Benefits of caloric restriction in the myenteric neuronal plasticity in aging rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

THE PERCEPTION AND UNDERSTANDING OF HEALTH PROFESSIONALS AND UNDERGRADUATE STUDENTS REGARDING AGING AND THE ELDERLY

This qualitative study was developed with 117 healthcare professionals and undergraduate students who were participants of a non-verbal communication training program in gerontology, with the objective to identify the perception and understanding of healthcare undergraduates and graduates regarding aging and the elderly. The results allowed the construction of the following categories: an evolution of life that brings a variety of experiences; natural, mysterious and with accumulated experiences; a decrease in overall happiness due to an increase in isolation; a time of valuing affection and respect; an inevitable stage including distress, prejudice, and limitations worthy of attention; a natural consequence of life; and the presence of disease and the global physiological process. Regarding perceptions of the elderly, the answers were classified as positive, negative, mixed and neutral. We considered that the understanding regarding the elderly and aging was limited and pessimist, indicating a need to become aware that one's views affect the way we relate to others.

Morphological and functional study of cerebral aging in rat

Aging is a physiological process characterized by a progressive decline of the “cellular homeostatic reserve”, refereed as the capability to respond suitably to exogenous and endogenous stressful stimuli. Due to their high energetic requests and post-mitotic nature, neurons are peculiarly susceptible to this phenomenon. However, the aged brain maintains a certain level of adaptive capacities and if properly stimulated may warrant a considerable functional recovery. Aim of the present research was to verify the plastic potentialities of the aging brain of rats subjected to two kind of exogenous stimuli: A) the replacement of the standard diet with a ketogenic regimen (the change forces the brain to use ketone bodies (KB) in alternative to glucose to satisfy the energetic needs) and B) a behavioural task able to induce the formation of inhibitory avoidance memory. A) Fifteen male Wistar rats of 19 months of age were divided into three groups (average body weight pair-matched), and fed for 8 weeks with different dietary regimens: i) diet containing 10% medium chain triglycerides (MCT); ii) diet containing 20% MCT; iii) standard commercial chow. Five young (5 months of age) and five old (26-27 months of age) animals fed with the standard diet were used as further controls. The following morphological parameters reflecting synaptic plasticity were evaluated in the stratum moleculare of the hippocampal CA1 region (SM CA1), in the outer molecular layer of the hippocampal dentate gyrus (OML DG), and in the granule cell layer of the cerebellar cortex (GCL-CCx): average area (S), numeric density (Nvs), and surface density (Sv) of synapses, and average volume (V), numeric density (Nvm), and volume density (Vv) of synaptic mitochondria. Moreover, succinic dehydrogenase (SDH) activity was cytochemically determined in Purkinje cells (PC) and V, Nvm, Vv, and cytochemical precipitate area/mitochondrial area (R) of SDH-positive mitochondria were evaluated. In SM CA1, MCT-KDs induced the early appearance of the morphological patterns typical of old animals: higher S and V, and lower Nvs and Nvm. On the contrary, in OML DG, Sv and Vv of MCT-KDs-fed rats were higher (as a result of higher Nvs and Nvm) vs. controls; these modifications are known to improve synaptic function and metabolic supply. The opposite effects of MCT-KDs might reflect the different susceptibility of these brain regions to the aging processes: OML DG is less vulnerable than SM CA1, and the reactivation of ketone bodies uptake and catabolism might occur more efficiently in this region, allowing the exploitation of their peculiar metabolic properties. In GCL-CCx, the results described a new scenario in comparison to that found in the hippocampal formation: 10%MCT-KD induced the early appearance of senescent patterns (decreased Nvs and Nvm; increased V), whereas 20%MCT-KD caused no changes. Since GCL-CCx is more vulnerable to age than DG, and less than CA1, these data further support the hypothesis that MCT-KDs effects in the aging brain critically depend on neuronal vulnerability to age, besides MCT percentage. Regarding PC, it was decided to evaluate only the metabolic effect of the dietetic regimen (20%MCT-KD) characterized by less side effects. KD counteracted age-related decrease in numeric density of SDH-positive mitochondria, and enhanced their energetic efficiency (R was significantly higher in MCT-KD-fed rats vs. all the controls). Since it is well known that Purkinje and dentate gyrus cells are less vulnerable to aging than CA1 neurons, these results corroborate our previous hypothesis. In conclusion, the A) experimental line provides the first evidence that morphological and functional parameters reflecting synaptic plasticity and mitochondrial metabolic competence may be modulated by MCT-KDs in the pre-senescent central nervous system, and that the effects may be heterogeneous in different brain regions. MCT-KDs seem to supply high energy metabolic intermediates and to be beneficial (“anti-aging”) for those neurons that maintain the capability to exploit them. This implies risks but also promising potentialities for the therapeutic use of these diets during aging B) Morphological parameters of synapses and synaptic mitochondria in SM CA1 were investigated in old (26-27 month-old) female Wistar rats following a single trial inhibitory avoidance task. In this memory protocol animals learn to avoid a dark compartment in which they received a mild, inescapable foot-shock. Rats were tested 3 and 6 or 9 hours after the training, divided into good and bad responders according to their performance (retention times above or below 100 s, respectively) and immediately sacrificed. Nvs, S, Sv, Nvm, V, and Vv were evaluated. In the good responder group, the numeric density of synapses and mitochondria was significantly higher and the average mitochondrial volume was significantly smaller 9 hours vs. 6 hours after the training. No significant differences were observed among bad responders. Thus, better performances in passive avoidance memory task are correlated with more efficient plastic remodeling of synaptic contacts and mitochondria in hippocampal CA1. These findings indicate that maintenance of synaptic plastic reactivity during aging is a critical requirement for preserving long-term memory consolidation.

Outdoor bronze conservation: assessment of protective treatments by accelerated aging and of treatment removal procedures by laser cleaning

Outdoor bronzes exposed to the environment form naturally a layer called patina, which may be able to protect the metallic substrate. However, since the last century, with the appearance of acid rains, a strong change in the nature and properties of the copper based patinas occurred [1]. Studies and general observations have established that bronze corrosion patinas created by acid rain are not only disfiguring in terms of loss of detail and homogeneity, but are also unstable [2]. The unstable patina is partially leached away by rainwater. This leaching is represented by green streaking on bronze monuments [3]. Because of the instability of the patina, conservation techniques are usually required. On a bronze object exposed to the outdoor environment, there are different actions of the rainfall and other atmospheric agents as a function of the monument shape. In fact, we recognize sheltered and unsheltered areas as regards exposure to rainwater [4]. As a consequence of these different actions, two main patina types are formed on monuments exposed to the outdoor environment. These patinas have different electrochemical, morphological and compositional characteristics [1]. In the case of sheltered areas, the patina contains mainly copper products, stratified above a layer strongly enriched in insoluble Sn oxides, located at the interface with the uncorroded metal. Moreover, different colors of the patina result from the exposure geometry. The surface color may be pale green for unsheltered areas, and green and mat black for sheltered areas [4]. Thus, in real outdoor bronze monuments, the corrosion behavior is strongly influenced by the exposure geometry. This must be taken into account when designing conservation procedures, since the patina is in most cases the support on which corrosion inhibitors are applied. Presently, for protecting outdoor bronzes against atmospheric corrosion, inhibitors and protective treatments are used. BTA and its derivatives, which are the most common inhibitors used for copper and its alloy, were found to be toxic for the environment and human health [5, 6]. Moreover, it has been demonstrated that BTA is efficient when applied on bare copper but not as efficient when applied on bare bronze [7]. Thus it was necessary to find alternative compounds. Silane-based inhibitors (already successfully tested on copper and other metallic substrates [8]), were taken into consideration as a non-toxic, environmentally friendly alternative to BTA derivatives for bronze protection. The purpose of this thesis was based on the assessment of the efficiency of a selected compound, to protect the bronze against corrosion, which is the 3-mercapto-propyl-trimethoxy-silane (PropS-SH). It was selected thanks to the collaboration with the Corrosion Studies Centre “Aldo Daccò” at the Università di Ferrara. Since previous studies [9, 10, 11] demonstrated that the addition of nanoparticles to silane-based inhibitors leads to an increase of the protective efficiency, we also wanted to evaluate the influence of the addition of CeO2, La2O3, TiO2 nanoparticles on the protective efficiency of 3-mercapto-propyl-trimethoxy-silane, applied on pre-patinated bronze surfaces. This study is the first section of the thesis. Since restorers have to work on patinated bronzes and not on bare metal (except for contemporary art), it is important to be able to recreate the patina, under laboratory conditions, either in sheltered or unsheltered conditions to test the coating and to obtain reliable results. Therefore, at the University of Bologna, different devices have been designed to simulate the real outdoor conditions and to create a patina which is representative of real application conditions of inhibitor or protective treatments. In particular, accelerated ageing devices by wet & dry (simulating the action of stagnant rain in sheltered areas [12]) and by dropping (simulating the leaching action of the rain in unsheltered areas [1]) tests were used. In the present work, we used the dropping test as a method to produce pre-patinated bronze surfaces for the application of a candidate inhibitor as well as for evaluating its protective efficiency on aged bronze (unsheltered areas). In this thesis, gilded bronzes were also studied. When they are exposed to the outside environment, a corrosion phenomenon appears which is due to the electrochemical couple gold/copper where copper is the anode. In the presence of an electrolyte, this phenomenon results in the formation of corrosion products than will cause a blistering of the gold (or a break-up and loss of the film in some cases). Moreover, because of the diffusion of the copper salts to the surface, aggregates and a greenish film will be formed on the surface of the sample [13]. By coating gilded samples with PropS-SH and PropS-SH containing nano-particles and carrying out accelerated ageing by the dropping test, a discussion is possible on the effectiveness of this coating, either with nano-particles or not, against the corrosion process. This part is the section 2 of this thesis. Finally, a discussion about laser treatment aiming at the assessment of reversibility/re-applicability of the PropS-SH coating can be found in section 3 of this thesis. Because the protective layer loses its efficiency with time, it is necessary to find a way of removing the silane layer, before applying a new one on the “bare” patina. One request is to minimize the damages that a laser treatment would create on the patina. Therefore, different laser fluences (energy/surface) were applied on the sample surface during the treatment process in order to find the best range of fluence. In particular, we made a characterization of surfaces before and after removal of PropS-SH (applied on a naturally patinated surface, and subsequently aged by natural exposure) with laser methods. The laser removal treatment was done by the CNR Institute of Applied Physics “Nello Carrara” of Sesto Fiorentino in Florence. In all the three sections of the thesis, a range of non-destructive spectroscopic methods (Scanning Electron Microscopy with Energy Dispersive Spectroscopy (SEM-EDS), μ-Raman spectroscopy, X-Ray diffractometry (XRD)) were used for characterizing the corroded surfaces. AAS (Atomic Absorption Spectroscopy) was used to analyze the ageing solutions from the dropping test in sections 1 and 2.

Aging in human liver and skeletal muscle: studies on proteasomes

Aging is a complex phenomenon that affects organs and tissues at a different rate. With advancing age, the skeletal muscle undergoes a progressive loss of mass and strength, a process known as sarcopenia that leads to a decreased mobility and increased risk of falls and invalidity. On the other side, another organ such as the liver that is endowed with a peculiar regenerative capacity seems to be only marginally affected by aging. Accordingly, clinical data indicate that liver transplantation from aged subjects has, in specific conditions, function and duration comparable to those achievable with grafts of liver from young donors. The molecular mechanisms involved in these peculiar aging patterns are still largely unknown, but it is conceivable that protein degradation machineries might play an important role, as they are responsible for the maintenance of cellular homeostasis. Indeed, it has been suggested that alteration of proteostasis may contribute to the onset and progression of several age-related pathological conditions, including skeletal muscle wasting and sarcopenia, as well as to the aging phenotypes. The ubiquitin-proteasome system (UPS) is one of the most important cellular pathways for intracellular degradation of short-lived as well as damaged proteins. To date, studies on the age-related modifications of proteasomes in liver and skeletal muscle were performed prevalently in rodents, with controversial results, while only preliminary observations have been obtained in human liver and skeletal muscle. In this scenario, we want to investigate and characterize in humans the age-related modifications of proteasomes of these two different organs.

Polymeric membranes for CO2 separation: effect of aging, humidity and facilitated transport

Polymeric membranes represent a promising technology for gas separation processes, thanks to low costs, reduced energy consumption and limited waste production. The present thesis aims at studying the transport properties of two membrane materials, suitable for CO2 purification applications. In the first part, a polyimide, Matrimid 5218, has been throughout investigated, with particular reference to the effect of thermal treatment, aging and the presence of water vapor in the gas transport process. Permeability measurements showed that thermal history affects relevantly the diffusion of gas molecules across the membrane, influencing also the stability of the separation performances. Subsequently, the effect of water on Matrimid transport properties has been characterized for a wide set of incondensable penetrants. A monotonous reduction of permeability took place at increasing the water concentration within the polymer matrix, affecting the investigated gaseous species to the same extent, despite the different thermodynamic and kinetic features. In this view, a novel empirical model, based on the Free Volume Theory, has been proposed to qualitatively describe the phenomenon. Moreover, according to the accurate representation of the experimental data, the suggested approach has been combined with a more rigorous thermodynamic tool (NELF Model), allowing an exhaustive description of water influence on the single parameters contributing to the gas permeation across the membrane. In the second part, the study has focused on the synthesis and characterization of facilitated transport membranes, able to achieving outstanding separation performances thanks to the chemical enhancement of CO2 permeability. In particular, the transport properties have been investigated for high pressure CO2 separation applications and specific solutions have been proposed to solve stability issues, frequently arising under such severe conditions. Finally, the effect of different process parameters have been investigated, aiming at the identification of the optimal conditions capable to maximize the separation performance.

Metabolomics Reveals Aging-associated Attenuation of Noninvasive Radiation Biomarkers in Mice: Potential Role of Polyamine Catabolism and Incoherent DNA Damage-repair

Development of methods for rapid screening and stratification of subjects after exposure is an integral part of countermeasures against radiation. The potential demographic and exposure history-related heterogeneity of exposed populations warrants robust biomarkers that withstand and reflect such differences. In this study, the effect of aging and repeated exposure on the metabolic response to sublethal irradiation was examined in mice using UPLC-ESI-QTOF mass spectrometry. Aging attenuated postexposure elevation in excretions of DNA damage biomarkers as well as N(1)-acetylspermidine. Although N(1)-acetylspermidine and 2'-deoxyuridine elevation was highly correlated in all age groups, xanthine and N(1)-acetylspermidine elevation was poorly correlated in older mice. These results may reflect the established decline in DNA damage-repair efficiency associated with aging and indicate a novel role for polyamine metabolism in the process. Although repeated irradiation at long intervals did not affect the elevation of N(1)-acetylspermidine, 2'-deoxyuridine, and xanthine, it did significantly attenuate the elevation of 2'-deoxycytidine and thymidine compared to a single exposure. However, these biomarkers were found to identify exposed subjects with accuracy ranging from 82% (xanthosine) to 98% (2'-deoxyuridine), irrespective of their age and exposure history. This indicates that metabolic biomarkers can act as robust noninvasive signatures of sublethal radiation exposure.

Corporate aging and investment decisions

Paper I: Corporate aging and internal resource allocation Abstract Various observers argue that established firms are at a disadvantage in pursuing new growth opportunities. In this paper, we provide systematic evidence that established firms allocate fewer resources to high-growth lines of business. However, we find no evidence of inefficient resource allocation in established firms. Redirecting resources from high-growth to low-growth lines of business does not result in lower profitability. Also, resource allocation towards new growth opportunities does not increase when managers of established firms are exposed to takeover and product market threats. Rather, it seems that conservative resource allocation strategies are driven by pressures to meet investors’ expectations. Our empirical evidence, thus, favors the hypothesis that established firms wisely choose to allocate fewer resources to new growth opportunities as external pressures force them to focus on efficiency rather than novelty (Holmström 1989). Paper II: Corporate aging and asset sales Abstract This paper asks whether divestitures are motivated by strategic considerations about the scope of the firm’s activities. Limited managerial capacity implies that exploiting core competences becomes comparatively more attractive than exploring new growth opportunities as firms mature. Divestitures help stablished firms free management time and increase the focus on core competences. The testable implication of this attention hypothesis is that established firms are the main sellers of assets, that their divestiture activity increases when managerial capacity is scarcer, that they sell non-core activities, and that they return the divestiture proceeds to the providers of capital instead of reinvesting them in the firm. We find strong empirical support for these predictions. Paper III: Corporate aging and lobbying expenditures Abstract Creative destruction forces constantly challenge established firms, especially in competitive markets. This paper asks whether corporate lobbying is a competitive weapon of established firms to counteract the decline in rents over time. We find a statistically and economically significant positive relation between firm age and lobbying expenditures. Moreover, the documented age-effect is weaker when firms have unique products or operate in concentrated product markets. To address endogeneity, we use industry distress as an exogenous nonlegislative shock to future rents and show that established firms are relatively more likely to lobby when in distress. Finally, we provide empirical evidence that corporate lobbying efforts by established firms forestall the creative destruction process. In sum, our findings suggest that corporate lobbying is a competitive weapon of established firms to retain profitability in competitive environments.

Switch from monoallelic to biallelic human IGF2 promoter methylation during aging and carcinogenesis.

We have previously linked aging, carcinogenesis, and de novo methylation within the promoter of the estrogen receptor (ER) gene in human colon. We now examine the dynamics of this process for the imprinted gene for insulin-like growth factor II (IGF2). In young individuals, the P2-4 promoters of IGF2 are methylated exclusively on the silenced maternal allele. During aging, this promoter methylation becomes more extensive and involves the originally unmethylated allele. Most adult human tumors, including colon, breast, lung, and leukemias, exhibit increased methylation at the P2-4 IGF2 promoters, suggesting further spreading during the neoplastic process. In tumors, this methylation is associated with diminished or absent IGF2 expression from the methylated P3 promoter but maintained expression from P1, an upstream promoter that is not contained within the IGF2 CpG island. Our results demonstrate a remarkable evolution of methylation patterns in the imprinted promoter of the IGF2 gene during aging and carcinogenesis, and provide further evidence for a potential link between aberrant methylation and diseases of aging.

Cellular aging, destabilization, and cancer.

Three major characteristics of aging in animals are a slowdown of cell proliferation, an increase in residual bodies associated with age pigments, and a marked increase in the likelihood of neoplastic transformation. The 28 L subline of the NIH 3T3 line of mouse embryo fibroblasts exhibits all these characteristics when held at confluence for extended periods. The impairment of proliferation is the first behavioral characteristic detected in low density subcultures from the confluent cultures, and it persists through many cell generations of exponential multiplication. There is an equal degree of growth impairment among replicate cultures (lineages) recovered after each of 2 successive rounds of confluence, although heterogeneity appears after the third round. The growth impairment pervades the entire cell population of each lineage. The degree and duration of impairment increase with repeated rounds of confluence. A marked increase of residual bodies characteristic of age pigments occurs in the cytoplasm of all the cells kept under prolonged confluence. Neoplastic transformation first appears as foci of multilayered cells on a monolayered background of nontransformed cells. The transformed cells arise at different times in the lineages and originate from a very small fraction of the population. The transformed cells selectively overgrow the entire population in successive rounds of confluence leading to an increase in saturation density of each lineage at different times. Under cloning conditions, isolated colonies of transformed cells develop more slowly than colonies of nontransformed cells but eventually reach a higher population density. The regularity of persistent growth impairment among the lineages and the appearance of large numbers of residual bodies in all the cells of each population are more characteristic of an epigenetic process than of specific local mutations. although random chromosomal lesions cannot be ruled out. By contrast, the low frequency and stochastic character of neoplastic transformation are consistent with a conventional genetic origin. The advent in long-term confluent NIH 3T3 cultures of three cardinal characteristics of cellular aging in vivo recommends it as a model for aging cells.

A biomarker that identifies senescent human cells in culture and in aging skin in vivo.

Normal somatic cells invariably enter a state of irreversibly arrested growth and altered function after a finite number of divisions. This process, termed replicative senescence, is thought to be a tumor-suppressive mechanism and an underlying cause of aging. There is ample evidence that escape from senescence, or immortality, is important for malignant transformation. By contrast, the role of replicative senescence in organismic aging is controversial. Studies on cells cultured from donors of different ages, genetic backgrounds, or species suggest that senescence occurs in vivo and that organismic lifespan and cell replicative lifespan are under common genetic control. However, senescent cells cannot be distinguished from quiescent or terminally differentiated cells in tissues. Thus, evidence that senescent cells exist and accumulate with age in vivo is lacking. We show that several human cells express a beta-galactosidase, histochemically detectable at pH 6, upon senescence in culture. This marker was expressed by senescent, but not presenescent, fibroblasts and keratinocytes but was absent from quiescent fibroblasts and terminally differentiated keratinocytes. It was also absent from immortal cells but was induced by genetic manipulations that reversed immortality. In skin samples from human donors of different age, there was an age-dependent increase in this marker in dermal fibroblasts and epidermal keratinocytes. This marker provides in situ evidence that senescent cells may exist and accumulate with age in vivo.

Effect of aging on yield stress and corrosion resistance of die cast magnesium alloy

Corrosion resistance is an important property that could be affected by the ageing process. In order to investigate whether aging affects the corrosion resistance, corrosion rate and yield strength of diecast magnesium alloy AZ91D were measured and analysed after ageing. It was found that the dependence of the corrosion rate on ageing time can be ascribed to the changes in microstructure of the alloy and chemical composition of its matrix. Precipitation of the P phase (Mg17Al12) occurred along the grain boundaries during the initial ageing stages, resulting in a decreasing corrosion rate and an inceasing yield strength. In the later stages, the decreasing aluminium content in the alpha matrix made it more active, causing an increase in the corrosion rate. The decrease in aluminium content in the matrix also leads to a decrease in yield strength.

A role for epigenetic modulation of the innate immune response during aging

The ageing process results from a complex interplay between genes and the environment that can precipitate an uncontrolled inflammation. Epigenetic changes are believed to provide a link between the environment and nutrition to gene expression by altering the activity of some histone-modifying protein. Epigenetic modifications of DNA and histone proteins have been proposed as important contributory mechanisms to the retention of metabolic memory over time. A thorough understanding of the posttranscriptional and epigenetic factors involved in both normal ageing and age-related disease may inform new strategies and approaches to diagnose, treat, or suppress many aspects of age-dependent frailty.

The effects of aging on the BTBR mouse model of autism spectrum disorder.

Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder characterized by alterations in social functioning, communicative abilities, and engagement in repetitive or restrictive behaviors. The process of aging in individuals with autism and related neurodevelopmental disorders is not well understood, despite the fact that the number of individuals with ASD aged 65 and older is projected to increase by over half a million individuals in the next 20 years. To elucidate the effects of aging in the context of a modified central nervous system, we investigated the effects of age on the BTBR T + tf/j mouse, a well characterized and widely used mouse model that displays an ASD-like phenotype. We found that a reduction in social behavior persists into old age in male BTBR T + tf/j mice. We employed quantitative proteomics to discover potential alterations in signaling systems that could regulate aging in the BTBR mice. Unbiased proteomic analysis of hippocampal and cortical tissue of BTBR mice compared to age-matched wild-type controls revealed a significant decrease in brain derived neurotrophic factor and significant increases in multiple synaptic markers (spinophilin, Synapsin I, PSD 95, NeuN), as well as distinct changes in functional pathways related to these proteins, including "Neural synaptic plasticity regulation" and "Neurotransmitter secretion regulation." Taken together, these results contribute to our understanding of the effects of aging on an ASD-like mouse model in regards to both behavior and protein alterations, though additional studies are needed to fully understand the complex interplay underlying aging in mouse models displaying an ASD-like phenotype.

EFFECTS OF AGING ON MIDBRAIN AND CORTICAL SPEECH-IN-NOISE PROCESSING

Older adults frequently report that they can hear what they have been told but cannot understand the meaning. This is particularly true in noisy conditions, where the additional challenge of suppressing irrelevant noise (i.e. a competing talker) adds another layer of difficulty to their speech understanding. Hearing aids improve speech perception in quiet, but their success in noisy environments has been modest, suggesting that peripheral hearing loss may not be the only factor in the older adult’s perceptual difficulties. Recent animal studies have shown that auditory synapses and cells undergo significant age-related changes that could impact the integrity of temporal processing in the central auditory system. Psychoacoustic studies carried out in humans have also shown that hearing loss can explain the decline in older adults’ performance in quiet compared to younger adults, but these psychoacoustic measurements are not accurate in describing auditory deficits in noisy conditions. These results would suggest that temporal auditory processing deficits could play an important role in explaining the reduced ability of older adults to process speech in noisy environments. The goals of this dissertation were to understand how age affects neural auditory mechanisms and at which level in the auditory system these changes are particularly relevant for explaining speech-in-noise problems. Specifically, we used non-invasive neuroimaging techniques to tap into the midbrain and the cortex in order to analyze how auditory stimuli are processed in younger (our standard) and older adults. We will also attempt to investigate a possible interaction between processing carried out in the midbrain and cortex.