Age-associated molecular changes are deleterious and may modulate life span through diet

Lee, Sang Goo; Kaya, Alaattin; Avanesov, Andrei; Podolskiy, Dmitriy I.; Song, Eun Ju; Go, Du-Min; Jin, Gwi-Deuk; Hwang, Jae Yeon; Kim, Eun Bae; Kim, Dae-Yong; Gladyshev, Vadim N.

doi:10.1126/sciadv.1601833

Cited by 11 publications

(5 citation statements)

References 37 publications

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“…Our study includes 77 samples with ages between 60 and 99 years, 19 of them older than 90, thus providing substantial coverage of the advanced age interval. Yet, we detect no significant increase in numbers of detected lipids and individual variation with increased age, which was predicted by the metabolic damage accumulation hypothesis of aging [37][38][39]54]. At the same time, increases in metabolite numbers at advanced age were reported in Drosophila [37].…”

Section: Lipidome Changes In Agingcontrasting

confidence: 55%

“…Some of the proposed mechanisms of aging predict increases in numbers of detected compounds at advanced age due to metabolic dysfunction and other age-related deregulation [37][38][39]. We detected 10,185 ± 791, 11,203 ± 794, 11,637 ± 909, and 11,912 ± 662 lipids at infant, child, juvenile, and adult stages, indicating a progressive increase in the lipidome complexity of human PFC from infants to adults (ANOVA, P < 0.0001; Fig.…”

Section: Pfc Lipidome Alterations At Advanced Agementioning

confidence: 99%

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Lipidome alterations in human prefrontal cortex during development, aging, and cognitive disorders

Zubkov

et al. 2018

Mol Psychiatry

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Lipids are essential to brain functions, yet they remain largely unexplored. Here we investigated the lipidome composition of prefrontal cortex gray matter in 396 cognitively healthy individuals with ages spanning 100 years, as well as 67 adult individuals diagnosed with autism (ASD), schizophrenia (SZ), and Down syndrome (DS). Of the 5024 detected lipids, 95% showed significant age-dependent concentration differences clustering into four temporal stages, and resulting in a gradual increase in membrane fluidity in individuals ranging from newborn to nonagenarian. Aging affects 14% of the brain lipidome with late-life changes starting predominantly at 50-55 years of age-a period of general metabolic transition. All three diseases alter the brain lipidome composition, leading-among other things-to a concentration decrease in glycerophospholipid metabolism and endocannabinoid signaling pathways. Lipid concentration decreases in SZ were further linked to genetic variants associated with disease, indicating the relevance of the lipidome changes to disease progression.

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Section: Lipidome Changes In Agingcontrasting

confidence: 55%

Section: Pfc Lipidome Alterations At Advanced Agementioning

confidence: 99%

Lipidome alterations in human prefrontal cortex during development, aging, and cognitive disorders

Zubkov

et al. 2018

Mol Psychiatry

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“…The gut microbiota suffers extensive changes across a lifetime as a result of age, diet, environment, and disease (86,123). A significant body of evidence shows such modifications in the microbiota of model organisms (e.g., flies, fish, mice, and humans).…”

Section: Aging Alters the Microbiotamentioning

confidence: 99%

The Microbiome and Aging

2019

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Aging is a natural process of organismal decay that underpins the development of myriad diseases and disorders. Extensive efforts have been made to understand the biology of aging and its regulation, but most studies focus solely on the host organism. Considering the pivotal role of the microbiota in host health and metabolism, we propose viewing the host and its microbiota as a single biological entity whose aging phenotype is influenced by the complex interplay between host and bacterial genetics. In this review we present how the microbiota changes as the host ages, but also how the intricate relationship between host and indigenous bacteria impacts organismal aging and life span. In addition, we highlight other microbiota-dependent mechanisms that potentially regulate aging, and present experimental animal models for addressing these questions. Importantly, we propose microbiome dysbiosis as an additional hallmark and biomarker of aging.

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“…Probiotic diets have been associated with beneficial life span effects in a mouse study 23 , and human centenarians and ultra-centenarians are characterised by a gut microbial composition enriched in health-associated bacteria 24 . Studies in yeast, flies and mice humans have shown that the gut microbiota undergoes dramatic changes during the ageing process 20 , 25 – 27 , raising the question of whether these changes are a consequence or a cause of ageing. Experimental work in flies showed that, upon ageing, commensal microbes can lead to dysbiosis, which is followed by loss of barrier function and ultimately host demise 28 .…”

Section: Ageing and The Microbiotamentioning

confidence: 99%

The role of the gut microbiome during host ageing

Seidel

Valenzano

2018

F1000Res

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Gut microbial communities participate in key aspects of host biology, including development, nutrient absorption, immunity and disease. During host ageing, intestinal microbes undergo dramatic changes in composition and function and can shift from commensal to pathogenic. However, whether they play a causal role in host ageing and life span has remained an open question for a long time. Recent work in model organisms has revealed for the first time that gut microbes can modulate ageing, opening new questions and opportunities to uncover novel ageing-modulating mechanisms and to design anti-ageing interventions by targeting the gut microbiota.

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Age-associated molecular changes are deleterious and may modulate life span through diet

Abstract: Age-associated molecular changes are deleterious and causally linked with aging and may affect life span through diet.

Cited by 11 publications

References 37 publications

Lipidome alterations in human prefrontal cortex during development, aging, and cognitive disorders

Lipidome alterations in human prefrontal cortex during development, aging, and cognitive disorders

The Microbiome and Aging

The role of the gut microbiome during host ageing

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