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Molecular Oncology Sep 2022Advancing age is a major risk factor for malignant transformation and the development of cancer. As such, over 50% of neoplasms occur in individuals over the age of 70.... (Review)
Review
Advancing age is a major risk factor for malignant transformation and the development of cancer. As such, over 50% of neoplasms occur in individuals over the age of 70. The pathologies of both ageing and cancer have been characterized by respective groups of molecular hallmarks, and while some features are divergent between the two pathologies, several are shared. Perturbed mitochondrial function is one such common hallmark, and this observation therefore suggests that mitochondrial alterations may be of significance in age-related cancer development. There is now considerable evidence documenting the accumulation of somatic mitochondrial DNA (mtDNA) mutations in ageing human postmitotic and replicative tissues. Similarly, mutations of the mitochondrial genome have been reported in human cancers for decades. The plethora of functions in which mitochondria partake, such as oxidative phosphorylation, redox balance, apoptosis and numerous biosynthetic pathways, manifests a variety of ways in which alterations in mtDNA may contribute to tumour growth. However, the specific mechanisms by which mtDNA mutations contribute to tumour progression remain elusive and often contradictory. This review aims to consolidate current knowledge and describe future direction within the field.
Topics: Aging; DNA, Mitochondrial; Humans; Mitochondria; Mutation; Neoplasms
PubMed: 35842901
DOI: 10.1002/1878-0261.13291 -
Developmental Biology Aug 2021Recent advances in rapid medical detection and diagnostic technology have extended both human health and life expectancy. However, ageing remains one of the critical... (Review)
Review
Recent advances in rapid medical detection and diagnostic technology have extended both human health and life expectancy. However, ageing remains one of the critical risk factors in contributing to major incapacitating and fatal conditions, including cancer and neurodegeneration. Therefore, it is vital to study how ageing attributes to (or participates in) endangering human health via infliction of age-related diseases and what must be done to tackle this intractable process. This review encompasses the most recent literature elaborating the role of cell competition (CC) during ageing. CC is a process that occurs between two heterogeneous populations, where the cells with higher fitness levels have a competitive advantage over the neighbouring cells that have comparatively lower fitness levels. This interaction results in the selection of the fit cells, within a population, and elimination of the viable yet suboptimal cells. Therefore, it is tempting to speculate that, if this quality control mechanism works efficiently throughout life, can it ultimately lead to a healthier ageing and extended lifespan. Furthermore, the review aims to collate all the important state of the art publications that provides evidence of the relevance of CC in dietary restriction, stem cell dynamics, and cell senescence, thus, prompting us to advocate its contribution and in exploring new avenues and opportunities in fighting age-related conditions.
Topics: Aging; Animals; Cell Communication; Cell Competition; Cellular Senescence; Humans; Neoplasms
PubMed: 33753080
DOI: 10.1016/j.ydbio.2021.03.009 -
Behavioural Neurology 2015
Topics: Aging; Humans; Neurodegenerative Diseases
PubMed: 26185358
DOI: 10.1155/2015/149532 -
Experimental Physiology Sep 2017What is the topic of this review? The reasons for the continuing increase in human life expectancy are examined in the light of progress in understanding the... (Review)
Review
What is the topic of this review? The reasons for the continuing increase in human life expectancy are examined in the light of progress in understanding the physiological basis of ageing. Prospects for further extending the health span - the period free of age-related disability and disease - are critically assessed. What advances does it highlight? No active programming directly causes ageing, which instead results as a side effect of how evolution optimises the physiological allocation of resources between growth, reproduction and maintenance. Under pressure of natural selection, there was insufficient priority in maintaining the body well enough that it could endure without progressive accumulation of multiple kinds of molecular and cellular damage. Understanding human ageing is a major challenge for the physiological sciences. It is made all the more urgent by the survival of inreasing numbers of people to advanced old age and by a shift in the underlying causes of the continuing increase in life expectancy. The previous increase was caused almost entirely by the prevention of deaths in the early and middle years of life; a process that has seen such success that in developed countries there remains little scope for significant further increase from this cause. The more recent increase is driven by something new. We are reaching old age in generally better health, and it is the death rates at advanced ages that are now falling fast. At the same time, biology has established that there is almost certainly no fixed programme for ageing, which is caused instead by the lifelong accumulation of damage. It is becoming evident that the ageing process is much more malleable than we used to think. We need urgently to establish the factors that govern this malleability and to identify the interactions between, on the one hand, intrinsic biological processes that drive the many chronic diseases and disabilities for which age is by far the largest risk factor and, on the other hand, the social and lifestyle factors that influence our individual trajectories of health in old age. Ageing is no longer as mysterious and intractable a process as used to be thought, offering new opportunities for contributions from other branches of the physiological sciences.
Topics: Aging; Animals; Chronic Disease; Humans; Life Expectancy; Selection, Genetic
PubMed: 28768061
DOI: 10.1113/EP086205 -
F1000Research 2019The field of aging research has progressed significantly over the past decades. Exogenously and endogenously inflicted molecular damage ranging from genotoxic to... (Review)
Review
The field of aging research has progressed significantly over the past decades. Exogenously and endogenously inflicted molecular damage ranging from genotoxic to organellar damage drives the aging process. Repair mechanisms and compensatory responses counteract the detrimental consequences of the various damage types. Here, we discuss recent progress in understanding cellular mechanisms and interconnections between signaling pathways that control longevity. We summarize cell-autonomous and non-cell-autonomous mechanisms that impact the cellular and organismal aging process.
Topics: Aging; DNA Damage; Humans; Longevity; Signal Transduction
PubMed: 31448092
DOI: 10.12688/f1000research.19610.1 -
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 -
Mammalian Genome : Official Journal of... Aug 2016Stem cells maintain homeostasis in all regenerating tissues during the lifespan of an organism. Thus, age-related functional decline of such tissues is likely to be at... (Review)
Review
Stem cells maintain homeostasis in all regenerating tissues during the lifespan of an organism. Thus, age-related functional decline of such tissues is likely to be at least partially explained by molecular events occurring in the stem cell compartment. Some of these events involve epigenetic changes, which may dictate how an aging genome can lead to differential gene expression programs. Recent technological advances have made it now possible to assess the genome-wide distribution of an ever-increasing number of epigenetic marks. As a result, the hypothesis that there may be a causal role for an altered epigenome contributing to the functional decline of cells, tissues, and organs in aging organisms can now be explored. In this paper, we review recent developments in the field of epigenetic regulation of stem cells, and how this may contribute to aging.
Topics: Aging; Cellular Senescence; DNA Methylation; Epigenesis, Genetic; Genome; Homeostasis; Humans; Regeneration; Stem Cells
PubMed: 27229519
DOI: 10.1007/s00335-016-9645-8 -
Journal of Parkinson's Disease 2022Ageing is a major risk factor for most neurodegenerative diseases, including Parkinson's disease (PD). Progressive age-related dysregulation of the immune system is... (Review)
Review
Ageing is a major risk factor for most neurodegenerative diseases, including Parkinson's disease (PD). Progressive age-related dysregulation of the immune system is termed immunosenescence and is responsible for the weakened response to novel antigens, increased susceptibility to infections and reduced effectiveness of vaccines seen in the elderly. Immune activation, both within the brain and periphery, is heavily implicated in PD but the role of immunosenescence has not been fully explored. Studies to date provide some evidence for an attenuation in immunosenescence in PD, particularly a reduction in senescent CD8 T lymphocytes in PD cases compared to similarly aged controls. Here, we discuss recent evidence of age-related immune abnormalities in PD with a focus on T cell senescence and explore their potential role in disease pathogenesis and development.
Topics: Aged; Aging; Cellular Senescence; Humans; Immunosenescence; Parkinson Disease; T-Lymphocytes
PubMed: 35661020
DOI: 10.3233/JPD-223228 -
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 -
Current Biology : CB Jul 2016The trade-off between survival and reproduction is the bedrock of the evolutionary theory of ageing. The reproductive system regulates ageing of the soma, and removal of... (Review)
Review
The trade-off between survival and reproduction is the bedrock of the evolutionary theory of ageing. The reproductive system regulates ageing of the soma, and removal of germ cells extends somatic lifespan and increases resistance to a broad variety of abiotic and biotic stresses. The general explanation for this somatic response is that reduced reproduction frees up resources for survival. Remarkably, however, the disruption of molecular signaling pathways that regulate ageing increases lifespan without the obligatory reduction in fecundity, thus challenging the key role of the survival-reproduction trade-off. Here, we review the diverse literature on the costs of lifespan extension and suggest that the current paradigm is overly centered on the trade-off between lifespan and fecundity, often neglecting key aspects of fitness, such as development time, defense against parasites and, in particular, the high costs of germline maintenance. Compromised germline maintenance increases germline mutation rate, which reduces offspring fitness and ultimately can terminate germline proliferation across generations. We propose that future work should incorporate the costs of germline maintenance in the study of ageing evolution, as well as in applied biomedical research, by assessing offspring fitness.
Topics: Aging; Biological Evolution; Costs and Cost Analysis; Germ Cells; Humans; Reproduction
PubMed: 27404253
DOI: 10.1016/j.cub.2016.04.012