque (-9.8% vs. -13.1%), echo intensity of the vastus lateralis (+6.9% vs. +5.9%) and rectus femoris (+5.9% vs. +2.1), and extracellular water/intracellular water ratio (+7.8% vs. +9.0%). The number of retraining sessions for peak torque to return to baseline for males (median = 1, mean = 2.13) versus females (median = 2, mean = 2.91) was not significantly different, though the disparity in recovery times may be clinically relevant. Following retraining, specific torque was the only muscle-quality indicator that improved along with MVC peak torque (males = 20.1%, females = 22.4%). Our findings indicate that measures of muscle quality demonstrate divergent recovery rates following immobilization, with muscle mass lagging behind improvements in strength. Greater immobilization-induced strength loss among females suggests that sex-specific rehabilitation efforts may be justified.

A comparison of techniques for verifying the accuracy of precision decomposition-derived relationships between motor unit firing rates and recruitment thresholds from surface EMG signals.

Approaches for validating motor unit firing times following surface electromyographic (EMG) signal decomposition with the precision decomposition III (PDIII) algorithm have not been agreed upon. Two approaches have been common: (1) "reconstruct-and-test" and (2) spike-triggered averaging (STA). We sought to compare motor unit results following the application of these approaches. Surface EMG signals were recorded from the vastus lateralis of 13 young males performing trapezoidal, isometric knee extensions at 50% and 80% of maximum voluntary contraction (MVC) force. The PDIII algorithm was used to quantify motor unit firing rates. Motor units were excluded using eight combinations of the reconstruct-and-test approach with accuracy thresholds of 0, 90, 91, and 92% with and without STA. The mean firing rate versus recruitment threshold relationship was minimally affected by STA. At 80% MVC, slopes acquired at the 0% accuracy threshold were significantly greater (i.e., less negative) than when 91% (p = .010) and 92% (p = .030) accuracy thresholds were applied. The application of STA has minimal influence on surface EMG signal decomposition results. Stringent reconstruct-and-test accuracy thresholds influence motor unit-derived relationships at high forces, perhaps explained through the increased presence of large motor unit action potentials. Investigators using the PDIII algorithm can expect negligible changes in motor unit-derived linear regression relationships with the application of secondary validation procedures.

Sex-Specific Reliability of Lower-Limb Corticospinal Excitability and Silent Periods.

ABSTRACT: Pagan, JI, Harmon, KK, Girts, RM, MacLennan, RJ, Beausejour, JP, Hernandez-Sarabia, JA, Coker, NA, Carr, JC, Ye, X, DeFreitas, JM, and Stock, MS. Sex-specific reliability of lower-limb corticospinal excitability and silent periods. J Strength Cond Res 37(9): 1882-1887, 2023-Transcranial magnetic stimulation (TMS) is a research tool that has potential to provide new insights into strength training-induced adaptations. However, using TMS to study the lower limbs is challenging, and sex-specific reliability has yet to be reported. We examined the reliability of corticospinal excitability and silent periods for the rectus femoris, vastus lateralis, and biceps femoris in both sexes. Thirteen males and 14 females reported to the laboratory twice. During both trials, a double cone coil was used to deliver 20 pulses to the rectus femoris hotspot with a stimulator output of 130% of active motor threshold. Motor-evoked potential peak-to-peak amplitude, which reflects corticospinal excitability, and silent period duration were quantified. Our results offer 4 novel findings. First, corticospinal excitability and silent period demonstrated higher reliability for the females. Second, regardless of sex and muscle, the silent period was more reliable than corticospinal excitability. Third, reliability was highest for our target muscle (rectus femoris), with lower reliability for the vastus lateralis and biceps femoris, suggesting that these methods cannot be used to study coactivation. Fourth, active motor threshold showed less variability than corticospinal excitability and silent period but increased at trial 2 in females. Many of the intraclass correlation coefficients were excellent (≥0.90), although we attribute this finding to variability between subjects. Reliability of lower-limb TMS measures may be sex, muscle, and variable dependent. Our findings suggest that both males and females should be included in lower-limb TMS research, although combining data between sexes should be approached cautiously.

The effects of resistance training to near failure on strength, hypertrophy, and motor unit adaptations in previously trained adults.

Limited research exists examining how resistance training to failure affects applied outcomes and single motor unit characteristics in previously trained individuals. Herein, resistance-trained adults (24 ± 3 years old, self-reported resistance training experience was 6 ± 4 years, 11 men and 8 women) were randomly assigned to either a low-repetitions-in-reserve (RIR; i.e., training near failure, n = 10) or high-RIR (i.e., not training near failure, n = 9) group. All participants implemented progressive overload during 5 weeks where low-RIR performed squat, bench press, and deadlift twice weekly and were instructed to end each training set with 0-1 RIR. high-RIR performed identical training except for being instructed to maintain 4-6 RIR after each set. During week 6, participants performed a reduced volume-load. The following were assessed prior to and following the intervention: (i) vastus lateralis (VL) muscle cross-sectional area (mCSA) at multiple sites; (ii) squat, bench press, and deadlift one-repetition maximums (1RMs); and (iii) maximal isometric knee extensor torque and VL motor unit firing rates during an 80% maximal voluntary contraction. Although RIR was lower in the low- versus high-RIR group during the intervention (p < 0.001), total training volume did not significantly differ between groups (p = 0.222). There were main effects of time for squat, bench press, and deadlift 1RMs (all p-values < 0.05), but no significant condition × time interactions existed for these or proximal/middle/distal VL mCSA data. There were significant interactions for the slope and y-intercept of the motor unit mean firing rate versus recruitment threshold relationship. Post hoc analyses indicated low-RIR group slope values decreased and y-intercept values increased after training suggesting low-RIR training increased lower-threshold motor unit firing rates. This study provides insight into how resistance training in proximity to failure affects strength, hypertrophy, and single motor unit characteristics, and may inform those who aim to program for resistance-trained individuals.

The influence of ultrasound image depth and gain on skeletal muscle echo intensity.

Echo intensity may associate with indicators of skeletal muscle quality, but investigators often use different methodological approaches that may alter echo intensity when acquiring B-mode ultrasound images. We examined the influence of image depth and gain settings on the interpretation of echo intensity. Thirty-six college-aged males and females participated. Ultrasound images of the vastus lateralis were captured in the sagittal plane. Images were captured at depths of 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, and 7.0 cm and gain settings of 50 and 60 dB in random order. For both gain settings, echo intensity values were similar between 4.0 and 6.0 cm. At a gain of 50 dB, 7.0 cm demonstrated greater values than all other depths. At a gain of 60 dB, 7.0 cm displayed greater values compared to all other depths, but 3.0 cm displayed lower echo intensity values than other depths. Echo intensity was substantially higher when using a gain of 60 dB compared to 50 dB (mean difference ≥ 21.7 arbitrary units, d ≥ 3.47). When planning investigations in new research areas, researchers should carefully consider their study-specific image depth. Echo intensity values are stable between depths of 4.0 and 6.0 cm, suggesting that changing image depth may not be problematic. Image gain must be kept constant. Novelty: Optimal approaches for B-mode ultrasound image acquisition of skeletal muscles remain unclear. Echo intensity is similar between depths of 4.0 and 6.0 cm, regardless of image gain. Investigators should seek to utilize a constant depth setting, but small deviations may be acceptable.

The acute effects of action observation on muscle strength/weakness and corticospinal excitability in older adults.

Muscle weakness is a critical problem facing many older adults. Interventions targeting nervous system plasticity may show promise in enhancing strength. The purpose of this study was to examine the acute effects of action observation on muscular strength characteristics and corticospinal excitability in older adults. Isometric wrist flexion strength characteristics and corticospinal excitability of the first dorsal interosseous (FDI) were measured in 14 older adults (mean age = 73 years) in response to observation of (1) STRONG contractions of the hand/wrist, (2) WEAK contractions of the hand/wrist, and (3) a CONTROL condition. Results from repeated measures analyses of variance (ANOVAs) indicated that rate of torque development at 200 ms (RTD200) significantly decreased from PRE to POST observation for CONTROL and WEAK, but not STRONG. No other ANOVAs were significant. However, effect sizes indicated that maximal voluntary contraction (MVC) peak torque showed moderate declines following WEAK (d = - 0.571) and CONTROL (d = - 0.636), but not STRONG (d = 0.024). Similarly, rate of torque development at 30 (RTD30), 50 (RTD50), and 200 (RTD200) ms showed large declines from PRE to POST after WEAK and CONTROL, but small changes following STRONG. FDI motor-evoked potential (MEP) amplitude tended to increase over time, but these results were variable. There was a pronounced effect from PRE to 8MIN (d = 0.954) during all conditions. Action observation of strong contractions may exert a preservatory effect on muscular strength. More work is needed to determine whether this is modulated by increased corticospinal excitability. The study was prospectively registered (ClinicalTrials.gov Identifier: NCT03946709).

The Influence of Sonographer Experience on Skeletal Muscle Image Acquisition and Analysis.

The amount of experience with ultrasonography may influence measurement outcomes while images are acquired or analyzed. The purpose of this study was to identify the interrater reliability of ultrasound image acquisition and image analysis between experienced and novice sonographers and image analysts, respectively. Following a brief hands-on training session (2 h), the experienced and novice sonographers and analysts independently performed image acquisition and analyses on the biceps brachii, vastus lateralis, and medial gastrocnemius in a sample of healthy participants (n = 17). Test-retest reliability statistics were computed for muscle thickness (transverse and sagittal planes), muscle cross-sectional area, echo intensity and subcutaneous adipose tissue thickness. The results show that image analysis experience generally has a greater impact on measurement outcomes than image acquisition experience. Interrater reliability for measurements of muscle size during image acquisition was generally good-excellent (ICC2,1: 0.82-0.98), but poor-moderate for echo intensity (ICC2,1: 0.43-0.77). For image analyses, interrater reliability for measurements of muscle size for the vastus lateralis and biceps brachii was poor-moderate (ICC2,1: 0.48-0.70), but excellent for echo intensity (ICC2,1: 0.90-0.98). Our findings have important implications for laboratories and clinics where members possess varying levels of ultrasound experience.

2D projection image reconstruction for field free line single-sided magnetic particle imaging scanner: simulation studies.

Magnetic Particle Imaging is an imaging modality that exploits the nonlinear response of superparamagnetic iron oxide nanoparticles to a time-varying magnetic field. In the past years, various scanner topologies have been proposed, which includes a single-sided scanner. Such a scanner features all its hardware located on one side, offering accessibility without limitations due to the size of the object of interest. In this paper, we present a proof of concept image reconstruction simulation studies for a single-sided field-free line scanner utilizing non-uniform magnetic fields. Specifically, we implemented a filtered backprojection algorithm allowing a 2D image reconstruction over a field of view of 4 × 4 cm2 with a spatial resolution of up to 2 mm for noiseless case.

Single-Sided Magnetic Particle Imaging Device with Field-Free-Line Geometry for in-vivo Imaging Applications.

Magnetic Particle Imaging (MPI) has shown great promise to surpass existing in vivo imaging modalities in some clinical applications. However, one of the challenges to MPI being translated into clinical practice has been the ability to scale up the selection field coils to surround a human body while being able to generate and drive a sufficiently strong magnetic field gradient. These requirements impose safety concerns as well as prohibitively high-power consumption in devices with large cylindrical volume. Therefore, we consider an alternative approach such as a single-sided topology, in which all the hardware is located on one side of the imaging volume accommodating larger subjects. Moreover, different from the previously implemented field-free point single-sided scanners, we realized a field-free line geometry providing, in principle, factor of ten higher signal and benefiting from a more robust back-projection image reconstruction technique. In this work, we present and characterize a first prototype of a single-sided MPI device with field-free-line geometry suited for in-vivo imaging of small animals as well as regions of interest in humans.

WNKs are potassium-sensitive kinases.

With no lysine (K) (WNK) kinases regulate epithelial ion transport in the kidney to maintain homeostasis of electrolyte concentrations and blood pressure. Chloride ion directly binds WNK kinases to inhibit autophosphorylation and activation. Changes in extracellular potassium are thought to regulate WNKs through changes in intracellular chloride. Prior studies demonstrate that in some distal nephron epithelial cells, intracellular potassium changes with chronic low- or high-potassium diet. We, therefore, investigated whether potassium regulates WNK activity independent of chloride. We found decreased activity of Drosophila WNK and mammalian WNK3 and WNK4 in fly Malpighian (renal) tubules bathed in high extracellular potassium, even when intracellular chloride was kept constant at either ∼13 mM or 26 mM. High extracellular potassium also inhibited chloride-insensitive mutants of WNK3 and WNK4. High extracellular rubidium was also inhibitory and increased tubule rubidium. The Na+/K+-ATPase inhibitor, ouabain, which is expected to lower intracellular potassium, increased tubule Drosophila WNK activity. In vitro, potassium increased the melting temperature of Drosophila WNK, WNK1, and WNK3 kinase domains, indicating ion binding to the kinase. Potassium inhibited in vitro autophosphorylation of Drosophila WNK and WNK3, and also inhibited WNK3 and WNK4 phosphorylation of their substrate, Ste20-related proline/alanine-rich kinase (SPAK). The greatest sensitivity of WNK4 to potassium occurred in the range of 80-180 mM, encompassing physiological intracellular potassium concentrations. Together, these data indicate chloride-independent potassium inhibition of Drosophila and mammalian WNK kinases through direct effects of potassium ion on the kinase.

TRPV1 temperature activation is specifically sensitive to strong decreases in amino acid hydrophobicity.

Several transient receptor potential (TRP) ion channels can be directly activated by hot or cold temperature with high sensitivity. However, the structures and molecular mechanism giving rise to their high temperature sensitivity are not fully understood. One hypothesized mechanism assumes that temperature activation is driven by the exposure of hydrophobic residues to solvent. This mechanism further predicts that residues are exposed to solvent in a coordinated fashion, but without necessarily being located in close proximity to each other. However, there is little experimental evidence supporting this mechanism in TRP channels. Here, we combined high-throughput mutagenesis, functional screening, and deep sequencing to identify mutations from a total of ~7,300 TRPV1 random mutant clones. We found that strong decreases in hydrophobicity of amino acids are better tolerated for activation by capsaicin than for activation by hot temperature, suggesting that strong hydrophobicity might be specifically required for temperature activation. Altogether, our work provides initial correlative support for a previously hypothesized temperature mechanism in TRP ion channels.

Directionality of temperature activation in mouse TRPA1 ion channel can be inverted by single-point mutations in ankyrin repeat six.

Several transient receptor potential (TRP) ion channels are activated with high sensitivity by either cold or hot temperatures. However, structures and mechanism that determine temperature directionality (cold versus heat) are not established. Here we screened 12,000 random mutant clones of the cold-activated mouse TRPA1 ion channel with a heat stimulus. We identified three single-point mutations that are individually sufficient to make mouse TRPA1 warm activated, while leaving sensitivity to chemicals unaffected. Mutant channels have high temperature sensitivity of voltage activation, specifically of channel opening, but not channel closing, which is reminiscent of other heat-activated TRP channels. All mutations are located in ankyrin repeat six, which identifies this domain as a sensitive modulator of thermal activation. We propose that a change in the coupling of temperature sensing to channel gating generates this sensitivity to warm temperatures. Our results demonstrate that minimal changes in protein sequence are sufficient to generate a wide diversity of thermal sensitivities in TRPA1.

Allelic specificity of Ube3a expression in the mouse brain during postnatal development.

Genetic alterations of the maternal UBE3A allele result in Angelman syndrome (AS), a neurodevelopmental disorder characterized by severe developmental delay, lack of speech, and difficulty with movement and balance. The combined effects of maternal UBE3A mutation and cell type-specific epigenetic silencing of paternal UBE3A are hypothesized to result in a complete loss of functional UBE3A protein in neurons. However, the allelic specificity of UBE3A expression in neurons and other cell types in the brain has yet to be characterized throughout development, including the early postnatal period when AS phenotypes emerge. Here we define maternal and paternal allele-specific Ube3a protein expression throughout postnatal brain development in the mouse, a species that exhibits orthologous epigenetic silencing of paternal Ube3a in neurons and AS-like behavioral phenotypes subsequent to maternal Ube3a deletion. We find that neurons downregulate paternal Ube3a protein expression as they mature and, with the exception of neurons born from postnatal stem cell niches, do not express detectable paternal Ube3a beyond the first postnatal week. By contrast, neurons express maternal Ube3a throughout postnatal development, during which time localization of the protein becomes increasingly nuclear. Unlike neurons, astrocytes and oligodendrotyes biallelically express Ube3a. Notably, mature oligodendrocytes emerge as the predominant Ube3a-expressing glial cell type in the cortex and white matter tracts during postnatal development. These findings demonstrate the spatiotemporal characteristics of allele-specific Ube3a expression in key brain cell types, thereby improving our understanding of the developmental parameters of paternal Ube3a silencing and the cellular basis of AS.

Surface-mediated production of hydroxyl radicals as a mechanism of iron oxide nanoparticle biotoxicity.

Emerging applications of nanosized iron oxides in nanotechnology introduce vast quantities of nanomaterials into the human environment, thus raising some concerns. Here we report that the surface of γ-Fe(2)O(3) nanoparticles 20-40 nm in diameter mediates production of highly reactive hydroxyl radicals (OH(•)) under conditions of the biologically relevant superoxide-driven Fenton reaction. By conducting comparative spin-trapping EPR experiments, we show that the free radical production is attributed primarily to the catalytic reactions at the nanoparticles' surface rather than being caused by the dissolved metal ions released by the nanoparticles as previously thought. Moreover, the catalytic centers on the nanoparticle surface were found to be at least 50-fold more effective in OH(•) radical production than the dissolved Fe(3+) ions. Conventional surface modification methods such as passivating the nanoparticles' surface with up to 935 molecules of oleate or up to 18 molecules of bovine serum albumin per iron oxide core were found to be rather ineffective in suppressing production of the hydroxyl radicals. The experimental protocols developed in this study could be used as one of the approaches for developing analytical assays for assessing the free radical generating activity of a variety of nanomaterials that is potentially related to their biotoxicity.

Gender differences in friends' influences on adolescent drinking: a genetic epidemiological study.

BACKGROUND: We use data from a population-based twin study to examine the association between characteristics of the friendship group and adolescents' own alcohol use at age 14, with focus on gender differences, both with respect to the adolescent's own gender and the gender composition of his/her friendship group. METHODS: (1) We conducted analyses on the full epidemiological sample of individuals to determine the magnitude of association between friendship characteristics and alcohol use, and to test for interaction with gender and gender of friends. (2) We used the twin structure of the dataset to study the extent to which similarity in drinking behaviors between adolescents and their friends was due to shared genetic and/or environmental pathways. RESULTS: Friends' drinking, smoking, and delinquency were more strongly related to alcohol use in girls, compared to boys, and in adolescents with opposite-sex friends, compared to adolescents with only same-sex friends. Friends' alcohol use showed modest evidence of genetic influence in girls, suggesting peer selection; however, there was no evidence of genetic influence on friends' alcohol use in boys. The correlation between adolescent and friend drinking was largely attributable to shared environmental effects across genders. CONCLUSIONS: Gender and gender of friends moderate the associations between friends' behavior and adolescents' alcohol use, with evidence that girls, and those with opposite-sex friends, may be more susceptible to friends' influence. Genetically informative analyses suggest that similarity in alcohol use between adolescents and their friends is mediated, at least partially, through environmental pathways.

Changing environmental influences on substance use across development.

In contrast to many phenotypes that have been studied using twin designs, substance use shows considerable evidence of environmental influence. Accordingly, specifying the relevant environments and understanding the nature of their effects is an important research priority. Twin studies also have demonstrated that the importance of genetic and environmental influences varies across development for a variety of behavioral outcomes, including substance use. Here, we report analyses exploring moderating effects associated with parenting and peer characteristics on adolescent smoking and drinking, measured at ages 14 and 17. We find significant evidence of moderating effects associated with two dimensions of parenting (parental monitoring and time spent in activities with parents) on adolescent smoking, measured at two time points across development, but no moderating effects on adolescent drinking. Genetic influences on smoking increased, and common environmental effects decreased, as adolescents reported less parental monitoring and spending more time with their parents. Conversely, we find evidence that adolescent drinking is more strongly influenced by peer characteristics. The importance of genetic predispositions was increased among adolescents who reported more friends who used alcohol. These analyses illustrate the importance of incorporating measured aspects of the environment into genetically informative twin models to begin to understand how specific environments are related to various outcomes. Furthermore, they illustrate the importance of using a developmental perspective to understand how specific influences may vary across different ages, and across different phenotypes.