-
Mechanisms of Ageing and Development Mar 2018Cellular senescence was first described by Hayflick and Moorhead in the 1960s as the irreversible arrest of cells following prolonged cultivation. Telomere shortening is... (Review)
Review
Cellular senescence was first described by Hayflick and Moorhead in the 1960s as the irreversible arrest of cells following prolonged cultivation. Telomere shortening is the key mechanism driving replicative senescence in human fibroblasts. Later, pioneering work by Olivier Toussaint and others showed that stress plays a major role in the induction of senescence in vitro, a phenomenon known as stress-induced premature senescence or SIPS. It is also now widely accepted that senescence plays a role in vivo. An emerging body of evidence from animal models, and particularly mice, has demonstrated an important role for senescence in several processes such as embryonic development, wound healing, tumour suppression and ageing. However, mostly due to a lack of availability of tissues and specific markers, less is known about the importance of cell senescence in humans. In this review, we summarize some of the key findings in the field of senescence, stress-induced senescence and telomeres. We focus particularly on the role of telomere dysfunction and senescence during the ageing process as well as potential interventions, including pharmacological approaches like telomerase activators and senolytics, to counteract their detrimental effects in ageing and disease.
Topics: Aging; Cellular Senescence; Embryonic Development; Humans; Neoplasms; Stress, Physiological; Telomere Homeostasis; Wound Healing
PubMed: 28688962
DOI: 10.1016/j.mad.2017.07.001 -
Neurodegenerative Disease Management 2015Ageing Summit, London, UK, 10-12 February 2015 The Ageing Summit 2015 held on 10-12 February 2015 in London (UK) provided an extensive update to our knowledge of the...
Ageing Summit, London, UK, 10-12 February 2015 The Ageing Summit 2015 held on 10-12 February 2015 in London (UK) provided an extensive update to our knowledge of the 'Biology of Ageing' and a forum to discuss the participants' latest research progress. The meeting was subdivided into four thematic sessions: cellular level research including the aging brain; slowing down progression, rejuvenation and self-repair; genetic and epigenetic regulation; and expression and pathology of age-related diseases. Each session included multiple key presentations, three to five short research communications and ongoing poster presentations. The meeting provided an exciting multidisciplinary overview of the aging process from cellular and molecular mechanisms to medico-social aspects of human aging.
Topics: Aging; Animals; Brain; Epigenesis, Genetic; Humans; London
PubMed: 26107317
DOI: 10.2217/nmt.15.17 -
Cells Feb 2022In this review, we seek a novel strategy for establishing a rejuvenating microenvironment through senescent cells specific reprogramming. We suggest that partial... (Review)
Review
In this review, we seek a novel strategy for establishing a rejuvenating microenvironment through senescent cells specific reprogramming. We suggest that partial reprogramming can produce a secretory phenotype that facilitates cellular rejuvenation. This strategy is desired for specific partial reprogramming under control to avoid tumour risk and organ failure due to loss of cellular identity. It also alleviates the chronic inflammatory state associated with ageing and secondary senescence in adjacent cells by improving the senescence-associated secretory phenotype. This manuscript also hopes to explore whether intervening in cellular senescence can improve ageing and promote damage repair, in general, to increase people's healthy lifespan and reduce frailty. Feasible and safe clinical translational protocols are critical in rejuvenation by controlled reprogramming advances. This review discusses the limitations and controversies of these advances' application (while organizing the manuscript according to potential clinical translation schemes) to explore directions and hypotheses that have translational value for subsequent research.
Topics: Aging; Cellular Reprogramming; Cellular Senescence; Humans; Longevity; Rejuvenation
PubMed: 35269453
DOI: 10.3390/cells11050830 -
Mechanisms of Ageing and Development Oct 2016
Topics: Aging; Animals; Cellular Senescence; Endothelial Progenitor Cells; Humans
PubMed: 27634556
DOI: 10.1016/j.mad.2016.09.002 -
Medecine Sciences : M/S Dec 2020Cellular senescence has been now shown to be at the root of many degenerative processes that characterize ageing. Thus, in addition to an irreversible proliferative... (Review)
Review
Cellular senescence has been now shown to be at the root of many degenerative processes that characterize ageing. Thus, in addition to an irreversible proliferative arrest following various stresses or inappropriate stimuli, cellular senescence leads to genetic, epigenetic, metabolic, structural and functional adaptations of the cell. Moreover, senescence phenotype spreads to the surrounding tissue through a specific secretory profile. Eliminating or blocking the action of senescent cells by senotherapeutic agents prevents tissue degeneration and improves the longevity in preclinical models. In this review, we will present the latest applications in senotherapy and discuss the very promising results of the first recently published clinical trials.
Topics: Aging; Animals; Cellular Senescence; Drug Development; Epigenomics; Humans; Longevity; Pharmaceutical Preparations; Phenotype; Therapies, Investigational
PubMed: 33296630
DOI: 10.1051/medsci/2020220 -
Acta Bio-medica : Atenei Parmensis Jun 2018Biogerontology is the study of the biological basis of ageing and age-related diseases. The phenomenon and the process of ageing are well understood in evolutionary and... (Review)
Review
Biogerontology is the study of the biological basis of ageing and age-related diseases. The phenomenon and the process of ageing are well understood in evolutionary and biological terms; and a conceptual framework has been established within which general principles of ageing and longevity can be formulated. The phenotype of ageing in terms of progressive loss of physical function and fitness is best seen during the period of survival after the evolution-determined essential lifespan (ELS) of a species. However, the ageing phenotype is highly heterogenous and individualistic at all levels from the whole body to the molecular one. Most significantly, the process and the progression of ageing are not determined by any specific gerontogenes. Ageing is the result of imperfect maintenance and repair systems that allow a progressive shrinkage of the homeodynamic space of an individual. The challenge is to develop and apply wholistic approaches to the complex trait of ageing for maintaining and/or improving health. One such approach is that of mild stress-induced physiological hormesis by physical, mental and nutritional hormetins. Biogerontological research offers numerous opportunities for developing evidence-based novel biomedical technologies for maintaining and improving health, for preventing the onset of age-related diseases, and for extending the health-span.
Topics: Aging; Epigenesis, Genetic; Geriatrics; Humans; Longevity
PubMed: 29957767
DOI: 10.23750/abm.v89i2.7403 -
Age and Ageing Jul 2023Cellular senescence has emerged as a fundamental biological mechanism underpinning the ageing process and has been implicated in the pathogenesis of an increasing number...
Cellular senescence has emerged as a fundamental biological mechanism underpinning the ageing process and has been implicated in the pathogenesis of an increasing number of age-related conditions. Cellular senescence is a cell fate originally defined as an irreversible loss of replicative potential although it is now clear that it can be induced by a variety of mechanisms independent of replication and telomere attrition. The drivers include a persistent DNA damage response causing multiple alterations in cellular function. Senescent cells secrete a range of mediators that drive chronic inflammation and can convert other cells to the senescent state-the senescence-associated secretory phenotype. Much research to date has been conducted in animal models, but it is now clear that senescent cells accompany ageing in humans and their presence is an important driver of disease across systems. Proof-of-concept work suggests that preventing or reversing senescence may be a viable strategy to counteract human ageing and age-related disease. Possible interventions include exercise, nutrition and senolytics/senostatic drugs although there are a number of potential limitations to the use of senotherapeutics. These interventions are generally tested for single-organ conditions, but the real power of this approach is the potential to tackle multiple age-related conditions. The litmus test for this exciting new class of therapies, however, will be whether they can improve healthy life expectancy rather than merely extending lifespan. The outcomes measured in clinical studies need to reflect these aims if senotherapeutics are to gain the trust of clinicians, patients and the public.
Topics: Animals; Humans; Senotherapeutics; Cellular Senescence; Aging; Longevity; Inflammation
PubMed: 37466640
DOI: 10.1093/ageing/afad127 -
The National Medical Journal of India 1997
Topics: Aged; Aging; Cognition; Female; Humans; Life Expectancy; Life Style; Male; Middle Aged
PubMed: 9401386
DOI: No ID Found -
Biogerontology Feb 2011Aging is caused by gradual accumulation of cell and tissue damage. Accumulation of damage begins early and continues progressively throughout life, resulting after... (Review)
Review
UNLABELLED
Aging is caused by gradual accumulation of cell and tissue damage. Accumulation of damage begins early and continues progressively throughout life, resulting after several decades in the overt frailty, disability and diseases associated with aging. In Serbia during the last few years, several different institutions participated in the investigation in the aging process: (1) Changes in hormone signaling with aging-the age-related increase in insulinemia and glucose metabolism deregulation was found to be attributed to changes in insulin signaling as demonstrated on murine models. (2) Changes in immunological response in aging-along with involution of thymic lymphoepithelial tissue, it has been demonstrated on a murine model that early thymocyte differentiational steps within the CD4-8-double negative developmental stage are age-sensitive. (3) Changes in cholesterol metabolism and oxidative processes in aging-the beneficial effect of long-term dietary restriction on ageing, was explained as effect on cholesterol metabolism. (4) Alzheimer's disease-the connection between neurodegenerative processes associated to the Alzheimer's disease and the function of the Na-K-ATPase which is known to be altered by ageing has been experimentally shown.
CONCLUSION
The recent work of Serbian investigators suggest some new evidence that aging process influences the hormone signaling, immunological response, cholesterol metabolism and oxidative processes.
Topics: Aged; Aging; Animals; Biomedical Research; Geriatrics; Humans; Serbia
PubMed: 20401693
DOI: 10.1007/s10522-010-9275-6 -
Mechanisms of Ageing and Development Jan 2017Ageing is a multifactorial process affected by cumulative physiological changes resulting from stochastic processes combined with genetic factors, which together alter... (Review)
Review
Ageing is a multifactorial process affected by cumulative physiological changes resulting from stochastic processes combined with genetic factors, which together alter metabolic homeostasis. Genetic variation in maintenance of genome stability is emerging as an important determinant of ageing pace. Genome instability is also closely associated with a broad spectrum of conditions involving brain degeneration. Similarities and differences can be found between ageing-associated decline of brain functionality and the detrimental effect of genome instability on brain functionality and development. This review discusses these similarities and differences and highlights cell classes whose role in these processes might have been underestimated-glia and microglia.
Topics: Aging; Animals; Brain; Genomic Instability; Humans; Microglia; Neurodegenerative Diseases
PubMed: 27041231
DOI: 10.1016/j.mad.2016.03.011