The Genetic Architecture of Longevity

Arking, Robert

doi:10.1007/978-1-60327-507-1_4

Cited by 5 publications

(3 citation statements)

References 38 publications

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“…Analysis of these life stages in model organisms showed that they are characterized by different patterns of gene expression such that the health span is defined by tightly regulated gene expression which maximizes tissue function while minimizing inflammatory and other damage responses; the transition phase is characterized by a qualitative decrease in the regulatory ability of the cell, and the senescent span is characterized by a stochastic pattern of degradation of the gene expression network (Arking, 2009). …”

Section: Introductionmentioning

confidence: 99%

Chemical regulation of mid- and late-life longevities in Drosophila

McDonald

Maizi

Arking

2013

Experimental Gerontology

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We tested the effects of a Class I histone deacetylase inhibitor (HDAcI), sodium butyrate (NaBu), on the longevity of normal- and long-lived strains of Drosophila melanogaster. This HDAcI has mixed effects in the normal-lived Ra strain as it decreases mortality rates and increases longevity when administered in the transition or senescent spans, but decreases longevity when administered over the health span only or over the entire adult lifespan. Mostly deleterious effects are noted when administered by either method to the long-lived La strain. Thus “mid- to late-life” drugs may have different stage-specific effects on different genomes of a model organism. A different HDAcI (suberoylanilide hydroxamic acid, SAHA) administered to the normal-lived strain showed similar late-life extending effects, suggesting that this is not an isolated effect of one drug. These data also show that the use of an HDAcI can significantly alter the mortality rate of the senescent span by decreasing its vulnerability, or short-term risk of death, in a manner similar to that of dietary restriction. These studies may help to shed light on the frailty syndrome affecting some aging organisms.

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Section: Introductionmentioning

confidence: 99%

Chemical regulation of mid- and late-life longevities in Drosophila

McDonald

Maizi

Arking

2013

Experimental Gerontology

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“…In analysis conducted in different model organisms, it has been shown that these life stages are characterized by different gene expression patterns. The health span is characterized by a tightly regulated gene expression pattern which leads to a maximized tissue function and to a minimized inflammatory and other damage response; the transition phase is characterized by a gradual decline of the cellular regulatory capacity, and the senescent span is characterized by a gradual deregulation of the gene expression pattern (Arking 2009). In a recent study by McDonald et al (2013), a normal-lived Ra strain demonstrated a decreased mortality rate and an increased life span if it was administered with SB during transition or senescent spans, but a decreased life span when administered throughout the entire adult life span or health span only.…”

Section: Sodium Butyratementioning

confidence: 99%

Life Extension in Drosophila by Histone Deacetylase Inhibitors

Vaiserman

Pasyukova

2015

Life Extension

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In the last years, epigenetic regulatory mechanisms are increasingly appreciated as central to a diverse array of age-associated processes such as cellular and organismal senescence, genomic instability, and tumorigenesis. Recently, histone deacetylase inhibitors (HDACIs), a novel class of drugs targeting epigenetic pathways, have been proposed as a highly promising type of drugs with anti-aging effects. This chapter presents an overview of the anti-aging and lifeextending effects of HDACIs such as phenilbutyrate, sodium butyrate, trichistatin A and suberoylanilide hydroxamic acid as well as their plausible mechanism(s) of action in Drosophila melanogaster. Data supporting the hypothesis that life span extension induced by HDACIs may be caused by generalized changes in epigenetic regulation of gene expression are discussed. Overall, findings reviewed in this chapter suggest that uncovering which genetic factors and signaling pathways contributing to healthy aging can be influenced by HDACIs in fruit fly may facilitate the development of new strategies for treating and preventing age-related human diseases and health span extension.

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“…The adult life of Drosophila is categorized into health (no natural death occurs), transition (slight decline in the mortality curve showing 10% death), and senescence stage (steady decline in mortality curve represented by the window between the end of the transition phase till maximum life span of the fly) ( Arking et al, 2002 ). Analysis of these adult life stages in model organisms has revealed that they are characterized by different patterns of gene expression ( Pletcher et al, 2002 ; Arking, 2009 , 2015 ), which is similar to that of the equivalent life stages of humans. A transcriptomic analysis using microarrays to compare the gene expression profiles of different life stages of Drosophila melanogaster has identified 1,184 genes with pronounced differences in expression level between young and old age groups ( Bordet et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Adult health and transition stage-specific rotenone-mediated Drosophila model of Parkinson’s disease: Impact on late-onset neurodegenerative disease models

Ayajuddin

Phom

Koza

et al. 2022

Front. Mol. Neurosci.

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Parkinson’s disease (PD) affects almost 1% of the population worldwide over the age of 50 years. Exposure to environmental toxins like paraquat and rotenone is a risk factor for sporadic PD which constitutes 95% of total cases. Herbicide rotenone has been shown to cause Parkinsonian symptoms in multiple animal models. Drosophila is an excellent model organism for studying neurodegenerative diseases (NDD) including PD. The aging process is characterized by differential expression of genes during different life stages. Hence it is necessary to develop life-stage-matched animal models for late-onset human disease(s) such as PD. Such animal models are critical for understanding the pathophysiology of age-related disease progression and important to understand if a genotropic drug/nutraceutical can be effective during late stages. With this idea, we developed an adult life stage-specific (health and transition phase, during which late-onset NDDs such as PD sets in) rotenone-mediated Drosophila model of idiopathic PD. Drosophila is susceptible to rotenone in dose-time dependent manner. Rotenone-mediated fly model of sporadic PD exhibits mobility defects (independent of mortality), inhibited mitochondrial complex I activity, dopaminergic (DAergic) neuronal dysfunction (no loss of DAergic neuronal number; however, reduction in rate-limiting enzyme tyrosine hydroxylase (TH) synthesis), and alteration in levels of dopamine (DA) and its metabolites; 3,4-Dihydroxyphenylacetic acid (DOPAC) and Homovanilic acid (HVA) in brain-specific fashion. These PD-linked behaviors and brain-specific phenotypes denote the robustness of the present fly model of PD. This novel model will be of great help to decipher life stage-specific genetic targets of small molecule mediated DAergic neuroprotection; understanding of which is critical for formulating therapeutic strategies for PD.

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The Genetic Architecture of Longevity

Cited by 5 publications

References 38 publications

Chemical regulation of mid- and late-life longevities in Drosophila

Chemical regulation of mid- and late-life longevities in Drosophila

Life Extension in Drosophila by Histone Deacetylase Inhibitors

Adult health and transition stage-specific rotenone-mediated Drosophila model of Parkinson’s disease: Impact on late-onset neurodegenerative disease models

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