Different Aspects Of Aging Research Articles

Hydroxycitrate delays early mortality in mice and promotes muscle regeneration while inducing a rich hepatic energetic status.

ATP citrate lyase (ACLY) inhibitors have the potential of modulating central processes in protein, carbohydrate, and lipid metabolism, which can have relevant physiological consequences in aging and age-related diseases. Here, we show that hepatic phospho-active ACLY correlates with overweight and Model for End-stage Liver Disease score in humans. Wild-type mice treated chronically with the ACLY inhibitor potassium hydroxycitrate exhibited delayed early mortality. In AML12 hepatocyte cultures, the ACLY inhibitors potassium hydroxycitrate, SB-204990, and bempedoic acid fostered lipid accumulation, which was also observed in the liver of healthy-fed mice treated with potassium hydroxycitrate. Analysis of soleus tissue indicated that potassium hydroxycitrate produced the modulation of wound healing processes. Invivo, potassium hydroxycitrate modulated locomotor function toward increased wire hang performance and reduced rotarod performance in healthy-fed mice, and improved locomotion in mice exposed to cardiotoxin-induced muscle atrophy. Our findings implicate ACLY and ACLY inhibitors in different aspects of aging and muscle regeneration.

Understanding What Older People Value in the Design of a Community-Based Healthy Ageing Program, a Qualitative Study

Older people who are wanting to support their own ability to age well may benefit from attending community-based group programs. However, many of these programs are designed and implemented by health professionals without direct input from older people, which may limit the opportunity to ensure such programs are authentically meeting the needs of this population group. A qualitative approach, using an interpretative phenomenological analysis (IPA), was undertaken with seven (six female and one male) participants, aged between 62 and 80 years to explore the experiences of participating in a pilot Ageing Well Program. Interviews were transcribed and analysed according to IPA principles. Three themes emerged from the analysis of the interview data: (1) The value of focusing on different aspects of ageing; (2) Learning new knowledge; and (3) Transferring skills to everyday life. Participants in the pilot of the Ageing Well Program highlighted that those aspects of the Program, such as the focus on adding value through targeting multiple aspects of ageing, as well as developing strategies to successfully learn, apply, and translate new knowledge into their everyday lives, were beneficial and supported engagement. However, future programs would benefit from the inclusion of clear and coherent written material to provide an aide in remembering the strategies and new information learnt during the Program. Findings support the importance and value of engaging with older people to assist with the development of community-based programs that are authentically designed to align with the expectations of older people, through a process of quality improvement.

SuperAgers and centenarians, dynamics of healthy ageing with cognitive resilience

Graceful healthy ageing and extended longevity is the most desired goal for human race. The process of ageing is inevitable and has a profound impact on the gradual deterioration of our physiology and health since it triggers the onset of many chronic conditions like dementia, osteoporosis, diabetes, arthritis, cancer, and cardiovascular disease. However, some people who lived/live more than 100 years called ‘Centenarians” and how do they achieve their extended lifespans are not completely understood. Studying these unknown factors of longevity is important not only to establish a longer human lifespan but also to manage and treat people with shortened lifespans suffering from age-related morbidities. Furthermore, older adults who maintain strong cognitive function are referred to as "SuperAgers" and may be resistant to risk factors linked to cognitive decline. Investigating the mechanisms underlying their cognitive resilience may contribute to the development of therapeutic strategies that support the preservation of cognitive function as people age. The key to a long, physically, and cognitively healthy life has been a mystery to scientists for ages. Developments in the medical sciences helps us to a better understanding of human physiological function and greater access to medical care has led us to an increase in life expectancy. Moreover, inheriting favorable genetic traits and adopting a healthy lifestyle play pivotal roles in promoting longer and healthier lives. Engaging in regular physical activity, maintaining a balanced diet, and avoiding harmful habits such as smoking contribute to overall well-being. The synergy between positive lifestyle choices, access to education, socio-economic factors, environmental determinants and genetic supremacy enhances the potential for a longer and healthier life. Our article aims to examine the factors associated with healthy ageing, particularly focusing on cognitive health in centenarians. We will also be discussing different aspects of ageing including genomic instability, metabolic burden, oxidative stress and inflammation, mitochondrial dysfunction, cellular senescence, immunosenescence, and sarcopenia.

Epigenetic age oscillates during the day.

Since their introduction, epigenetic clocks have been extensively used in aging, human disease, and rejuvenation studies. In this article, we report an intriguing pattern: epigenetic age predictions display a 24-h periodicity. We tested a circadian blood sample collection using 17 epigenetic clocks addressing different aspects of aging. Thirteen clocks exhibited significant oscillations with the youngest and oldest age estimates around midnight and noon, respectively. In addition, daily oscillations were consistent with the changes of epigenetic age across different times of day observed in an independant populational dataset. While these oscillations can in part be attributed to variations in white blood cell type composition, cell count correction methods might not fully resolve the issue. Furthermore, some epigenetic clocks exhibited 24-h periodicity even in the purified fraction of neutrophils pointing at plausible contributions of intracellular epigenomic oscillations. Evidence for circadian variation in epigenetic clocks emphasizes the importance of the time-of-day for obtaining accurate estimates of epigenetic age.

Leisure engagement in older age is related to objective and subjective experiences of aging

Leisure engagement has potential to slow health and functional decline in older age. However, the benefits of different leisure domains for different aspects of aging remains unclear. In 8771 older adults from the Health and Retirement Study (a longitudinal panel study), we measured engagement in physical, creative, cognitive, and community activities. Outcome-wide analyses used 23 aging experiences across seven domains eight years later (daily functioning, physical fitness, long-term physical health problems, heart health, weight, sleep, subjective perceptions of health). Physical activity was related to more positive experiences in all domains but heart health eight years later. Creative engagement was positively related to aging experiences in four domains longitudinally. Cognitive and community engagement were less consistently related to aging experiences. Physical and creative activities may influence important aging metrics, reducing age-related decline and keeping older adults functionally independent for longer, potentially limiting increasing healthcare costs.

Epigenetic and Metabolomic Biomarkers for Biological Age: A Comparative Analysis of Mortality and Frailty Risk.

Biological age captures a person's age-related risk of unfavorable outcomes using biophysiological information. Multivariate biological age measures include frailty scores and molecular biomarkers. These measures are often studied in isolation, but here we present a large-scale study comparing them. In 2 prospective cohorts (n = 3 222), we compared epigenetic (DNAm Horvath, DNAm Hannum, DNAm Lin, DNAm epiTOC, DNAm PhenoAge, DNAm DunedinPoAm, DNAm GrimAge, and DNAm Zhang) and metabolomic-based (MetaboAge and MetaboHealth) biomarkers in reflection of biological age, as represented by 5 frailty measures and overall mortality. Biomarkers trained on outcomes with biophysiological and/or mortality information outperformed age-trained biomarkers in frailty reflection and mortality prediction. DNAm GrimAge and MetaboHealth, trained on mortality, showed the strongest association with these outcomes. The associations of DNAm GrimAge and MetaboHealth with frailty and mortality were independent of each other and of the frailty score mimicking clinical geriatric assessment. Epigenetic, metabolomic, and clinical biological age markers seem to capture different aspects of aging. These findings suggest that mortality-trained molecular markers may provide novel phenotype reflecting biological age and strengthen current clinical geriatric health and well-being assessment.

Different Aspects of Aging in Migraine.

Migraine is a common neurological disease displaying an unusual dependence on age. For most patients, the peak intensity of migraine headaches occurs in 20s and lasts until 40s, but then headache attacks become less intense, occur less frequently and the disease is more responsive to therapy. This relationship is valid in both females and males, although the prevalence of migraine in the former is 2-4 times greater than the latter. Recent concepts present migraine not only as a pathological event, but rather as a part of evolutionary adaptive response to protect organism against consequences of stress-induced brain energy deficit. However, these concepts do not fully explain that unusual dependence of migraine prevalence on age. Many aspects of aging, both molecular/cellular and social/cognitive, are interwound in migraine pathogenesis, but they neither explain why only some persons are affected by migraine, nor suggest any causal relationship. In this narrative/hypothesis review we present information on associations of migraine with chronological aging, brain aging, cellular senescence, stem cell exhaustion as well as social, cognitive, epigenetic, and metabolic aging. We also underline the role of oxidative stress in these associations. We hypothesize that migraine affects only individuals who have inborn, genetic/epigenetic, or acquired (traumas, shocks or complexes) migraine predispositions. These predispositions weakly depend on age and affected individuals are more prone to migraine triggers than others. Although the triggers can be related to many aspects of aging, social aging may play a particularly important role as the prevalence of its associated stress has a similar age-dependence as the prevalence of migraine. Moreover, social aging was shown to be associated with oxidative stress, important in many aspects of aging. In perspective, molecular mechanisms underlying social aging should be further explored and related to migraine with a closer association with migraine predisposition and difference in prevalence by sex.

Epigenetic clocks in relapse after a first episode of schizophrenia

The main objective of the present study was to investigate the association between several epigenetic clocks, covering different aspects of aging, with schizophrenia relapse evaluated over a 3-year follow-up period in a cohort of ninety-one first-episode schizophrenia patients. Genome-wide DNA methylation was profiled and four epigenetic clocks, including epigenetic clocks of chronological age, mortality and telomere length were calculated. Patients that relapsed during the follow-up showed epigenetic acceleration of the telomere length clock (p = 0.030). Shorter telomere length was associated with cognitive performance (working memory, r = 0.31 p = 0.015; verbal fluency, r = 0.28 p = 0.028), but no direct effect of cognitive function or symptom severity on relapse was detected. The results of the present study suggest that epigenetic age acceleration could be involved in the clinical course of schizophrenia and could be a useful marker of relapse when measured in remission stages.

Adopting a "Compound" Exposome Approach in Environmental Aging Biomarker Research: A Call to Action for Advancing Racial Health Equity.

Background:In June 2020, the National Academies of Sciences, Engineering, and Medicine hosted a virtual workshop focused on integrating the science of aging and environmental health research. The concurrent COVID-19 pandemic and national attention on racism exposed shortcomings in the environmental research field’s conceptualization and methodological use of race, which have subsequently hindered the ability of research to address racial health disparities. By the workshop’s conclusion, the authors deduced that the utility of environmental aging biomarkers—aging biomarkers shown to be specifically influenced by environmental exposures—would be greatly diminished if these biomarkers are developed absent of considerations of broader societal factors—like structural racism—that impinge on racial health equity.Objectives:The authors reached a post-workshop consensus recommendation: To advance racial health equity, a “compound” exposome approach should be widely adopted in environmental aging biomarker research. We present this recommendation here.Discussion:The authors believe that without explicit considerations of racial health equity, people in most need of the benefits afforded by a better understanding of the relationships between exposures and aging will be the least likely to receive them because biomarkers may not encompass cumulative impacts from their unique social and environmental stressors. Employing an exposome approach that allows for more comprehensive exposure–disease pathway characterization across broad domains, including the social exposome and neighborhood factors, is the first step. Exposome-centered study designs must then be supported with efforts aimed at increasing the recruitment and retention of racially diverse study populations and researchers and further “compounded” with strategies directed at improving the use and interpretation of race throughout the publication and dissemination process. This compound exposome approach maximizes the ability of our science to identify environmental aging biomarkers that explicate racial disparities in health and best positions the environmental research community to contribute to the elimination of racial health disparities. https://doi.org/10.1289/EHP8392

Proteomic and transcriptomic profiling reveal different aspects of aging in the kidney.

Little is known about the molecular changes that take place in the kidney during the aging process. In order to better understand these changes, we measured mRNA and protein levels in genetically diverse mice at different ages. We observed distinctive change in mRNA and protein levels as a function of age. Changes in both mRNA and protein are associated with increased immune infiltration and decreases in mitochondrial function. Proteins show a greater extent of change and reveal changes in a wide array of biological processes including unique, organ-specific features of aging in kidney. Most importantly, we observed functionally important age-related changes in protein that occur in the absence of corresponding changes in mRNA. Our findings suggest that mRNA profiling alone provides an incomplete picture of molecular aging in the kidney and that examination of changes in proteins is essential to understand aging processes that are not transcriptionally regulated.

Study of Longitudinal Aging in Mice: Presentation of Experimental Techniques.

Aging is associated with functional and metabolic decline and is a risk factor for all noncommunicable diseases. Even though mice are routinely used for modeling human aging and aging-related conditions, no comprehensive assessment to date has been conducted on normative mouse aging. To address this gap, the Study of Longitudinal Aging in Mice (SLAM) was designed and implemented by the National Institute on Aging (NIA/NIH) as the mouse counterpart to the Baltimore Longitudinal Study of Aging (BLSA). In this manuscript, we describe the premise, study design, methodologies, and technologies currently employed in SLAM. We also discuss current and future study directions. In this large population mouse study, inbred C57BL/6J and outbred UM-HET3 mice of both sexes are longitudinally evaluated for functional, phenotypic, and biological health, and collection of biospecimens is conducted throughout their life span. Within the longitudinal cohorts, a cross-sectional arm of the study has also been implemented for the well-controlled collection of tissues to generate a biorepository. SLAM and studies stemming from SLAM seek to identify and characterize phenotypic and biological predictors of mouse aging and age-associated conditions, examine the degrees of functional and biomolecular variability that occur within inbred and genetically heterogeneous mouse populations with age, and assess whether these changes are consistent with alterations observed in human aging in BLSA. The findings from these studies will be critical for evaluating the utility of mouse models for studying different aspects of aging, both in terms of interpreting prior findings and designing and implementing future studies.

Data mining of human plasma proteins generates a multitude of highly predictive aging clocks that reflect different aspects of aging.

ABSTRACTWe previously identified 529 proteins that had been reported by multiple different studies to change their expression level with age in human plasma. In the present study, we measured the q‐value and age coefficient of these proteins in a plasma proteomic dataset derived from 4263 individuals. A bioinformatics enrichment analysis of proteins that significantly trend toward increased expression with age strongly implicated diverse inflammatory processes. A literature search revealed that at least 64 of these 529 proteins are capable of regulating life span in an animal model. Nine of these proteins (AKT2, GDF11, GDF15, GHR, NAMPT, PAPPA, PLAU, PTEN, and SHC1) significantly extend life span when manipulated in mice or fish. By performing machine‐learning modeling in a plasma proteomic dataset derived from 3301 individuals, we discover an ultra‐predictive aging clock comprised of 491 protein entries. The Pearson correlation for this clock was 0.98 in the learning set and 0.96 in the test set while the median absolute error was 1.84 years in the learning set and 2.44 years in the test set. Using this clock, we demonstrate that aerobic‐exercised trained individuals have a younger predicted age than physically sedentary subjects. By testing clocks associated with 1565 different Reactome pathways, we also show that proteins associated with signal transduction or the immune system are especially capable of predicting human age. We additionally generate a multitude of age predictors that reflect different aspects of aging. For example, a clock comprised of proteins that regulate life span in animal models accurately predicts age.

Interactions Between Different Age-Related Factors Affecting Balance Control in Walking.

Maintaining balance during walking is a continuous sensorimotor control problem. Throughout the movement, the central nervous system has to collect sensory data about the current state of the body in space, use this information to detect possible threats to balance and adapt the movement pattern to ensure stability. Failure of this sensorimotor loop can lead to dire consequences in the form of falls, injury and death. Such failures tend to become more prevalent as people get older. While research has established a number of factors associated with higher risk of falls, we know relatively little about age-related changes of the underlying sensorimotor control loop and how such changes are related to empirically established risk factors. This paper approaches the problem of age-related fall risk from a neural control perspective. We begin by summarizing recent empirical findings about the neural control laws mapping sensory input to motor output for balance control during walking. These findings were established in young, neurotypical study populations and establish a baseline of sensorimotor control of balance. We then review correlates for deteriorating balance control in older adults, of muscle weakness, slow walking, cognitive decline, and increased visual dependency. While empirical associations between these factors and fall risk have been established reasonably well, we know relatively little about the underlying causal relationships. Establishing such causal relationships is hard, because the different factors all co-vary with age and are difficult to isolate empirically. One option to analyze the role of an individual factor for balance control is to use computational models of walking comprising all levels of the sensorimotor control loop. We introduce one such model that generates walking movement patterns from a short list of spinal reflex modules with limited supraspinal modulation for balance. We show how this model can be used to simulate empirical studies, and how comparison between the model and empirical results can indicate gaps in our current understanding of balance control. We also show how different aspects of aging can be added to this model to study their effect on balance control in isolation.

Influence of Sociodemographic, Behavioral and Other Health-Related Factors on Healthy Ageing Based on Three Operative Definitions

ObjectivesHealthy ageing (HA) is a key concept and highly desirable phenomenon in every ageing and already old societies. The aim of our study was to evaluate the influence of socio-economic conditions as well as life-style and other health-related factors on the WHO definition of HA.Design, Setting, ParticipantsThe study used cross-sectional data of the PolSenior Project — nationwide research evaluating different aspects of ageing in Poland — which included 4’653 respondents aged 65 years and over.MeasurementsData were collected by trained interviewers in respondents’ homes. Three definitions of HA including or not the participants’ chronic conditions were analyzed.ResultsThe prevalence of HA appeared as high as 17.6% if none or 1 chronic disease was present and 42.8% if no information about chronic diseases was taken into account. The association between known health predictors (age, marital status, education, income) and HA was observed. Moreover, HA appeared in relation with indicators of physical functioning and lifestyle. There was a strong concordance between HA and the fair self-rated health (OR = 1.87; 1.99, and 2.74 for the 1st, 2nd and 3rd definitions, respectively) and opposite relation with self-reported need for help (OR = 0.15; 0.15; and 0.13, respectively).ConclusionsThe HA definition based on no functional activity limitations, no cognitive impairment, no depressive symptoms, no more than one disease and being socially active seems to be a useful approach of HA..

Capacitação, conhecimentos e crenças de médicos da Atenção Primária à Saúde relacionados ao envelhecimento

O aumento da população idosa, com os complexos problemas de saúde que a envolvem, evidencia a necessidade do uso da Atenção Primária à Saúde (APS), que deve ser a porta de entrada para a atenção à saúde dos idosos. Espera-se que a APS exerça ações curativas e, principalmente, de prevenção e promoção à saúde para este grupo etário. O objetivo deste estudo foi avaliar, em 49 médicos que atuam na APS de Anápolis, estado de Goiás, a formação profissional na área do envelhecimento, os conhecimentos básicos sobre a velhice e as crenças relacionadas aos idosos. Foram aplicados os seguintes questionários: formação acadêmica na área do envelhecimento; Questionário Palmore-Neri-Cachioni, a fim de avaliar os conhecimentos básicos sobre a velhice; e Escala de Neri, para verificar as crenças relacionadas aos idosos. Os médicos mostraram carecer de formação acadêmica e conhecimentos básicos na área gerontológica. Entre eles, 22,4% deles não cursaram a disciplina Geriatria e Gerontologia na graduação, 71,4% não tinham qualquer tipo de especialização, 91,8% não fizeram residência médica. Nos últimos cinco anos, somente 38,8% participaram de cursos de Geriatria e Gerontologia, 10,2% fizeram pesquisa na área, e 59,2% leram algum artigo sobre envelhecimento. Na avaliação dos conhecimentos básicos sobre a velhice, os maiores números de acertos, 91,8% e 83,7%, surgiram nas duas questões que tratam de aspectos físicos do envelhecimento. A questão que recebeu menor número de acertos (6,1%) aborda o aspecto social do envelhecimento; e as duas questões que tratam de aspectos psicológicos tiveram menos de 20% de acertos. Quanto às crenças relacionadas à velhice, a tendência geral das respostas foi negativa. O domínio com avaliação mais positiva foi Agência e o com avaliação mais negativa foi Relacionamento Social. O item com crença mais positiva foi o relacionado à sabedoria. Concluiu-se que é necessária educação continuada para os médicos que atuam na APS, focada nos diferentes aspectos do envelhecimento, incluindo os psicossociais, assim como a adoção de crenças positivas relacionadas aos idosos.

Abstract P3-05-01: Age-related methylation signals of breast cancer risk in blood

Abstract BACKGROUND: Age is the biggest risk factor for developing breast cancer, which suggests that the biological aging process is a direct driver of cancer etiology. In all normal tissues, DNA methylation status changes systematically with age and is believed to mediate the biological consequences of aging. DNA methylation patterns, commonly referred to as 'Epigenetic Clocks', can be used as measures of aging. However, the chronologic and epigenetic ages can have subtle differences in different individuals. We hypothesize that accelerated epigenetic aging (i.e. DNA methylation indicating an older age than the chronologic age of the individual) is a risk factor for breast cancer development. METHODS: We used DNA methylation data from blood samples and clinical data from n=2,107 participants in the Women's Health Initiative (WHI) and tested the association between breast cancer risk and two of the most commonly used epigenetic clocks by Horvath (based on 353 CpGs) and Hannum et al. (based on 71 CpGs). DNA methylation in whole blood was measured using the Illumina HumanMethylation450 BeadChip. We used Cox proportional hazard models to assess the association between two epigenetic age predictors (calculated using the algorithms by Horvath and Hannum et al.) and subsequent risk of breast cancer. The model was adjusted for several breast cancer risk factors including: chronologic age at the time of blood sampling, observational vs. clinical trial, clinical trial arm, race/ethnicity, education, BMI, waist-hip ratio, smoking, alcohol, age at menopause, age at menarche, number of pregnancies, age at first birth, previous mastectomy, months breastfed, and cell count estimates. Family history data and BRCA mutation status was incomplete in the WHI and therefore could not be included in our analysis. RESULTS: Increased epigenetic age determined by the Horvath clock relative to chronological age was associated with increased future incidence of invasive breast cancer, even after adjusting for known risk factors (HR=1.04, P=0.03). Utilizing the Hannum clock, we found no significant association between epigenetic age and breast cancer risk (HR=1.01, P=0.568). When we included both age predictors as independent variables in a single model, the strength of the association between the Horvath epigenetic age and breast cancer risk increased (Horvath HR=1.09, P=6.3e-5; Hannum HR=0.95, p=0.077), such that every one year increase in epigenetic age relative to chronological age was associated with a 9% increased risk of future breast cancer. These results suggest that the aging signal in the Horvath clock that is unique from that captured by Hannum is what drives the specific association with breast cancer. CONCLUSIONS: Our results support the hypothesis that “accelerated” epigenetic aging measured in the blood increases breast cancer risk. We also demonstrate that the two epigenetic clocks capture different aspects of aging, only some of which have implications for breast cancer risk. Epigenetic clocks may assist in targeting breast cancer screening to higher risk populations in the future, and understanding the biological mechanisms that are altered by the epigenetic changes may lead to new risk reduction strategies. Citation Format: Hofstatter EW, Levine M, Hatzis C, Pusztai L. Age-related methylation signals of breast cancer risk in blood [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-05-01.

Epigenetic Clock and Relative Telomere Length Represent Largely Different Aspects of Aging in the Berlin Aging Study II (BASE-II).

DNA methylation age (DNAm age; "epigenetic clock") has recently been described as highly correlated with chronological age. Several studies suggest that DNAm age reflects, at least in part, biological age. Here, we adapted a recently published methylation-sensitive single nucleotide primer extension method for epigenetic age estimation and calculated the DNAm age based on only seven cytosine-phosphate-guanine sites in 1,895 DNA samples of the Berlin Aging Study II. In a second step, we explored the relationship between this new potential measure of biological age with an established marker of biological age, relative leukocyte telomere length (rLTL), in the same cohort. Our results showed a positive and significant correlation between DNAm age estimation and chronological age (N = 1,895, Rs2 = .47), which persisted after adjustment for covariates (sex, leukocyte distribution, alcohol and smoking). We found a significant but weak negative association between DNAm age acceleration and rLTL in linear regression analysis adjusted for age, sex, alcohol and smoking (β = -0.002, p = .007). Therefore, DNAm age appears to be a promising biomarker in the analysis of phenotypes of aging, which are not (only) related to pathways associated with mitotic age as measured by rLTL.

Leucocyte telomere length is no molecular marker of physical frailty in late-life depression.

Although average life-expectancy is still increasing worldwide, ageing processes markedly differ between individuals, which has stimulated the search for biomarkers of biological ageing. Firstly, to explore the cross-sectional and longitudinal association between leucocyte telomere length (LTL) as molecular marker of ageing and the physical frailty phenotype (PFP) as a clinical marker of ageing and secondly, to examine whether these associations are moderated by the presence of a depressive disorder, as depression can be considered a condition of accelerated ageing. Among 378 depressed older patients (according to DSM-IV criteria) and 132 non-depressed older persons participating in the Netherlands Study of Depression in Older persons, we have assessed the physical frailty phenotype and LTL. The PFP was defined according to Fried's criteria and its components were reassessed at two-year follow-up. LTL was neither associated with the PFP at baseline by Spearman rank correlation tests, nor did it predict change in frailty parameters over a two-year follow-up using regression analyses adjusted for potential confounders. LTL is not associated with frailty; neither in non-depressed nor in depressed older persons. As LTL and physical frailty appear to represent different aspects of ageing, they may complement each other in future studies.

Age-related differences in associative memory: Empirical evidence and theoretical perspectives.

Systematic research and anecdotal evidence both indicate declines in episodic memory in older adults in good health without dementia-related disorders. Several hypotheses have been proposed to explain these age-related changes in episodic memory, some of which attribute such declines to a deterioration in associative memory. The current special issue of Psychology and Aging on Age-Related Differences in Associative Memory includes 16 articles by top researchers in the area of memory and aging. Their contributions provide a wealth of empirical work that addresses different aspects of aging and associative memory, including different mediators and predictors of age-related declines in binding and associative memory, cognitive, noncognitive, genetic, and neuro-related ones. The contributions also address the processing phases where these declines manifest themselves and look at ways to ameliorate these age-related declines. Furthermore, the contributions in this issue draw on different theoretical perspectives to explain age-related changes in associative memory and provide a wealth of varying methodologies to assess older and younger adults' performance. Finally, although most of the studies focus on normative/healthy aging, some of them contain insights that are potentially applicable to disorders and pathologies. (PsycINFO Database Record

The role of sodium hydrosulfide in attenuating the aging process via PI3K/AKT and CaMKKβ/AMPK pathways

Age-related dysfunction of the central auditory system, known as central presbycusis, is characterized by defects in speech perception and sound localization. It is important to determine the pathogenesis of central presbycusis in order to explore a feasible and effective intervention method. Recent work has provided fascinating insight into the beneficial function of H2S on oxidative stress and stress-related disease. In this study, we investigated the pathogenesis of central presbycusis and tried to explore the mechanism of H2S action on different aspects of aging by utilizing a mimetic aging rat and senescent cellular model. Our results indicate that NaHS decreased oxidative stress and apoptosis levels in an aging model via CaMKKβ and PI3K/AKT signaling pathways. Moreover, we found that NaHS restored the decreased activity of antioxidants such as GSH, SOD and CAT in the aging model in vivo and in vitro by regulating CaMKKβ and PI3K/AKT. Mitochondria function was preserved by NaHS, as indicated by the following: DNA POLG and OGG-1, the base excision repair enzymes in mitochondrial, were upregulated; OXPHOS activity was downregulated; mitochondrial membrane potential was restored; ATP production was increased; and mtDNA damage, indicated by the common deletion (CD), declined. These effects were also achieved by activating CaMKKβ/AMPK and PI3K/AKT signaling pathways. Lastly, protein homeostasis, indicated by HSP90 alpha, was strengthened by NaHS via CaMKKβ and PI3K/AKT. Our findings demonstrate that the ability to resist oxidative stress and mitochondria function are both decreased as aging developed; however, NaHS, a novel free radical scavenger and mitochondrial protective agent, precludes the process of oxidative damage by activating CaMKKβ and PI3K/AKT. This study might provide a therapeutic target for aging and age-related disease.