bims-agimec Biomed News
on Aging mechanisms
Issue of 2024–08–04
seven papers selected by
Metin Sökmen, Ankara Üniversitesi



  1. Aging Cell. 2024 Jul 30. e14268
      The determination of age-related transcriptional changes may contribute to the understanding of health and life expectancy. The broad application of results from age cohorts may have limitations. Altering sample sizes per time point or sex, using a single mouse strain or tissue, a limited number of replicates, or omitting the middle of life can bias the surveys. To achieve higher general validity and to identify less distinctive players, bulk RNA sequencing of a mouse cohort, including seven organs of two strains from both sexes of 5 ages, was performed. Machine learning by bootstrapped variable importance and selection methodology (Boruta) was used to identify common aging features where the circadian rhythms (CiR) transcripts appear as promising age markers in an unsupervised analysis. Pathways of 11 numerically analyzed local network clusters were affected and classified into four major gene expression profiles, whereby CiR and proteostasis candidates were particularly conspicuous with partially opposing changes. In a data-based interaction association network, the CiR-proteostasis axis occupies an exposed central position, highlighting its relevance. The computation of 11,830 individual transcript associations provides potential superordinate contributors, such as hormones, to age-related changes, as in CiR. In hormone-sensitive LNCaP cells, short-term supraphysiologic levels of the sex hormones dihydrotestosterone or estradiol increase the expression of the CiR transcript Bhlhe40 and the associated senescence regulator Cdkn2b (p15). According to these findings, the bilateral dysregulation of CiR appears as a fundamental protagonist of aging, whose transcripts could serve as a biological marker and its restoration as a therapeutic opportunity.
    Keywords:  Bhlhe40 (Dec1); aging hallmarks; circadian rhythms; interaction network; machine learning; mouse cohort; organ strain sex; sex hormones
    DOI:  https://doi.org/10.1111/acel.14268
  2. Geroscience. 2024 Jul 30.
      Healthy aging is a crucial goal in aging societies of the western world, with various lifestyle strategies being employed to achieve it. Among these strategies, hydrotherapy stands out for its potential to promote cardiovascular and mental health. Cold water therapy, a hydrotherapy technique, has emerged as a lifestyle strategy with the potential capacity to evoke a wide array of health benefits. This review aims to synthesize the extensive body of research surrounding cold water therapy and its beneficial effects on various health systems as well as the underlying biological mechanisms driving these benefits. We conducted a search for interventional and observational cohort studies from MEDLINE and EMBASE up to July 2024. Deliberate exposure of the body to cold water results in distinct physiological responses that may be linked to several health benefits. Evidence, primarily from small interventional studies, suggests that cold water therapy positively impacts cardiometabolic risk factors, stimulates brown adipose tissue and promotes energy expenditure-potentially reducing the risk of cardiometabolic diseases. It also triggers the release of stress hormones, catecholamines and endorphins, enhancing alertness and elevating mood, which may alleviate mental health conditions. Cold water therapy also reduces inflammation, boosts the immune system, promotes sleep and enhances recovery following exercise. The optimal duration and temperature needed to derive maximal benefits is uncertain but current evidence suggests that short-term exposure and lower temperatures may be more beneficial. Overall, cold water therapy presents a potential lifestyle strategy to enhancing physical and mental well-being, promoting healthy aging and extending the healthspan, but definitive interventional evidence is warranted.
    Keywords:  Cardiovascular disease; Cold water therapy; Healthspan; Hydrotherapy; Mortality
    DOI:  https://doi.org/10.1007/s11357-024-01295-w
  3. Front Nutr. 2024 ;11 1409339
      Considering a growing, aging population, the need for interventions to improve the healthspan in aging are tantamount. Diet and nutrition are important determinants of the aging trajectory. Plant-based diets that provide bioactive phytonutrients may contribute to offsetting hallmarks of aging and reducing the risk of chronic disease. Researchers now advocate moving toward a positive model of aging which focuses on the preservation of functional abilities, rather than an emphasis on the absence of disease. This narrative review discusses the modulatory effect of nutrition on aging, with an emphasis on promising phytonutrients, and their potential to influence cellular, organ and functional parameters in aging. The literature is discussed against the backdrop of a recent conceptual framework which describes vitality, intrinsic capacity and expressed capacities in aging. This aims to better elucidate the role of phytonutrients on vitality and intrinsic capacity in aging adults. Such a review contributes to this new scientific perspective-namely-how nutrition might help to preserve functional abilities in aging, rather than purely offsetting the risk of chronic disease.
    Keywords:  aging; healthspan; intrinsic capacity; nutrition; phytonutrients; vitality
    DOI:  https://doi.org/10.3389/fnut.2024.1409339
  4. Rev Cardiovasc Med. 2023 Mar;24(3): 82
      Cardiac aging is a natural process accompanied by cardiomyocyte hypertrophy and dysfunction. These changes can lead to adverse organ remodeling and ultimately lead to the development of heart failure. The study of cardiac aging is helpful to explore the mechanism of senescence and is of great significance for preventing cardiac aging. Cardiac aging is accompanied by changes in various metabolic functions. In this process, due to the change of metabolic substrates and enzyme activities, oxidative stress response increases, and reactive oxygen species (ROS) increases, accompanied by mitochondrial dysfunction and gene expression changes, so related protein metabolism also changes. Hormone metabolism and autophagy are also involved in the process of cardiac aging. Based on these findings, changes in diet, caloric restriction, improvement of mitochondrial function and promotion of autophagy have been proven to have positive effects in delaying cardiac aging. This article reviews the metabolic changes involved in the process of cardiac aging from different aspects, and briefly reviews the measures to improve cardiac aging.
    Keywords:  autophagy; cardiac aging; metabolism; metabolomics; mitochondria; signaling pathways
    DOI:  https://doi.org/10.31083/j.rcm2403082
  5. Front Endocrinol (Lausanne). 2024 ;15 1414350
      Bone homeostasis in physiology depends on the balance between bone formation and resorption, and in pathology, this homeostasis is susceptible to disruption by different influences, especially under ageing condition. Gut microbiota has been recognized as a crucial factor in regulating host health. Numerous studies have demonstrated a significant association between gut microbiota and bone metabolism through host-microbiota crosstalk, and gut microbiota is even an important factor in the pathogenesis of bone metabolism-related diseases that cannot be ignored. This review explores the interplay between gut microbiota and bone metabolism, focusing on the roles of gut microbiota in bone ageing and aging-related bone diseases, including osteoporosis, fragility fracture repair, osteoarthritis, and spinal degeneration from different perspectives. The impact of gut microbiota on bone metabolism during aging through modification of endocrinology system, immune system and gut microbiota metabolites are summarized, facilitating a better grasp of the pathogenesis of aging-related bone metabolic diseases. This review offers innovative insights into targeting the gut microbiota for the treatment of bone ageing-related diseases as a clinical therapeutic strategy.
    Keywords:  aging; bone; bone metabolism; gut microbiota; skeletal degenerative diseases
    DOI:  https://doi.org/10.3389/fendo.2024.1414350
  6. Mech Ageing Dev. 2024 Jul 30. pii: S0047-6374(24)00075-7. [Epub ahead of print] 111975
      Lymphatic aging represented by cellular and functional changes, is involved in increased geriatric disorders, but the intersection between aging and lymphatic modulation is less clear. Lymphatic vessels play an essential role in maintaining tissue fluid homeostasis, regulating immune function, and promoting macromolecular transport. Lymphangiogenesis and lymphatic remodeling following cellular senescence and organ deterioration are crosslinked with the progression of some lymphatic-associated diseases, e.g., atherosclerosis, inflammation, lymphoedema, and cancer. Age-related detrimental tissue changes may occur in lymphatic vessels with diverse etiologies, and gradually shift towards chronic low-grade inflammation, so-called inflammaging, and lead to decreased immune response. The investigation of the relationship between advanced age and organ deterioration is becoming an area of rapidly increasing significance in lymphatic biology and medicine. Here we highlight the emerging importance of lymphangiogenesis and lymphatic remodeling in the regulation of aging-related pathological processes, which will help to find new avenues for effective intervention to promote healthy aging.
    Keywords:  Aging; Lymphangiogenesis; Lymphatic-associated diseases; Macrophage; Senescence-associated secretory phenotype (SASP); VEGF-C/VEGFR-3
    DOI:  https://doi.org/10.1016/j.mad.2024.111975
  7. J Nutr Health Aging. 2024 Jul 26. pii: S1279-7707(24)00411-1. [Epub ahead of print]28(9): 100324
       BACKGROUND: Along with the ageing of society, the absolute prevalence of age-related diseases is expected to rise, leading to a substantial burden on healthcare systems and society. Thus, there is an urgent need to promote healthy ageing. As opposed to chronological age, biological age was introduced to accurately represent the ageing process, as it considers physiological deterioration that is linked to morbidity and mortality risk. Furthermore, biological age responds to various factors, including nutritional factors, which have the potential to mitigate the risk of age-related diseases. As a result, a promising biomarker of biological age known as the epigenetic clock has emerged as a suitable measure to investigate the direct relations between nutritional factors and ageing, thereby identifying potential intervention targets to improve healthy ageing.
    METHODS: In this study, we analysed data from 3,969 postmenopausal women from the Women's Health Initiative to identify nutrients that are associated with the rate of ageing by using an accurate measure of biological age called the PhenoAge epigenetic clock. We used Copula Graphical Models, a data-driven exploratory analysis tool, to identify direct relationships between nutrient intake and age-acceleration, while correcting for every variable in the dataset.
    RESULTS: We revealed that increased dietary intakes of coumestrol, beta-carotene and arachidic acid were associated with decelerated epigenetic ageing. In contrast, increased intakes of added sugar, gondoic acid, behenic acid, arachidonic acid, vitamin A and ash were associated with accelerated epigenetic ageing in postmenopausal women.
    CONCLUSION: Our study discovered direct relations between nutrients and epigenetic ageing, revealing promising areas for follow-up studies to determine the magnitude and causality of our estimated diet-epigenetic relationships.
    Keywords:  Copula graphical models; Epigenetic ageing; Epigenetic clock; Nutrition
    DOI:  https://doi.org/10.1016/j.jnha.2024.100324