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Nature Metabolism May 2024Ageing is a conserved biological process, modulated by intrinsic and extrinsic factors, that leads to changes in life expectancy. In humans, ageing is characterized by... (Review)
Review
Ageing is a conserved biological process, modulated by intrinsic and extrinsic factors, that leads to changes in life expectancy. In humans, ageing is characterized by greatly increased prevalence of cardiometabolic disease, type 2 diabetes and disorders associated with impaired immune surveillance. Adipose tissue displays species-conserved, temporal changes with ageing, including redistribution from peripheral to central depots, loss of thermogenic capacity and expansion within the bone marrow. Adipose tissue is localized to discrete depots, and also diffusely distributed within multiple organs and tissues in direct proximity to specialized cells. Thus, through their potent endocrine properties, adipocytes are capable of modulating tissue and organ function throughout the body. In addition to adipocytes, multipotent progenitor/stem cells in adipose tissue play a crucial role in maintenance and repair of tissues throughout the lifetime. Adipose tissue may therefore be a central driver for organismal ageing and age-associated diseases. Here we review the features of adipose tissue during ageing, and discuss potential mechanisms by which these changes affect whole-body metabolism, immunity and longevity. We also explore the potential of adipose tissue-targeted therapies to ameliorate age-associated disease burdens.
Topics: Humans; Aging; Adipose Tissue; Animals; Adipocytes; Longevity
PubMed: 38783156
DOI: 10.1038/s42255-024-01046-3 -
Journal of Psychiatric Practice May 2024
Topics: Humans; Aging
PubMed: 38819240
DOI: 10.1097/PRA.0000000000000788 -
International Journal of Molecular... Oct 2023Aging is a natural, gradual, and inevitable process associated with a series of changes at the molecular, cellular, and tissue levels that can lead to an increased risk... (Review)
Review
Aging is a natural, gradual, and inevitable process associated with a series of changes at the molecular, cellular, and tissue levels that can lead to an increased risk of many diseases, including cancer. The most significant changes at the genomic level (DNA damage, telomere shortening, epigenetic changes) and non-genomic changes are referred to as hallmarks of aging. The hallmarks of aging and cancer are intertwined. Many studies have focused on genomic hallmarks, but non-genomic hallmarks are also important and may additionally cause genomic damage and increase the expression of genomic hallmarks. Understanding the non-genomic hallmarks of aging and cancer, and how they are intertwined, may lead to the development of approaches that could influence these hallmarks and thus function not only to slow aging but also to prevent cancer. In this review, we focus on non-genomic changes. We discuss cell senescence, disruption of proteostasis, deregualation of nutrient sensing, dysregulation of immune system function, intercellular communication, mitochondrial dysfunction, stem cell exhaustion and dysbiosis.
Topics: Humans; Aging; Cellular Senescence; Cell Communication; Telomere Shortening; Neoplasms
PubMed: 37895144
DOI: 10.3390/ijms242015468 -
Nutrients Feb 2024Magnesium is an essential ion in the human body that regulates numerous physiological and pathological processes. Magnesium deficiency is very common in old age.... (Review)
Review
Magnesium is an essential ion in the human body that regulates numerous physiological and pathological processes. Magnesium deficiency is very common in old age. Age-related chronic diseases and the aging process itself are frequently associated with low-grade chronic inflammation, called 'inflammaging'. Because chronic magnesium insufficiency has been linked to excessive generation of inflammatory markers and free radicals, inducing a chronic inflammatory state, we formerly hypothesized that magnesium inadequacy may be considered among the intermediaries helping us explain the link between inflammaging and aging-associated diseases. We show in this review evidence of the relationship of magnesium with all the hallmarks of aging (genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, disabled autophagy, dysbiosis, and chronic inflammation), which may positively affect the human healthspan. It is feasible to hypothesize that maintaining an optimal balance of magnesium during one's life course may turn out to be a safe and economical strategy contributing to the promotion of healthy aging. Future well-designed studies are necessary to further explore this hypothesis.
Topics: Humans; Magnesium; Epigenesis, Genetic; Aging; Cellular Senescence; Inflammation
PubMed: 38398820
DOI: 10.3390/nu16040496 -
Nature Jun 2024Senescence is a cellular state linked to ageing and age-onset disease across many mammalian species. Acutely, senescent cells promote wound healing and prevent tumour...
Senescence is a cellular state linked to ageing and age-onset disease across many mammalian species. Acutely, senescent cells promote wound healing and prevent tumour formation; but they are also pro-inflammatory, thus chronically exacerbate tissue decline. Whereas senescent cells are active targets for anti-ageing therapy, why these cells form in vivo, how they affect tissue ageing and the effect of their elimination remain unclear. Here we identify naturally occurring senescent glia in ageing Drosophila brains and decipher their origin and influence. Using Activator protein 1 (AP1) activity to screen for senescence, we determine that senescent glia can appear in response to neuronal mitochondrial dysfunction. In turn, senescent glia promote lipid accumulation in non-senescent glia; similar effects are seen in senescent human fibroblasts in culture. Targeting AP1 activity in senescent glia mitigates senescence biomarkers, extends fly lifespan and health span, and prevents lipid accumulation. However, these benefits come at the cost of increased oxidative damage in the brain, and neuronal mitochondrial function remains poor. Altogether, our results map the trajectory of naturally occurring senescent glia in vivo and indicate that these cells link key ageing phenomena: mitochondrial dysfunction and lipid accumulation.
Topics: Animals; Female; Humans; Male; Aging; Brain; Cellular Senescence; Drosophila melanogaster; Fibroblasts; Lipid Metabolism; Longevity; Mitochondria; Neuroglia; Neurons; Oxidative Stress; Transcription Factor AP-1; Lipids; Inflammation
PubMed: 38839958
DOI: 10.1038/s41586-024-07516-8 -
Ageing Research Reviews Feb 2024This paper addresses how long lifespan can be extended via multiple interventions, such as dietary supplements [e.g., curcumin, resveratrol, sulforaphane, complex... (Review)
Review
This paper addresses how long lifespan can be extended via multiple interventions, such as dietary supplements [e.g., curcumin, resveratrol, sulforaphane, complex phytochemical mixtures (e.g., Moringa, Rhodiola)], pharmaceutical agents (e.g., metformin), caloric restriction, intermittent fasting, exercise and other activities. This evaluation was framed within the context of hormesis, a biphasic dose response with specific quantitative features describing the limits of biological/phenotypic plasticity for integrative biological endpoints (e.g., cell proliferation, memory, fecundity, growth, tissue repair, stem cell population expansion/differentiation, longevity). Evaluation of several hundred lifespan extending agents using yeast, nematode (Caenorhabditis elegans), multiple insect and other invertebrate and vertebrate models (e.g., fish, rodents), revealed they responded in a manner [average (mean/median) and maximum lifespans] consistent with the quantitative features [i.e., 30-60% greater at maximum (Hormesis Rule)] of the hormetic dose response. These lifespan extension features were independent of biological model, inducing agent, endpoints measured and mechanism. These findings indicate that hormesis describes the capacity to extend life via numerous agents and activities and that the magnitude of lifespan extension is modest, in the percentage, not fold, range. These findings have important implications for human aging, genetic diseases/environmental stresses and lifespan extension, as well as public health practices and long-term societal resource planning.
Topics: Animals; Humans; Longevity; Hormesis; Aging; Caenorhabditis elegans; Stress, Physiological
PubMed: 38182079
DOI: 10.1016/j.arr.2023.102181 -
Seminars in Hematology Feb 2024Clonal hematopoiesis (CH) has been associated with aging, occurring in about 10% of individuals aged >70 years, and immune dysfunction. Aged hematopoietic stem and... (Review)
Review
Clonal hematopoiesis (CH) has been associated with aging, occurring in about 10% of individuals aged >70 years, and immune dysfunction. Aged hematopoietic stem and progenitor cells exhibit pathological changes in immune function and activation of inflammatory pathways. CH clones commonly harbor a loss of function mutation in DNMT3A or TET2, which causes increased expression of inflammatory signaling genes, a proposed mechanism connected to CH and the development of age-related diseases. Additionally, inflammation may stress the hematopoietic compartment, driving the expansion of mutant clones. While the epidemiologic overlap between CH, hematologic malignancies, and atherosclerotic cardiovascular diseases has been reported, the mechanisms linking these concepts are largely unknown and merit much further investigation. Here, we review studies highlighting the interplay between CH, inflamm-aging, the immune system, and the prevalence of CH in autoimmune diseases.
Topics: Humans; Clonal Hematopoiesis; Autoimmunity; Hematopoiesis; Aging; Mutation; Autoimmune Diseases
PubMed: 38423847
DOI: 10.1053/j.seminhematol.2024.01.012 -
Scientific Reports May 2024Alongside rapid population ageing, we are experiencing increasing numbers of people with cognitive impairment and dementia. There is great scientific effort being...
Alongside rapid population ageing, we are experiencing increasing numbers of people with cognitive impairment and dementia. There is great scientific effort being committed to understanding cognitive and brain functioning, with the aim of helping to promote healthy ageing and independence, and improve quality of life. This Cognitive Ageing Collection brings together cutting-edge research using a variety of methods and from diverse disciplinary perspectives, with example topics including cognitive strategies, genetic risk factors, and emotion regulation. Articles in the Collection highlight advances in our understanding of cognitive and brain health, and outline important directions for future research.
Topics: Humans; Cognitive Aging; Cognition; Aging
PubMed: 38740780
DOI: 10.1038/s41598-024-60763-7 -
Ugeskrift For Laeger Jan 2024Age is a crucial prognostic factor across clinical specialities with significant implications for medical practice. Increasingly, "biological age" is being used as a... (Review)
Review
Age is a crucial prognostic factor across clinical specialities with significant implications for medical practice. Increasingly, "biological age" is being used as a more relevant age marker in a clinical context and is heavily integrated into the medical use of AI. This review describes the current knowledge about molecular biological and genetic aging-related changes associated with the genome and epigenome, used for biological age determination. It explores the potential causes of these changes and provides an update on treatment status and "rejuvenation" of these genome-related factors.
Topics: Humans; Genome, Human; Aging; Rejuvenation
PubMed: 38235775
DOI: 10.61409/V08230536 -
Cell Metabolism May 2024Bone is an endocrine organ that participates in whole-body homeostasis. The biology of bone-derived osteokines, however, remains unclear. Liang et al. integrate...
Bone is an endocrine organ that participates in whole-body homeostasis. The biology of bone-derived osteokines, however, remains unclear. Liang et al. integrate experimental and computational methods to discover new osteokines, establish their cell of origin and target site, and study their role in aging and during mechanical stress.
Topics: Humans; Animals; Bone and Bones; Aging; Stress, Mechanical
PubMed: 38718755
DOI: 10.1016/j.cmet.2024.04.008