Organelle aging: Lessons from model organisms

Bouska, Mark; Huang, Kerui; Kang, Ping; Bai, Hua

doi:10.1016/j.jgg.2019.03.011

Cited by 15 publications

(9 citation statements)

References 202 publications

(269 reference statements)

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“…In the transient mTor knockdown group, 327 genes were significantly differentially spliced, compared to 17 of continuous mTor knockdown and 4 specific to mTor knockdown in late life. KEGG analysis in the transient mTor knockdown group were enriched for differentially spliced variants associated with endocytosis 39 , the lysosome 40 , Hippo signalling (potentially mediating longevity through autophagy 41 and FOXO 42 ) and mTor signalling itself (Table S7). Thus, potentially the long-lasting mortality benefits from transient mTor reduction are mediated by long-lasting changes in alternative splicing, as predicted from the upregulation of the spliceosome 43 .…”

Section: Resultsmentioning

confidence: 99%

Age-dependent effects of reduced mTor signalling on life expectancy through distinct physiology

Simons

Hartshorne

Trooster

et al. 2019

Preprint

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12Research on the mechanisms of ageing has identified ways via which lifespan can 13 be extended in model organisms, increasing the potential for translation of these 14 findings to our own species. However, the large majority of research on animal 15 models involves dietary, genetic or pharmacological treatments throughout life -16 limiting translational potential and ignoring age-dependent effects. Previously, we 17 have suggested using demographic meta-analysis that reduced mTor signalling has 18 the potential to instantly rejuvenate. We have now tested this prediction 19 experimentally using large-scale demographic data (N > 10,000) combined with 20 conditional knockdown of mTor in Drosophila melanogaster. Indeed, reduced mTor 21 decreased mortality rate when applied during old age. Interestingly, we found that 22 transient treatment during early adult life had long-lasting benefits. Age-dependent 23 deep-RNAseq indicated that these effects arose from distinct physiology and 24 implicate alternative splicing as a potential mechanism for the long-lasting benefits of 25 transient mTor reduction. These findings suggest that reducing mTor short term or 26 during old age could be used to combat ageing. In addition, our findings suggest that 27 the results from experimental research on mTor signalling, and potentially other 28 mechanisms of ageing, that employ life-long interventions are likely to be a complex 29 composite of age-dependent effects that counteract or enhance each other. 30 157 effects cox proportional hazard models correcting for cage effects (see methods 14,31 ). B) Transient 158 mTor knockdown (maximum induction of GeneSwitch at blue dotted line) resulted in a modest 159 increase in mortality during early life, but subsequently resulted in a sustained mortality reduction 160 throughout life (P < 0.0001). Similar effects were seen when mTor was knocked down continuously. 161The red dotted line now indicated when mTor in the transient treatment is back to control levels. 162These experiments were all ran together at the same time but are split in two panels for graphical 163 purposes. 342

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Section: Resultsmentioning

confidence: 99%

Age-dependent effects of reduced mTor signalling on life expectancy through distinct physiology

Simons

Hartshorne

Trooster

et al. 2019

Preprint

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“…Researches demonstrated that during the aging, RC function is compromised which might be due to a high level of accumulated ROS from altered metabolic process and weakened antioxidant defense. However, the induction of mitohormesis to prevent age-related diseases at young age and manipulation of RC activity to prolong lifespan in latelife through pharmaceutics will be a promising avenue to pursue (Bouska et al, 2019).…”

Section: Mitochondrial Rosmentioning

confidence: 99%

Aging - Oxidative stress, antioxidants and computational modeling

Warraich

Hussain

Kayani

2020

Heliyon

134

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Aging is a degenerative, biological, time-dependent, universally conserved process thus designed as one of the highest known risk factors for morbidity and mortality. Every individual has its own aging mechanisms as both environmental conditions (75%) and genetics (25%) account for aging. Several theories have been proposed until now but not even a single theory solves this mystery. There are still some queries un-answered to the scientific community regarding mechanisms behind aging. However, oxidative stress theory (OST) is considered one of the famous theories that sees mitochondria as one of the leading organelles which largely contribute to the aging process. Many reactive oxygen species (ROS) are produced endogenously and exogenously that are associated with aging. But the mitochondrial ROS contribute largely to the aging process as mitochondrial dysfunction due to oxidative stress is considered one of the contributors toward aging. Although ROS is known to damage cell machinery, new evidence suggests their role in signal transduction to regulate biological and physiological processes. Moreover, besides mitochondria, other important cell organelles such as peroxisome and endoplasmic reticulum also produce ROS that contribute to aging. However, nature has provided humans with free radical scavengers called antioxidants that protect from harmful effects of ROS. Future predictions regarding aging, biochemical mechanisms involved, biomarkers internal and external factors can be easily done with machine learning algorithms and other computational models. This review explains important aspects of aging, the contribution of ROS producing organelles in aging, importance of antioxidants fighting against ROS, different computational models developed to understand the complexities of the aging.

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“…From their biosynthesis to their trafficking and degradation, proteins are controlled through different mechanisms including molecular chaperone networks and the ubiquitin-proteasome system (UPS) in the ER (3,13,18). The functioning of these mechanisms has been shown to be impaired with age in different organs including skin, liver, heart, brain, spleen, and lung (3,19,20). In the ER, chaperones such as calnexin, calreticulin, and binding immunoglobulin protein (BiP) [also known as glucose-regulated protein-78 (GRP78)] recognize and bind nascent and misfolded proteins to prevent their aggregation (21,22).…”

Section: Er Stress and Relation With Agementioning

confidence: 99%

“…However, over 90% of misfolded and damaged proteins are cleared through the UPS, which is a highly selective process as it degrades exclusively ubiquitinated proteins (13). As the protein quality control network of the cell, the UPS is crucial for the degradation of misfolded or unfolded and damaged proteins (19,29). However, this mechanism becomes impaired with age (13).…”

Section: Er Stress and Relation With Agementioning

confidence: 99%

The Stress of Lung Aging: Endoplasmic Reticulum and Senescence Tête-à-Tête

et al. 2021

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Beyond the structural changes, features including the dysregulation of endoplasmic reticulum (ER) stress response and increased senescence characterize the lung aging. ER stress response and senescence have been reported to be induced by factors like cigarette smoke. Therefore, deciphering the mechanisms underlying ER and senescent pathways interaction has become a challenge. In this review we highlight the known and unknown regarding ER stress response and senescence and their cross talk in aged lung.

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Organelle aging: Lessons from model organisms

Cited by 15 publications

References 202 publications

Age-dependent effects of reduced mTor signalling on life expectancy through distinct physiology

Age-dependent effects of reduced mTor signalling on life expectancy through distinct physiology

Aging - Oxidative stress, antioxidants and computational modeling

The Stress of Lung Aging: Endoplasmic Reticulum and Senescence Tête-à-Tête

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