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Ageing Research Reviews Jan 2022Improvements in public health and health care have resulted in significant increases in lifespan globally, but also in a significant increase in chronic disease... (Review)
Review
Improvements in public health and health care have resulted in significant increases in lifespan globally, but also in a significant increase in chronic disease prevalence. This has led to a focus on healthy ageing bringing a shift from a pathology-centered to an intrinsic capacity and function-centered view. In parallel, the emerging field of geroscience has promoted the exploration of the biomolecular drivers of ageing towards a transverse vision by proposing an integrated set of molecular hallmarks. In this review, we propose to take a step further in this direction, highlighting a gerophysiological perspective that considers the notion of homeostasis/allostasis relating to robustness/fragility respectively. While robustness is associated with homeostasis achieved by an optimal structure/function relationship in all organs, successive repair processes occurring after daily injuries and infections result in accumulation of scar healing leading to progressive tissue degeneration, allostasis and frailty. Considering biological ageing as the accumulation of scarring at the level of the whole organism emphasizes three transverse and shared elements in the body - mesenchymal stroma cells/immunity/metabolism (SIM). This SIM tryptich drives tissue and organ fate to regulate the age-related evolution of body functions. It provides the basis of a gerophysiology perspective, possibly representing a better way to decipher healthy ageing, not only by defining a composite biomarker(s) but also by developing new preventive/curative strategies.
Topics: Aging; Frailty; Geroscience; Healthy Aging; Humans; Longevity
PubMed: 34883201
DOI: 10.1016/j.arr.2021.101537 -
Ageing Research Reviews Nov 2020As human life expectancy keeps increasing, ageing populations present a growing challenge for clinical practices. Human ageing is associated with molecular, structural,... (Review)
Review
As human life expectancy keeps increasing, ageing populations present a growing challenge for clinical practices. Human ageing is associated with molecular, structural, and functional changes in a variety of organ systems, including the kidney. During the ageing process, the kidney experiences progressive functional decline as well as macroscopic and microscopic histological alterations, which are accentuated by systemic comorbidities like hypertension and diabetes mellitus, or by preexisting or underlying kidney diseases. Although ageing per se does not cause kidney injury, physiologic changes associated with normal ageing processes are likely to impair the reparative capacity of the kidney and thus predispose older people to acute kidney disease, chronic kidney disease and other renal diseases. Mechanistically, cell senescence plays a key role in renal ageing, involving a number of cellular signaling mechanisms, many of which may be harnessed as international targets for slowing or even reversing kidney ageing. This review summarizes the clinical characteristics of renal ageing, highlights the latest progresses in deciphering the role of cell senescence in renal ageing, and envisages potential interventional strategies and novel therapeutic targets for preventing or improving renal ageing in the hope of maintaining long-term kidney health and function across the life course.
Topics: Aged; Aged, 80 and over; Aging; Cellular Senescence; Humans; Hypertension; Kidney
PubMed: 32835891
DOI: 10.1016/j.arr.2020.101151 -
Signal Transduction and Targeted Therapy Jun 2021Remarkable progress in ageing research has been achieved over the past decades. General perceptions and experimental evidence pinpoint that the decline of physical... (Review)
Review
Remarkable progress in ageing research has been achieved over the past decades. General perceptions and experimental evidence pinpoint that the decline of physical function often initiates by cell senescence and organ ageing. Epigenetic dynamics and immunometabolic reprogramming link to the alterations of cellular response to intrinsic and extrinsic stimuli, representing current hotspots as they not only (re-)shape the individual cell identity, but also involve in cell fate decision. This review focuses on the present findings and emerging concepts in epigenetic, inflammatory, and metabolic regulations and the consequences of the ageing process. Potential therapeutic interventions targeting cell senescence and regulatory mechanisms, using state-of-the-art techniques are also discussed.
Topics: Aging; Cell Differentiation; Cellular Senescence; Epigenomics; Humans; Inflammation
PubMed: 34176928
DOI: 10.1038/s41392-021-00646-9 -
Nature Reviews. Cardiology Jan 2021The number of old people is rising worldwide, and advancing age is a major risk factor for atherosclerotic cardiovascular disease. However, the mechanisms underlying... (Review)
Review
The number of old people is rising worldwide, and advancing age is a major risk factor for atherosclerotic cardiovascular disease. However, the mechanisms underlying this phenomenon remain unclear. In this Review, we discuss vascular intrinsic and extrinsic mechanisms of how ageing influences the pathology of atherosclerosis. First, we focus on factors that are extrinsic to the vasculature. We discuss how ageing affects the development of myeloid cells leading to the expansion of certain myeloid cell clones and induces changes in myeloid cell functions that promote atherosclerosis via inflammation, including a potential role for IL-6. Next, we describe vascular intrinsic factors by which ageing promotes atherogenesis - in particular, the effects on mitochondrial function. Studies in mice and humans have shown that ageing leads to a decline in vascular mitochondrial function and impaired mitophagy. In mice, ageing is associated with an elevation in the levels of the inflammatory cytokine IL-6 in the aorta, which participates in a positive feedback loop with the impaired vascular mitochondrial function to accelerate atherogenesis. We speculate that vascular and myeloid cell ageing synergize, via IL-6 signalling, to accelerate atherosclerosis. Finally, we propose future avenues of clinical investigation and potential therapeutic approaches to reduce the burden of atherosclerosis in old people.
Topics: Aging; Atherosclerosis; Humans; Interleukin-6
PubMed: 32918047
DOI: 10.1038/s41569-020-0431-7 -
Nature Metabolism Aug 2022Ageing is the largest risk factor for many chronic diseases. Studies of heterochronic parabiosis, substantiated by blood exchange and old plasma dilution, show that...
Ageing is the largest risk factor for many chronic diseases. Studies of heterochronic parabiosis, substantiated by blood exchange and old plasma dilution, show that old-age-related factors are systemically propagated and have pro-geronic effects in young mice. However, the underlying mechanisms how bloodborne factors promote ageing remain largely unknown. Here, using heterochronic blood exchange in male mice, we show that aged mouse blood induces cell and tissue senescence in young animals after one single exchange. This induction of senescence is abrogated if old animals are treated with senolytic drugs before blood exchange, therefore attenuating the pro-geronic influence of old blood on young mice. Hence, cellular senescence is neither simply a response to stress and damage that increases with age, nor a chronological cell-intrinsic phenomenon. Instead, senescence quickly and robustly spreads to young mice from old blood. Clearing senescence cells that accumulate with age rejuvenates old circulating blood and improves the health of multiple tissues.
Topics: Aging; Animals; Cellular Senescence; Male; Mice; Parabiosis
PubMed: 35902645
DOI: 10.1038/s42255-022-00609-6 -
Ageing Research Reviews Feb 2022The process of senescence (aging) is predominantly determined by the action of wild-type genes. For most organisms, this does not reflect any adaptive function that... (Review)
Review
The process of senescence (aging) is predominantly determined by the action of wild-type genes. For most organisms, this does not reflect any adaptive function that senescence serves, but rather evolutionary effects of declining selection against genes with deleterious effects later in life. To understand aging requires an account of how evolutionary mechanisms give rise to pathogenic gene action and late-life disease, that integrates evolutionary (ultimate) and mechanistic (proximate) causes into a single explanation. A well-supported evolutionary explanation by G.C. Williams argues that senescence can evolve due to pleiotropic effects of alleles with antagonistic effects on fitness and late-life health (antagonistic pleiotropy, AP). What has remained unclear is how gene action gives rise to late-life disease pathophysiology. One ultimate-proximate account is T.B.L. Kirkwood's disposable soma theory. Based on the hypothesis that stochastic molecular damage causes senescence, this reasons that aging is coupled to reproductive fitness due to preferential investment of resources into reproduction, rather than somatic maintenance. An alternative and more recent ultimate-proximate theory argues that aging is largely caused by programmatic, developmental-type mechanisms. Here ideas about AP and programmatic aging are reviewed, particularly those of M.V. Blagosklonny (the hyperfunction theory) and J.P. de Magalhães (the developmental theory), and their capacity to make sense of diverse experimental findings is assessed.
Topics: Aging; Biological Evolution; Biology; Humans; Longevity; Reproduction
PubMed: 34990845
DOI: 10.1016/j.arr.2021.101557 -
Nature Reviews. Endocrinology May 2020With the ageing of the global population, interest is growing in the 'geroscience hypothesis', which posits that manipulation of fundamental ageing mechanisms will delay... (Review)
Review
With the ageing of the global population, interest is growing in the 'geroscience hypothesis', which posits that manipulation of fundamental ageing mechanisms will delay (in parallel) the appearance or severity of multiple chronic, non-communicable diseases, as these diseases share the same underlying risk factor - namely, ageing. In this context, cellular senescence has received considerable attention as a potential target in preventing or treating multiple age-related diseases and increasing healthspan. Here we review mechanisms of cellular senescence and approaches to target this pathway therapeutically using 'senolytic' drugs that kill senescent cells or inhibitors of the senescence-associated secretory phenotype (SASP). Furthermore, we highlight the evidence that cellular senescence has a causative role in multiple diseases associated with ageing. Finally, we focus on the role of cellular senescence in a number of endocrine diseases, including osteoporosis, metabolic syndrome and type 2 diabetes mellitus, as well as other endocrine conditions. Although much remains to be done, considerable preclinical evidence is now leading to the initiation of proof-of-concept clinical trials using senolytics for several endocrine and non-endocrine diseases.
Topics: Aging; Animals; Cellular Senescence; Endocrine System Diseases; Humans; Risk Factors
PubMed: 32161396
DOI: 10.1038/s41574-020-0335-y -
Mechanisms of Ageing and Development Jan 2019Ageing is today a major societal concern that is intrinsically associated with the increase of life expectancy. Outside the context of severe degenerative diseases that... (Review)
Review
Ageing is today a major societal concern that is intrinsically associated with the increase of life expectancy. Outside the context of severe degenerative diseases that affect the elderly populations, normal visible signs of ageing, notably skin sagging and wrinkles, influence the social and individual perception of peoples. Accordingly, there is a strong demand for researches on skin ageing. Deciphering the cellular and molecular processes of skin evolution through ageing is thus an active scientific domain, at the frontier of tissue developmental and ageing biology. The focus of the present article is to provide an overview of the current knowledge concerning the evolution of dermis characteristics at different life stages, from intra-uterine to post-natal life. The description will integrate stage-specific and age-related changes in dermis characteristics at the tissue, cell, and molecular levels.
Topics: Aging; Animals; Dermis; Extracellular Matrix; Humans; Skin Aging
PubMed: 29548941
DOI: 10.1016/j.mad.2018.03.006 -
Gerontology 2023The world's population is ageing, and most older adults experience a later life burdened with disease and disability. Frailty is a multidimensional and dynamic condition... (Review)
Review
Frailty: Pathophysiology, Theoretical and Operational Definition(s), Impact, Prevalence, Management and Prevention, in an Increasingly Economically Developed and Ageing World.
The world's population is ageing, and most older adults experience a later life burdened with disease and disability. Frailty is a multidimensional and dynamic condition characterized by declines in reserve and function across multiple physiological systems, such that the ability to cope with every day or acute stressors becomes compromised. It is projected to become one of the most serious public health challenges economically developed societies will face in the coming century. This review provides a comprehensive overview of frailty, exploring its pathophysiology, theoretical and operational definition(s), impact, prevalence, management, and prevention, within the context of its emergence as a major public health challenge, in an increasingly economically developed and ageing world. Further, this review discusses the major limitations, deficiencies, and knowledge gaps presently within the field, and future research directions pertinent to the advancement of frailty research and the promotion of healthy longevity among the increasing global population of older adults.
Topics: Humans; Aged; Frailty; Prevalence; Aging; Longevity; Health Status; Frail Elderly
PubMed: 36476630
DOI: 10.1159/000528561 -
Ugeskrift For Laeger Jun 2023This review focuses on ageing and sleep. A key focus in aging is to improve senescence by extending good health, optimal cognitive function, and medical and social... (Review)
Review
This review focuses on ageing and sleep. A key focus in aging is to improve senescence by extending good health, optimal cognitive function, and medical and social assistance into later life. Given that one third of the human lifespan is spent sleeping, the importance of maintaining deep, stable, and consistent sleep is self-evident for the good life quality expected and optimal daytime functioning, which the aging process always curtails. For this reason, employees in the health system should know and focus on the expected changes in sleep patterns and disturbances from young adults to old age, including possible disorders and treatments.
Topics: Humans; Young Adult; Aging; Cognition; Longevity; Quality of Life; Sleep; Aged
PubMed: 37381876
DOI: No ID Found