scholarly journals Senolytics and the compression of late-life mortality

2021 ◽  
Author(s):  
Axel Kowald ◽  
Thomas B L Kirkwood
Keyword(s):  
Survival Data ◽  
Ageing Population ◽  
Molecular Processes ◽  
Maximum Lifespan ◽  
Repair Capacity ◽  
Treatment Regimens ◽  
Age Related ◽  
Cell Accumulation ◽  
Ageing Rate ◽  
Median Lifespan

AbstractSenescent cells play an important role in mammalian ageing and in the etiology of age-related diseases. Treatment of mice with senolytics – drugs that selectively remove senescent cells – causes an extension of median lifespan but has little effect on maximum lifespan. Postponement of some mortality to later ages, without a corresponding increase in maximum mortality, can be termed ‘compression of mortality’. When we fit the standard Gompertz mortality model to the survival data following senolytic treatment, we find an increase in the slope parameter, commonly described as the ‘actuarial ageing rate’. These observations raise important questions about the actions of senolytic treatments and their effects on health and survival, which are not yet sufficiently understood. To explore how the survival data from senolytics experiments might be explained, we combine recent exploration of the evolutionary basis of cellular senescence with theoretical consideration of the molecular processes that might be involved. We perform numerical simulations of senescent cell accumulation and senolytic treatment in an ageing population. The simulations suggest that while senolytics diminish the burden of senescent cells, they may also impair the general repair capacity of the organism, leading to a faster accumulation post-treatment of new senescent cells. Our results suggest a framework to address the benefits and possible side effects of senolytic therapies, with the potential to aid the design of optimal treatment regimens.

Vztah mezi presbyakuzí a poruchou kognitivních funkcí ve stáří PDF uzamčeno English info

2021 ◽  
Vol 70 (4) ◽  
pp. 223-233
Author(s):  
Jakub Fuksa ◽  
Milan Profant ◽  
Martin Chovanec ◽  
Josef Syka
Keyword(s):  
Hearing Loss ◽  
Cognitive Impairment ◽  
Hearing Aids ◽  
Cognitive Functions ◽  
Auditory Information ◽  
Ageing Population ◽  
Published Evidence ◽  
Age Related ◽  
Keywords Dementia ◽  
Increased Risk

Age-related hearing loss, presbycusis, is one of the most frequent sensory impairments in the ageing population. It is associated with pathologies of both inner ear and the central parts of the auditory system. Intact cognitive functions are necessary for the proper processing of complex auditory information. Since the beginning of the 80s, there is an increasing amount of evidence linking presbycusis to cognitive impairment and increased risk of dementia. The exact cause, which connects these two pathologies, is still unknown, although there are several hypotheses with various levels of evidence available. This review aims to describe the role of cognitive functions in the auditory processing, to summarize published evidence for a relationship between the hearing loss and cognitive impairment with a possible mechanism, which would explain this link. In addition, we discuss specific features of cognitive assessment in a person with hearing loss and describe the effect of hearing loss treatment, e. g. with hearing aids, cochlear implant and cognitive-hearing training on cognitive functions. Keywords: dementia – hearing loss – presbycusis – cognitive decline

scholarly journals Ferrous-glutathione coupling mediates ferroptosis and frailty in Caenorhabditis elegans

2019 ◽  
Author(s):  
Nicole L. Jenkins ◽  
Simon A. James ◽  
Agus Salim ◽  
Fransisca Sumardy ◽  
Terence P. Speed ◽  
...  
Keyword(s):  
Cell Death ◽  
Caenorhabditis Elegans ◽  
Ferrous Iron ◽  
Somatic Tissue ◽  
Glutathione Depletion ◽  
Death Process ◽  
C Elegans ◽  
Regulated Cell Death ◽  
Age Related ◽  
Ageing Rate

All eukaryotes require iron. Replication, detoxification, and a cancer-protective form of regulated cell death termed ferroptosis1, all depend on iron metabolism. Ferrous iron accumulates over adult lifetime in the Caenorhabditis elegans model of ageing2. Here we show that glutathione depletion is coupled to ferrous iron elevation in these animals, and that both occur in late life to prime cells for ferroptosis. We demonstrate that blocking ferroptosis, either by inhibition of lipid peroxidation or by limiting iron retention, mitigates age-related cell death and markedly increases lifespan and healthspan in C. elegans. Temporal scaling of lifespan is not evident when ferroptosis is inhibited, consistent with this cell death process acting at specific life phases to induce organismal frailty, rather than contributing to a constant ageing rate. Because excess age-related iron elevation in somatic tissue, particularly in brain3–5, is thought to contribute to degenerative disease6, 7, our data indicate that post-developmental interventions to limit ferroptosis may promote healthy ageing.

Degenerative cardiovascular disease in the elderly

ESC CardioMed ◽  
2018 ◽  
pp. 2960-2964
Author(s):  
Edgar Argulian
Keyword(s):  
Aortic Valve ◽  
Cardiac Fibrosis ◽  
Prognostic Significance ◽  
The Elderly ◽  
Degenerative Changes ◽  
Ageing Population ◽  
Mitral Annular Calcification ◽  
Aortic Valve Sclerosis ◽  
Age Related ◽  
Annular Calcification

The ageing population represents a unique challenge for cardiovascular care. Ageing causes remodelling of the cardiovascular system and commonly results in distinct degenerative changes. Most of these degenerative changes have significant interactions with cardiovascular risk factors by either being a marker of disease burden or being exaggerated by co-morbid conditions. Also, age-related degenerative conditions have physiological and prognostic implications. This chapter discusses several common degenerative cardiovascular conditions in the elderly such as cardiac fibrosis, amyloidosis, mitral annular calcification, and aortic valve sclerosis. Some of these conditions (such as cardiac fibrosis and amyloidosis) are implicated in pathogenesis of heart failure with preserved ejection fraction. Others (such as mitral annular calcification and aortic valve sclerosis) do not typically cause any measurable physiological abnormality but have prognostic significance.

scholarly journals Establishment of variation source and age-related reference interval models for 22 common biochemical analytes in older people using real-world big data mining

2020 ◽  
Vol 49 (6) ◽  
pp. 1062-1070
Author(s):  
Chaochao Ma ◽  
Liangyu Xia ◽  
Xinqi Chen ◽  
Jie Wu ◽  
Yicong Yin ◽  
...  
Keyword(s):  
Big Data ◽  
Older People ◽  
Real World ◽  
Reference Interval ◽  
Reference Intervals ◽  
Ageing Population ◽  
Factors Affecting ◽  
Age Related ◽  
The Status ◽  
Source Models

Abstract Background the ageing population has increased in many countries, including China. However, reference intervals (RIs) for older people are rarely established because of difficulties in selecting reference individuals. Here, we aimed to analyse the factors affecting biochemical analytes and establish RI and age-related RI models for biochemical analytes through mining real-world big data. Methods data for 97,220 individuals downloaded from electronic health records were included. Three derived databases were established. The first database included 97,220 individuals and was used to build age-related RI models after identifying outliers by the Tukey method. The second database consisted of older people and was used to establish variation source models and RIs for biochemical analytes. Differences between older and younger people were compared using the third database. Results sex was the main source of variation of biochemical analytes for older people in the variation source models. The distributions of creatinine and uric acid were significantly different in the RIs of biochemical analytes for older people established according to sex. Age-related RI models for biochemical analytes that were most affected by age were built and visualized, revealing various patterns of changes from the younger to older people. Conclusion the study analysed the factors affecting biochemical analytes in older people. Moreover, RI and age-related RI models of biochemical analytes for older people were established to provide important insight into biological processes and to assist clinical use of various biochemical analytes to monitor the status of various diseases for older people.

scholarly journals Epidemiological aspects of ageing

1997 ◽  
Vol 352 (1363) ◽  
pp. 1829-1835 ◽  
Author(s):  
Kay-Tee Khaw
Keyword(s):  
Heart Disease ◽  
Macular Degeneration ◽  
Smoking Habit ◽  
Ageing Population ◽  
Functional Impairments ◽  
Age Related ◽  
Secular Variations ◽  
Optimal Health ◽  
Societal Challenge ◽  
Adjusted Incidence

A major societal challenge is to improve quality of life and prevent or reduce disability and dependency in an ageing population. Increasing age is associated with increasing risk of disability and loss of independence, due to functional impairments such as loss of mobility, hearing and vision; a major issue must be how far disability can be prevented. Ageing is associated with loss of bone tissue, reduction in muscle mass, reduced respiratory function, decline in cognitive function, rise in blood pressure and macular degeneration which predispose to disabling conditions such as osteoporosis, heart disease, dementia and blindness. However, there are considerable variations in different communities in terms of the rate of age–related decline. Large geographic and secular variations in the age–adjusted incidence of major chronic diseases such as stroke, hip fracture, coronary heart disease, cancer, visual loss from cataract, glaucoma and macular degeneration suggest strong environmental determinants in diet, physical activity and smoking habit. The evidence suggests that a substantial proportion of chronic disabling conditions associated with ageing are preventable, or at least postponable and not an inevitable accompaniment of growing old. Postponement or prevention of these conditions may not only increase longevity, but, more importantly, reduce the period of illnesses such that the majority of older persons may live high–quality lives, free of disability, until very shortly before death. We need to understand better the factors influencing the onset of age–related disability in the population, so that we have appropriate strategies to maintain optimal health in an ageing population.

What you need to know about malnutrition in older adults

2020 ◽  
Vol 81 (9) ◽  
pp. 1-8
Author(s):  
Kerry Cheah ◽  
Amy Illsley
Keyword(s):  
Older Patients ◽  
Nutritional Assessment ◽  
Adult Population ◽  
Management Strategies ◽  
Community Dwelling ◽  
Nursing Home Care ◽  
Assessment Tools ◽  
Ageing Population ◽  
Age Related ◽  
Older Adult Population

Malnutrition is the disturbance of normal form or function, arising from the deficiency of one or more nutrients, and is a significant issue in the older adult population. Despite their reduced energy requirements, older patients need the same protein intake and micronutrients as younger patients, but age-related changes may impact the ability to meet these requirements. The cause of malnutrition in individuals is likely to be multifactorial and can therefore be complex to manage. Adequate nutrition is important for both community dwelling patients and inpatients, as malnutrition increases the risk of complications and the likelihood of needing residential or nursing home care on discharge. This article discusses the risk factors for the development of malnutrition in older patients and the different nutritional assessment tools available. Management strategies for optimising nutrition can be divided into systems and supplementation. With an ageing population, most doctors will inevitably become increasingly involved with treating older patients and this article highlights the need to consider a patient's nutritional status. Nutrition should be considered during every ward round and the multidisciplinary team as a whole should maintain an awareness and responsibility for managing malnutrition.

scholarly journals Rare Occurrence of a Poorly Differentiated Neuroendocrine Tumor of the Bladder

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Katherine Dowd ◽  
Charles Rotenberry ◽  
Douglas Russell ◽  
Mitchell Wachtel ◽  
Werner de Riese
Keyword(s):  
Cell Carcinoma ◽  
Neuroendocrine Tumor ◽  
Survival Data ◽  
Large Cell Carcinoma ◽  
Large Cell ◽  
Disease Recurrence ◽  
Small Cell ◽  
Treatment Regimens ◽  
Poorly Differentiated ◽  
Carcinoma Of The Bladder

Neuroendocrine tumors rarely occur in the urinary bladder. They can be carcinomatous, subdivided into small cell and large cell pathology. Small cell carcinoma of the bladder is a rarity that may present at an advanced pathologic stage. No treatment regimens have been standardized for local or metastatic disease. Review of the recent literature shows equivalent survival data for localized disease treated with chemoradiotherapy combined with either bladder sparing surgery or radical cystectomy. Patients with significant comorbidities are an additional challenge. We report a case of poorly differentiated neuroendocrine tumor of the bladder, which could not be classified as small or large cell carcinoma, complicated by significant comorbidities. After management with transurethral resection of the tumor, adjuvant chemotherapy, and radiation, the patient is alive and asymptomatic nearly 1 year after initial TURBT with no evidence of disease recurrence.

scholarly journals New Insights into the Chemical and Biochemical Basis of the “Yang-Invigorating” Action of Chinese Yang-Tonic Herbs

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Jihang Chen ◽  
Hoi Shan Wong ◽  
Pou Kuan Leong ◽  
Hoi Yan Leung ◽  
Wing Man Chan ◽  
...  
Keyword(s):  
Functional Capacity ◽  
Antioxidant Response ◽  
Mitochondrial Uncoupling ◽  
Biochemical Basis ◽  
Age Related ◽  
Mitochondrial Ros ◽  
Transport Chain ◽  
Median Lifespan ◽  
Bodily Function ◽  
Increased Activity

In the practice of traditional Chinese medicine, many Yang-tonic herbs have been used for retarding the decline in bodily function and delaying the onset of age-related diseases. Our earlier studies have demonstrated that Yang-invigorating herbs/formulations protect against oxidative injury in various organs and also extend the median lifespan in mice. This lifespan extension was associated with an upregulation of cellular antioxidant status including that of mitochondria whose functional capacity is also increased by “Yang-invigorating” herbs/formulations. In this paper, we propose that triterpenes and phytosterols, which are ubiquitously found in Yang-tonic herbs, may be the chemical entities responsible for enhancing mitochondrial functional and antioxidant capacity and thus the “Yang-invigorating” action. The biochemical mechanism underlying this “Yang-invigorating” action may involve a sustained production of low levels of mitochondrial reactive oxygen species (ROS) secondary to an increased activity of the electron transport chain, with the possible involvement of mitochondrial uncoupling. The increase in mitochondrial functional capacity can retard the decline in bodily function during aging, whereas the mitochondrial ROS production is instrumental in eliciting a glutathione antioxidant response via redox-sensitive signaling pathways, which can delay the onset of age-related diseases.

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