-
Mechanisms of Ageing and Development Apr 2020With the emergence of diseases, people become frailer and are expected to be less tolerant of adverse outcomes. Frailty was first described to explain the variability in... (Review)
Review
With the emergence of diseases, people become frailer and are expected to be less tolerant of adverse outcomes. Frailty was first described to explain the variability in life expectancy in individuals of the same age. Nowadays, it is described as a syndrome and as a state. It is used to explain the heterogeneity of people not only in their responses to biological ageing but also in their responses to illness. In this review, we explore the role of frailty both in age-related diseases, including dementia, cancer and cardiovascular disease, and in non-age-related diseases, such as Human Immunodeficiency Virus. We describe how high levels of frailty in such disorders predict worse outcomes and play a direct role in disease progression and in prognostic prediction. Overall, the potential for frailty to predict adverse health outcomes among young people as well as in non-age-related diseases is an evolving topic. Understanding how frailty contributes to poor health and how it can be modified to prevent or delay disease progression will ultimately enhance quality of life in affected individuals.
Topics: Aged; Aged, 80 and over; Aging; Frail Elderly; Frailty; Humans; Risk Factors
PubMed: 32088282
DOI: 10.1016/j.mad.2020.111217 -
Ageing Research Reviews May 2017The first clinical trial aimed at targeting fundamental processes of aging will soon be launched (TAME: Targeting Aging with Metformin). In its wake is a robust pipeline... (Review)
Review
The first clinical trial aimed at targeting fundamental processes of aging will soon be launched (TAME: Targeting Aging with Metformin). In its wake is a robust pipeline of therapeutic interventions that have been demonstrated to extend lifespan or healthspan of preclinical models, including rapalogs, antioxidants, anti-inflammatory agents, and senolytics. This ensures that if the TAME trial is successful, numerous additional clinical trials are apt to follow. But a significant impediment to these trials remains the question of what endpoints should be measured? The design of the TAME trial very cleverly skirts around this based on the fact that there are decades of data on metformin in humans, providing unequaled clarity of what endpoints are most likely to yield a positive outcome. But for a new chemical entity, knowing what endpoints to measure remains a formidable challenge. For economy's sake, and to achieve results in a reasonable time frame, surrogate markers of lifespan and healthy aging are desperately needed. This review provides a comprehensive analysis of molecular endpoints that are currently being used as indices of age-related phenomena (e.g., morbidity, frailty, mortality) and proposes an approach for validating and prioritizing these endpoints.
Topics: Aging; Biomarkers; Humans; Life Expectancy; Longevity; Pathology, Molecular
PubMed: 27721062
DOI: 10.1016/j.arr.2016.09.012 -
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 -
Journal of Medical Ethics May 2024Räsänen draws a distinction between chronological age and biological age and argues that biological ageing is (sometimes) desirable. To demonstrate this, he asks us to...
Räsänen draws a distinction between chronological age and biological age and argues that biological ageing is (sometimes) desirable. To demonstrate this, he asks us to consider the case of April, who like Karel Čapek's Elina Makropulos, has stopped biologically ageing. Unlike Makropulos, though, April's biological ageing was halted before puberty, so she will never mature into adulthood. Räsänen contends this case shows ageing can be desirable, but this equivocates between maturing and ageing. Here I argue biological ageing, or the wear and tear normally associated with chronological ageing, is undesirable, but that maturing can be desirable.
Topics: Humans; Aging; Female; Sexual Maturation
PubMed: 37553223
DOI: 10.1136/jme-2023-109418 -
Biogerontology Dec 2018
Topics: Aging; Cellular Senescence; Humans; Metabolomics; Microbiota; Proteomics
PubMed: 30288632
DOI: 10.1007/s10522-018-9776-2 -
The Journal of Physiology Apr 2016Ageing in humans is associated with a significant increase in the prevalence of cardiovascular disease. We still do not fully understand the molecular mechanisms... (Review)
Review
Ageing in humans is associated with a significant increase in the prevalence of cardiovascular disease. We still do not fully understand the molecular mechanisms underpinning this correlation. However, a number of insights into which genes control cardiac ageing have come from studying hearts of the fruit fly, Drosophila melanogaster. The fly's simple heart tube has similar molecular structure and basic physiology to the human heart. Also, both fly and human hearts experience significant age-related morphological and functional decline. Studies on the fly heart have highlighted the involvement of key nutrient sensing, ion channel and sarcomeric genes in cardiac ageing. Many of these genes have also been implicated in ageing of the mammalian heart. Genes that increase oxidative stress, or are linked to cardiac hypertrophy or neurodegenerative diseases in mammals also affect cardiac ageing in the fruit fly. Moreover, fly studies have demonstrated the potential of exercise and statins to treat age-related cardiac disease. These results show the value of Drosophila as a model to discover the genetic causes of human cardiac ageing.
Topics: Aging; Animals; Drosophila melanogaster; Heart; Humans; Myocardium
PubMed: 26060055
DOI: 10.1113/JP270563 -
Aging Aug 2018The regenerative capacity of the liver after resection is reduced with aging. Recent studies on rodents revealed that both intracellular and extracellular factors are... (Review)
Review
The regenerative capacity of the liver after resection is reduced with aging. Recent studies on rodents revealed that both intracellular and extracellular factors are involved in the impairment of liver mass recovery during aging. Among the intracellular factors, age-dependent decrease of BubR1 (budding uninhibited by benzimidazole-related 1), YAP (Yes-associated protein) and SIRT1 (Sirtuin-1) have been associated to dampening of tissue reconstitution and inhibition of cell cycle genes following partial hepatectomy. Extra-cellular factors, such as age-dependent changes in hepatic stellate cells affect liver regeneration through inhibition of progenitor cells and reduction of liver perfusion. Furthermore, chronic release of pro-inflammatory proteins by senescent cells (SASP) affects cell proliferation suggesting that senescent cell clearance might improve tissue regeneration. Accordingly, young plasma restores liver regeneration in aged animals through autophagy re-establishment. This review will discuss how intracellular and extracellular factors cooperate to guarantee a proper liver regeneration and the possible causes of its impairment during aging. The possibility that an improvement of the liver regenerative capacity in elderly might be achieved through elimination of senescent cells autophagy or by administration of direct mitogenic agents devoid of cytotoxicity will also be entertained.
Topics: Aging; Animals; Cellular Senescence; Gene Expression Regulation; Liver; Liver Regeneration; Mice
PubMed: 30157472
DOI: 10.18632/aging.101524 -
Ageing Research Reviews Jul 2017Alternative splicing is a co-transcriptional process, which allows for the production of multiple transcripts from a single gene and is emerging as an important control... (Review)
Review
Alternative splicing is a co-transcriptional process, which allows for the production of multiple transcripts from a single gene and is emerging as an important control point for gene expression. Alternatively expressed isoforms often have antagonistic function and differential temporal or spatial expression patterns, yielding enormous plasticity and adaptability to cells and increasing their ability to respond to environmental challenge. The regulation of alternative splicing is critical for numerous cellular functions in both pathological and physiological conditions, and deregulated alternative splicing is a key feature of common chronic diseases. Isoform choice is controlled by a battery of splicing regulatory proteins, which include the serine arginine rich (SRSF) proteins and the heterogeneous ribonucleoprotein (hnRNP) classes of genes. These important splicing regulators have been implicated in age-related disease, and in the ageing process itself. This review will outline the important contribution of splicing regulator proteins to ageing and age-related disease.
Topics: Aging; Alternative Splicing; Animals; Cardiovascular Diseases; Heterogeneous-Nuclear Ribonucleoprotein Group A-B; Humans; RNA, Messenger
PubMed: 28456680
DOI: 10.1016/j.arr.2017.04.004 -
Expert Opinion on Therapeutic Targets Apr 2017In the present paper, the authors have discussed anti-aging strategies which aim to slow the aging process and to delay the onset of age-related diseases, focusing on... (Review)
Review
In the present paper, the authors have discussed anti-aging strategies which aim to slow the aging process and to delay the onset of age-related diseases, focusing on nutrient sensing pathways (NSPs) as therapeutic targets. Indeed, several studies have already demonstrated that both in animal models and humans, dietary interventions might have a positive impact on the aging process through the modulation of these pathways. Areas covered: Achieving healthy aging is the main challenge of the twenty-first century because lifespan is increasing, but not in tandem with good health. The authors have illustrated different approaches that can act on NSPs, modulating the rate of the aging process. Expert opinion: Humanity's lasting dream is to reverse or, at least, postpone aging. In recent years, increasing attention has been devoted to anti-aging therapies. The subject is very popular among the general public, whose imagination runs wild with all the possible tools to delay aging and to gain immortality. Some approaches discussed in the present review should be able to substantially slow down the aging process, extending our productive, youthful lives, without frailty.
Topics: Age Factors; Aging; Animals; Diet; Dietary Supplements; Humans; Longevity; Nutritional Physiological Phenomena
PubMed: 28281903
DOI: 10.1080/14728222.2017.1294684 -
Ageing Research Reviews Nov 2018Cancer and ageing can be regarded as two different manifestations of the same underlying process-accumulation of cellular damage-and therefore both are closely linked.... (Review)
Review
Cancer and ageing can be regarded as two different manifestations of the same underlying process-accumulation of cellular damage-and therefore both are closely linked. Nowadays, the ageing of populations worldwide is leading to an unprecedented increase in cancer cases and fatalities, and therefore the understanding of links between cancer and ageing is more important than ever. Spalax is considered an excellent model for ageing and, additionally, for cancer research, due to not show clear age-related phenotypic changes and not develop spontaneous tumours, despite its relatively long lifespan (∼20 years in captivity). Thereby, the purpose of this review is to summarize the recent knowledge on Spalax, with a particular emphasis on the molecular mechanisms associated with their longevity and cancer resistance.
Topics: Aging; Animals; Cell Hypoxia; Humans; Neoplasms; Spalax; Species Specificity
PubMed: 29913210
DOI: 10.1016/j.arr.2018.06.004