Physiological and Molecular Mechanisms Associated with Potato Tuber Dormancy.

Tuber dormancy is an important physiological trait that impacts postharvest storage and end use qualities of potatoes. Overall, dormancy regulation of potato tuber is a complex process driven by genetic as well as environmental factors. Elucidation of the molecular and physiological mechanisms that influence different dormancy stages of tuber has wider potato breeding and industry relevant implications. Therefore, the primary objective of this review is to present the current knowledge on the diversity in tuber dormancy traits among wild relatives of potatoes and discuss how genetic and epigenetic factors contribute to the tuber dormancy. Advancements in understanding of key physiological mechanisms involved in tuber dormancy regulations, such as apical dominance, phytohormone metabolism, and oxidative stress responses were also discussed. This review highlights the impacts of common sprout suppressors on the molecular and physiological mechanisms associated with tuber dormancy and other storage qualities. Collectively, the literature suggests that significant changes in expressions of genes associated with cell cycle, phytohormone metabolism, and oxidative stress response influence initiation, maintenance, and termination of dormancy in potato tubers. Commercial sprout suppressors mainly alter the expressions of genes associated with cell cycle and stress responses and suppress sprout growth rather than prolonging the tuber dormancy.

Hutchinson-Gilford Progeria Syndrome: Cardiovascular Pathologies and Potential Therapies.

Hutchinson-Gilford progeria syndrome (HGPS) is an ultrarare and fatal disease with features of premature aging and cardiovascular diseases (atherosclerosis, myocardial infarction, and stroke). Several landmark studies in 2018-2019 have revealed novel mechanisms underlying cardiovascular pathologies in HGPS, and implicate future potential therapies for HGPS, and possibly physiological aging.

Predictors of healthy physiological aging across generations in a 30-year population-based cohort study: the Doetinchem Cohort Study.

BACKGROUND: Predicting healthy physiological aging is of major interest within public health research. However, longitudinal studies into predictors of healthy physiological aging that include numerous exposures from different domains (i.e. the exposome) are scarce. Our aim is to identify the most important exposome-related predictors of healthy physiological aging over the life course and across generations. METHODS: Data were used from 2815 participants from four generations (generation 1960s/1950s/1940s/1930s aged respectively 20-29/30-39/40-49/50-59 years old at baseline, wave 1) of the Doetinchem Cohort Study who were measured every 5 years for 30 years. The Healthy Aging Index, a physiological aging index consisting of blood pressure, glucose, creatinine, lung function, and cognitive functioning, was measured at age 46-85 years (wave 6). The average exposure and trend of exposure over time of demographic, lifestyle, environmental, and biological exposures were included, resulting in 86 exposures. Random forest was used to identify important predictors. RESULTS: The most important predictors of healthy physiological aging were overweight-related (BMI, waist circumference, waist/hip ratio) and cholesterol-related (using cholesterol lowering medication, HDL and total cholesterol) measures. Diet and educational level also ranked in the top of important exposures. No substantial differences were observed in the predictors of healthy physiological aging across generations. The final prediction model's performance was modest with an R2 of 17%. CONCLUSIONS: Taken together, our findings suggest that longitudinal cardiometabolic exposures (i.e. overweight- and cholesterol-related measures) are most important in predicting healthy physiological aging. This finding was similar across generations. More work is needed to confirm our findings in other study populations.

[Gender differences in the volume of brain structures in the aspect of physiological aging.]

The aim of the work was to clarify the gender, age and variable differences in the structure of brain structures in healthy volunteers in connection with the task of distinguishing between physiological aging and pathological processes of the brain. The study methods included performing structural MRI of the brain in 131 conditionally healthy volunteers aged 20 to 70 years (72 of them were women and 59 men). Using the method of MR voxel-based morphometry, the total volume of the brain as a whole, as well as its segmented parts, was measured, followed by a comparison of the data obtained in age subgroups and between the sexes. The data obtained in the course of the study indicate that the right and left thalamuses, the left caudate nucleus, the right shell, the left pale ball, and both hippocampus undergo the greatest reduction in size after 60 years. The greatest changes in the hippocampus are the volumes of CA3 Brodman fields. It is established that the process of «physiological aging¼ of the brain.

The Healthy Aging Index analyzed over 15 years in the general population: The Doetinchem Cohort Study.

The Healthy Aging Index (HAI), an index of physiological aging, has been demonstrated to predicts mortality, morbidity and disability. We studied the longitudinal development of the HAI to identify aging trajectories and evaluated the role of baseline sociodemographic characteristics and lifestyle factors of the trajectories. Four measurements with intervals of 5 years were included from the Doetinchem Cohort Study. The HAI reflects levels of systolic blood pressure, non-fasting plasma glucose levels, global cognitive functioning, plasma creatinine levels and lung functioning. The HAI score ranges from 0 to 10: higher scores indicate a better health profile. Latent class mixture modelling was used to model within-person change and to identify aging trajectories. Area under the curve was calculated per trajectory to estimate total healthy years. In total, 2324 women and 2013 men were included. One HAI trajectory was identified for women, and two trajectories for men, labelled 'gradual' aging (76%) and 'early' aging (24%). Men who were medium/high educated, below 36 years at baseline, complied with guidelines on physical activity and were not obese in any round were associated with increased odds to 'gradual' aging of 1.46 (CI: 1.18-1.81), 1.93 (CI: 1.42-2.62), 1.26 (1.02-1.57) and 1.76 (1.32-2.35), respectively. Between 30 and 70 years of age, men in the 'early' aging trajectory had the least healthy years (29.6 years), followed by women (30.1 years), and 'gradual' aging men (34.7 years). This study emphasizes that 'physiological aging' is not only an issue of older ages. Between 30 and 70 years of age, 'early' aging men and women had approximately five healthy years less compared to 'gradual' aging men. Lifestyle factors (e.g. nutrition and physical activity) seem to play an important role in optimal aging.

[Researches on testicular aging: Status quo and prospects].

Testis is the male gonad with the main functions of secreting androgens and producing sperm. Testicular aging can induce sexual and reproductive dysfunctions and a series of systemic symptoms, which not only seriously affect the life quality of elderly and middle-aged men but are also closely related to the development and progression of chronic diseases, such as vascular and metabolic disorders. This review focuses on the concept, clinical manifestations, pathogenesis, evaluation methods and intervention strategies of testicular aging, as well as the prospects for its future research directions, aiming to help clinicians gain a deeper insight into and attach more importance to this condition, so as to improve its prevention and treatment.

[Normal sensory aging]. / Le vieillissement sensoriel normal.

Normal aging can be defined as the result of the effects of genetic and environmental factors to which subjects are exposed throughout their lives. This process is slow and progressive and must be distinguished from disease. All organs are subject to aging in a physiological way.

Structure-function multi-scale connectomics reveals a major role of the fronto-striato-thalamic circuit in brain aging.

Physiological aging affects brain structure and function impacting morphology, connectivity, and performance. However, whether some brain connectivity metrics might reflect the age of an individual is still unclear. Here, we collected brain images from healthy participants (N = 155) ranging from 10 to 80 years to build functional (resting state) and structural (tractography) connectivity matrices, both data sets combined to obtain different connectivity features. We then calculated the brain connectome age-an age estimator resulting from a multi-scale methodology applied to the structure-function connectome, and compared it to the chronological age (ChA). Our results were twofold. First, we found that aging widely affects the connectivity of multiple structures, such as anterior cingulate and medial prefrontal cortices, basal ganglia, thalamus, insula, cingulum, hippocampus, parahippocampus, occipital cortex, fusiform, precuneus, and temporal pole. Second, we found that the connectivity between basal ganglia and thalamus to frontal areas, also known as the fronto-striato-thalamic (FST) circuit, makes the major contribution to age estimation. In conclusion, our results highlight the key role played by the FST circuit in the process of healthy aging. Notably, the same methodology can be generally applied to identify the structural-functional connectivity patterns correlating to other biomarkers than ChA.

[The battery of tests for behavioral phenotyping of aging animals in the experiment].

The purpose of the study was to develop a battery of tests to study social and cognitive impairments for behavioral phenotyping of aging experimental animals with physiological neurodegeneration. Object of the study were outbred CD1 mice in the following groups: 1st group - 12-month old male mice (physiological aging); 2nd group - 2-month old male mice (control group). Social recognition test, elevated plus maze test (EPM), open field test, light-dark box test, and Fear conditioning protocol were used to estimate the neurological status of experimental animals. We found that aging male mice in a contrast to young ones have demonstrated lower social interest to female mice in the social recognition task. EPM and light-dark box tests showed increased level of anxiety in the group of aged mice comparing to the control group. Fear conditioning protocol revealed impairment of associative learning and memory in the group of aged mice, particularly, fear memory consolidation was dramatically suppressed. Analysis of behavioral factors, social interactions and anxiety level in the experimental mice has confirmed age-related neurodegeneration in the 1st group. We found that the most informative approach to identifying neurological impairments in aging mice (social interaction deficit, limitation of interests, increased level of anxiety) should be based on the open field test light-dark box test, and Fear conditioning protocol. Such combination allows obtaining new data on behavioral alterations in the age-associated of neurodegeneration and to develop novel therapeutic strategies for the treatment of age-related brain pathology.

The microarchitecture and chemical composition of the femur neck of senescent female rats after different physical training protocols.

A sedentary lifestyle, coupled with a decrease in estrogen, impairs bone homeostasis, favoring to the development of osteopenia and osteoporosis, both recognized as risk factors for fractures. Here, we investigated the quality of the femur, particularly the femur neck region, and the ambulation performance of senescent rats subjected to three different physical training protocols during the periestropause period. Forty-eight female rats, 18 months of age, were subjected to a 120-day training period, three times a week. The rats were distributed into four groups: aerobic training (AT), strength training (ST), concurrent training (CT), or no training (NT). After the experimental period, at 21 months of age, ambulation performance and femur were analyzed using microtomography, Raman stereology, densitometry, and mechanical strength tests. The results demonstrated greater remodeling activity and improvement in resistance and bone microarchitecture in the femur neck of senescent female rats after undergoing physical training. Our verified higher intensities of bands related to collagen, phosphate, amide III, and amide I. Furthermore, the analysis of the secondary collagen structures indicated alterations in the collagen network due to the exercise, resulting in increased bone strength. Both AT and strength-based training proved beneficial, with AT showing greater adaptations in bone density and stiffness in the femur, while strength-based training greater adaptations in trabecular and cortical structure. These insights contribute to the understanding of the potential interventions for preventing osteopenia and osteoporosis, which are critical risk factors for fractures.

Comparing the associations between muscle strength, walking speed, and mortality in community-dwelling older adults of two birth cohorts born 28 years apart.

Reduced age-specific mortality and increased muscle strength and walking speed of current older adults may have altered the relationships between these factors as more people may be above the reserve capacity threshold. We compared the cross-sectional associations between muscle strength and walking speed, and the associations of muscle strength and walking speed with five-year mortality between two population-based cohorts of 75- and 80-year-old people born 28 years apart. Maximal isometric grip and knee extension strength and walking speed were measured in 2017-2018 (n = 726). Mortality was ascertained from registers. The associations were compared with data of same-aged people studied in 1989-1990 with identical protocols (n = 500). The knee extension strength-walking speed relationship showed plateauing at higher strength levels among the later-born men, whereas the earlier-born men and women of both cohorts with lower strength levels were on the linear part of the curve. In the later-born women with lower five-year mortality rate (1.16 vs. 5.88 per 100 person-years), the association between grip strength and mortality was markedly different from the earlier cohort (HR 1.13 [95% CI 0.47-2.70] vs. 0.57 [0.37-0.86]). For knee extension strength and walking speed, the mortality hazards were similar between the cohorts, although statistically non-significant in the later-born women. In men, the later-born cohort showed similar associations as observed in the earlier-born cohort despite having lower mortality rate (2.93 vs. 6.44). Current older adults have more functional reserve that will likely help them to maintain walking ability for longer while also contributing to better survival.

Fluid biomarkers unveil signatures of pathological aging.

Aging is a multifaceted and highly varied process in the brain. Identifying aging biomarkers is one means of distinguishing pathological from physiological aging. The aim of this narrative review is to focus on two new developments in the field of fluid biomarkers and draw attention to this excellent tool for the early detection of potential brain pathologies that delay, alter, or enable physiological aging to become pathological. Pathological aging can lower the threshold for the development of specific diseases such as late-onset epilepsy. Fluid biomarkers can reveal pathological levels at an early stage and thus indicate disease processes in the brain that begin before symptoms develop; they thus differ from physiological aging.

Amniotic stem cells as a source of regenerative medicine to treat female infertility.

Impaired reproductive health is a worldwide problem that affects the psychological well-being of a society. Despite the technological developments to treat infertility, the global infertility rate is increasing significantly. Many infertility conditions are currently treated using various advanced clinical approaches such as intrauterine semination (IUI), in vitro fertilization (IVF), and intracytoplasmic injection (ICSI). Nonetheless, clinical management of some conditions such as dysfunctional endometrium, premature ovarian failure, and ovarian physiological aging still pose significant challenges. Stem cells based therapeutic strategies have a long-standing history to treat many infertility conditions, but ethical restrictions do not allow the broad-scale utilization of adult mesenchymal stromal/stem cells (MSCs). Easily accessible, placental derived or amniotic stem cells present an invaluable alternative source of non-immunogenic and non-tumorigenic stem cells that possess multilineage potential. Given these characteristics, placental or amniotic stem cells (ASCs) have been investigated for therapeutic purposes to address infertility in the last decade. This study aims to summarize the current standing and progress of human amniotic epithelial stem cells (hAECs), amniotic mesenchymal stem cells (hAMSCs), and amniotic fluid stem cells (hAFSCs) in the field of reproductive medicine. The therapeutic potential of these cells to restore or enhance normal ovarian function and pregnancy outcomes are highlighted in this study.

A metabolomic signature of decelerated physiological aging in human plasma.

The degenerative processes that occur during aging increase the risk of disease and impaired health. Meanwhile, interventions that target aging to promote healthy longevity are gaining interest, both academically and in the public. While nutritional and physical interventions exist, efficacy is often difficult to determine. It is therefore imperative that an aging score measuring the biological aging process is available to the wider public. However, simple, interpret, and accessible biological aging scores are lacking. Here, we developed PhysiAge, a physiological aging score based on five accessible parameters that have influence on or reflect the aging process: (1) average daily step count, (2) blood glucose, (3) systolic blood pressure, (4) sex, and (5) age. Here, we found that compared to calendar age alone, PhysiAge better predicts mortality, as well as established muscle aging markers such as decrease in NAD+ levels, increase in oxidative stress, and decline in physical functioning. In order to demonstrate the usefulness of PhysiAge in identifying relevant factors associated with decelerated aging, we calculated PhysiAges for a cohort of aged individuals and obtained mass spectrometry-based blood plasma metabolomic profiles for each individual. Here, we identified a metabolic signature of decelerated aging, which included components of the TCA cycle, including malate, citrate, and isocitrate. Higher abundance of these metabolites was associated with decelerated aging, in line with supplementation studies in model organisms. PhysiAge represents an accessible way for people to track and intervene in their aging trajectories, and identifies a metabolic signature of decelerated aging in human blood plasma, which can be further studied for its causal involvement in human aging.

Early Life Racial Discrimination, Racial Centrality, and Allostatic Load Among African American Older Adults.

BACKGROUND AND OBJECTIVES: Prior research documents accelerated physiological aging among African Americans due to their greater lifetime exposure to social and economic adversity. Yet, less is known about the mechanisms through which early life stressors, such as early life racial discrimination (ELRD), and later life psychosocial resources, such as racial centrality (i.e., importance of Black identity to one's sense of self), interact to shape allostatic load (AL) in adulthood. We evaluate the life course processes linking ELRD, adult racial centrality, and adult AL among older African Americans. RESEARCH DESIGN AND METHODS: Data from the Nashville Stress and Health Study included African Americans aged 50 and older (N = 260). Poisson regression models assessed the links between ELRD, adult centrality, and adult AL. Interactions determined whether ELRD conditions the centrality-AL association in adulthood. RESULTS: Adolescent ELRD conferred significantly higher levels of adult centrality and 32% increased risk of high adult AL. Greater adult centrality was linked to high adult AL, but the ELRD-adult AL association was not explained by centrality. However, ELRD and centrality interact to shape adult AL, such that racial centrality was protective against high adult AL for those who experienced racial discrimination as children or adolescents. DISCUSSION AND IMPLICATIONS: Findings highlight the multiple pathways through which racism-related stressors and psychosocial resources interact to shape physiological dysregulation in later life and underscore the health significance of racial identity for older African Americans. Clinicians and public health professionals should assess early life stressors and foster psychosocial resilience to promote healthy aging.

Sex- and Age-Related Physiological Profiles for Brachial, Vertebral, Carotid, and Femoral Arteries Blood Flow Velocity Parameters During Growth and Aging (4-76 Years): Comparison With Clinical Cut-Off Levels.

Ultrasound-derived blood flow velocity (BFV) levels [e.g., peak systolic velocity (PSV)], intrabeat indexes (e.g., resistive), and intersegment ratios [e.g., internal/common carotid artery (ICA/CCA) PSV ratio] are assessed to describe cardiovascular physiology and health status (e.g., disease severity evaluation and/or risk stratification). In this respect, fixed cut-off values (disregard of age or sex) have been proposed to define "significant" vascular disease from BFV-derived data (parameters). However, the use of single fixed cut-off values has limitations. Accurate use of BFV-derived parameters requires knowing their physiological age-related profiles and the expected values for a specific subject. To our knowledge, there are no studies that have characterized BFV profiles in large populations taking into account: (i) data from different age-stages (as a continuous) and transitions (childhood-adolescence-adulthood), (ii) complementary parameters, (iii) data from different arteries, and (iv) potential sex- and hemibody-related differences. Furthermore, (v) there is little information regarding normative data [reference intervals (RIs)] for BFV indexes. Aims: The aims of this study are the following: (a) to determine the need for age-, body side-, and sex-specific profiles for BFV levels and derived parameters (intrabeat indexes and intersegment ratios), and (b) to define RIs for BFV levels and parameters, obtained from CCA, ICA, external carotid, vertebral, femoral, and brachial arteries records. Methods: A total of 3,619 subjects (3-90 years) were included; 1,152 were healthy (without cardiovascular disease and atheroma plaques) and non-exposed to cardiovascular risk factors. BFV data were acquired. The agreement between left and right data was analyzed (Concordance correlation, Bland-Altman). Mean and SD equations and age-related profiles were obtained for BFV levels and parameters (regression methods; fractional polynomials). Results: Left and right body-side derived data were not always equivalent. The need for sex-specific RIs was dependent on the parameter and/or age considered. RIs were defined for each studied artery and parameter. Percentile curves were compared with recommended fixed cut-off points. The equations for sex, body-side, and age-specific BFV physiological profiles obtained in the large population (of children, adolescents, and adults) studied were included (spreadsheet formats), enabling to determine for a particular subject, the expected values and potential data deviations.

The Biology and Pathobiology of Glutamatergic, Cholinergic, and Dopaminergic Signaling in the Aging Brain.

The elderly population is growing worldwide, with important health and socioeconomic implications. Clinical and experimental studies on aging have uncovered numerous changes in the brain, such as decreased neurogenesis, increased synaptic defects, greater metabolic stress, and enhanced inflammation. These changes are associated with cognitive decline and neurobehavioral deficits. Although aging is not a disease, it is a significant risk factor for functional worsening, affective impairment, disease exaggeration, dementia, and general disease susceptibility. Conversely, life events related to mental stress and trauma can also lead to accelerated age-associated disorders and dementia. Here, we review human studies and studies on mice and rats, such as those modeling human neurodegenerative diseases, that have helped elucidate (1) the dynamics and mechanisms underlying the biological and pathological aging of the main projecting systems in the brain (glutamatergic, cholinergic, and dopaminergic) and (2) the effect of defective glutamatergic, cholinergic, and dopaminergic projection on disabilities associated with aging and neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. Detailed knowledge of the mechanisms of age-related diseases can be an important element in the development of effective ways of treatment. In this context, we briefly analyze which adverse changes associated with neurodegenerative diseases in the cholinergic, glutaminergic and dopaminergic systems could be targeted by therapeutic strategies developed as a result of our better understanding of these damaging mechanisms.

Predicting physiological aging rates from a range of quantitative traits using machine learning.

It is widely thought that individuals age at different rates. A method that measures "physiological age" or physiological aging rate independent of chronological age could therefore help elucidate mechanisms of aging and inform an individual's risk of morbidity and mortality. Here we present machine learning frameworks for inferring individual physiological age from a broad range of biochemical and physiological traits including blood phenotypes (e.g., high-density lipoprotein), cardiovascular functions (e.g., pulse wave velocity) and psychological traits (e.g., neuroticism) as main groups in two population cohorts SardiNIA (~6,100 participants) and InCHIANTI (~1,400 participants). The inferred physiological age was highly correlated with chronological age (R2 > 0.8). We further defined an individual's physiological aging rate (PAR) as the ratio of the predicted physiological age to the chronological age. Notably, PAR was a significant predictor of survival, indicating an effect of aging rate on mortality. Our trait-based PAR was correlated with DNA methylation-based epigenetic aging score (r = 0.6), suggesting that both scores capture a common aging process. PAR was also substantially heritable (h2~0.3), and a subsequent genome-wide association study of PAR identified significant associations with two genetic loci, one of which is implicated in telomerase activity. Our findings support PAR as a proxy for an underlying whole-body aging mechanism. PAR may thus be useful to evaluate the efficacy of treatments that target aging-related deficits and controllable epidemiological factors.

Cell and Cell-Free Therapies to Counteract Human Premature and Physiological Aging: MSCs Come to Light.

The progressive loss of the regenerative potential of tissues is one of the most obvious consequences of aging, driven by altered intercellular communication, cell senescence and niche-specific stem cell exhaustion, among other drivers. Mesenchymal tissues, such as bone, cartilage and fat, which originate from mesenchymal stem cell (MSC) differentiation, are especially affected by aging. Senescent MSCs show limited proliferative capacity and impairment in key defining features: their multipotent differentiation and secretory abilities, leading to diminished function and deleterious consequences for tissue homeostasis. In the past few years, several interventions to improve human healthspan by counteracting the cellular and molecular consequences of aging have moved closer to the clinic. Taking into account the MSC exhaustion occurring in aging, advanced therapies based on the potential use of young allogeneic MSCs and derivatives, such as extracellular vesicles (EVs), are gaining attention. Based on encouraging pre-clinical and clinical data, this review assesses the strong potential of MSC-based (cell and cell-free) therapies to counteract age-related consequences in both physiological and premature aging scenarios. We also discuss the mechanisms of action of these therapies and the possibility of enhancing their clinical potential by exposing MSCs to niche-relevant signals.

Impact of Chaperone-Mediated Autophagy in Brain Aging: Neurodegenerative Diseases and Glioblastoma.

Brain aging is characterized by a time-dependent decline of tissue integrity and function, and it is a major risk for neurodegenerative diseases and brain cancer. Chaperone-mediated autophagy (CMA) is a selective form of autophagy specialized in protein degradation, which is based on the individual translocation of a cargo protein through the lysosomal membrane. Regulation of processes such as proteostasis, cellular energetics, or immune system activity has been associated with CMA, indicating its pivotal role in tissue homeostasis. Since first studies associating Parkinson's disease (PD) to CMA dysfunction, increasing evidence points out that CMA is altered in both physiological and pathological brain aging. In this review article, we summarize the current knowledge regarding the impact of CMA during aging in brain physiopathology, highlighting the role of CMA in neurodegenerative diseases and glioblastoma, the most common and aggressive brain tumor in adults.