Premature aging in chronic kidney disease and chronic obstructive pulmonary disease

Kooman, Jeroen P.; Shiels, Paul G.; Stenvinkel, Peter

doi:10.1097/mco.0000000000000218

Cited by 10 publications

(11 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To our knowledge, this is the first demonstration of segmental aging in the mammalian brain. A similar phenomenon could be present in diseases associated with the accelerated ageing phenotype, including chronic kidney disease (CKD), obstructive pulmonary disease (COPD) or viral infections (HIV, HCV) [12,13,31,32,33,34]. …”

Section: Discussionmentioning

confidence: 86%

Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat

Khojah

Payne

McGuinness

et al. 2016

Cells

View full text Add to dashboard Cite

There is a paucity of information on the molecular biology of aging processes in the brain. We have used biomarkers of aging (SA β-Gal, p16Ink4a, Sirt5, Sirt6, and Sirt7) to demonstrate the presence of an accelerated aging phenotype across different brain regions in the AS/AGU rat, a spontaneous Parkinsonian mutant of PKCγ derived from a parental AS strain. P16INK4a expression was significantly higher in AS/AGU animals compared to age-matched AS controls (p < 0.001) and displayed segmental expression across various brain regions. The age-related expression of sirtuins similarly showed differences between strains and between brain regions. Our data clearly show segmental aging processes within the rat brain, and that these are accelerated in the AS/AGU mutant. The accelerated aging, Parkinsonian phenotype, and disruption to dopamine signalling in the basal ganglia in AS/AGU rats, suggests that this rat strain represents a useful model for studies of development and progression of Parkinson’s disease in the context of biological aging and may offer unique mechanistic insights into the biology of aging.

show abstract

Section: Discussionmentioning

confidence: 86%

Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat

Khojah

Payne

McGuinness

et al. 2016

Cells

View full text Add to dashboard Cite

show abstract

“…Vice versa, it has been proposed that chronic organ diseases, such as chronic obstructive pulmonary disease and chronic kidney disease, accelerate the aging process and thus lead to analogous phenotypes, such as muscle wasting, osteoporosis, and vascular aging (3). Acceleration of organismal aging due to failure of a major organ system, such as renal or respiratory impairment, has obvious implications for the assessment and care of patients affected by chronic debilitating diseases.…”

mentioning

confidence: 99%

Aging of the Immune System. Mechanisms and Therapeutic Targets

2016

View full text Add to dashboard Cite

Beginning with the sixth decade of life, the human immune system undergoes dramatic aging-related changes, which continuously progress to a state of immunosenescence. The aging immune system loses the ability to protect against infections and cancer and fails to support appropriate wound healing. Vaccine responses are typically impaired in older individuals. Conversely, inflammatory responses mediated by the innate immune system gain in intensity and duration, rendering older individuals susceptible to tissue-damaging immunity and inflammatory disease. Immune system aging functions as an accelerator for other age-related pathologies. It occurs prematurely in some clinical conditions, most prominently in patients with the autoimmune syndrome rheumatoid arthritis (RA); and such patients serve as an informative model system to study molecular mechanisms of immune aging. T cells from patients with RA are prone to differentiate into proinflammatory effector cells, sustaining chronic-persistent inflammatory lesions in the joints and many other organ systems. RA T cells have several hallmarks of cellular aging; most importantly, they accumulate damaged DNA. Because of deficiency of the DNA repair kinase ataxia telangiectasia mutated, RA T cells carry a higher burden of DNA double-strand breaks, triggering cell-indigenous stress signals that shift the cell's survival potential and differentiation pattern. Immune aging in RA T cells is also associated with metabolic reprogramming; specifically, with reduced glycolytic flux and diminished ATP production. Chronic energy stress affects the longevity and the functional differentiation of older T cells. Altered metabolic patterns provide opportunities to therapeutically target the immune aging process through metabolic interference.

show abstract

“…Many age-related morbidities share an underlying pathophysiological mechanism linked to ageing processes and thus present with a premature ageing phenotype [4] , [5] . Such phenotypes can be a direct result of disruption of cellular homeostasis, which can be further accelerated by both environmental factors and intrinsic metabolic activity leading to the generation of oxidative stress/damage, endoplasmic reticulum stress and mitochondrial dysfunction [3] , [6] .…”

Section: Introductionmentioning

confidence: 99%

“…A direct link between increasing allostatic load and all-cause mortality has been established in longitudinal studies [9] . Links between allostatic load and specific health outcomes or disease (cardiovascular disease, diabetes, osteoporosis, chronic kidney disease and chronic obstructive pulmonary disease), as well as a general decline in physical and cognitive function, have also been established [4] , [10] , [11] , [12] , [13] . Furthermore, the occurrence of age-related disorders has also been linked with the dysregulation of normal immune responses involved in the clearance of resident senescent cells within tissues.…”

Section: Introductionmentioning

confidence: 99%

Circulating markers of ageing and allostatic load: A slow train coming

Shiels

Stenvinkel

Kooman

et al. 2017

Practical Laboratory Medicine

Self Cite

View full text Add to dashboard Cite

Dealing with the growing burden of age-related morbidities is one of the greatest challenges facing modern society. How we age across the lifecourse and how psychosocial and lifestyle factors interplay with the biology of ageing remains to be fully elucidated. Sensitive and specific biomarkers with which to interrogate the biology of the ageing process are sparse. Recent evidence suggests that non-coding RNAs are key determinants of such processes and that these can be used as potential circulatory bio-markers of ageing. They may also provide a mechanism which mediates the spread of allostatic load across the body over time, ultimately reflecting the immunological health and physiological status of tissues and organs. The interplay between exosomal microRNAs and ageing processes is still relatively unexplored, although circulating microRNAs have been linked to the regulation of a range of physiological and pathological processes and offer insight into mechanistic determinants of healthspan.

show abstract

Premature aging in chronic kidney disease and chronic obstructive pulmonary disease

Abstract: An increased understanding of the premature aging process as well as its systemic consequences may pave the way for 'precision' intervention as well as shared treatment opportunities between chronic debilitating diseases of various causes.

Cited by 10 publications

References 61 publications

Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat

Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat

Aging of the Immune System. Mechanisms and Therapeutic Targets

Circulating markers of ageing and allostatic load: A slow train coming

Contact Info

Product

Resources

About