Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction without Extending Life Span

Transposable elements (TEs) are mobile genetic elements, highly enriched in heterochromatin, that constitute a large percentage of the DNA content of eukaryotic genomes. Aging in Drosophila melanogaster is characterized by loss of repressive heterochromatin structure and loss of silencing of reporter genes in constitutive heterochromatin regions. Using next-generation sequencing, we found that transcripts of many genes native to heterochromatic regions and TEs increased with age in fly heads and fat bodies. A dietary restriction regimen, known to extend life span, repressed the age-related increased expression of genes located in heterochromatin, as well as TEs. We also observed a corresponding age-associated increase in TE transposition in fly fat body cells that was delayed by dietary restriction. Furthermore, we found that manipulating genes known to affect heterochromatin structure, including overexpression of Sir2, Su(var)3–9, and Dicer-2, as well as decreased expression of Adar, mitigated age-related increases in expression of TEs. Increasing expression of either Su(var)3–9 or Dicer-2 also led to an increase in life span. Mutation of Dicer-2 led to an increase in DNA double-strand breaks. Treatment with the reverse transcriptase inhibitor 3TC resulted in decreased TE transposition as well as increased life span in TE-sensitized Dicer-2 mutants. Together, these data support the retrotransposon theory of aging, which hypothesizes that epigenetically silenced TEs become deleteriously activated as cellular defense and surveillance mechanisms break down with age. Furthermore, interventions that maintain repressive heterochromatin and preserve TE silencing may prove key to preventing damage caused by TE activation and extending healthy life span.

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Dietary restriction improves proteostasis and increases life span through endoplasmic reticulum hormesis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1900055116 ◽

2019 ◽

Vol 116 (35) ◽

pp. 17383-17392 ◽

Cited By ~ 32

Author(s):

Latika Matai ◽

Gautam Chandra Sarkar ◽

Manish Chamoli ◽

Yasir Malik ◽

Shashi Shekhar Kumar ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Life Span ◽

Dietary Restriction ◽

Adult Life ◽

Dependent Manner ◽

Adult Life Span ◽

Unfolded Protein ◽

Age Related ◽

Protein Response ◽

Polyglutamine Aggregation

Unfolded protein response (UPR) of the endoplasmic reticulum (UPRER) helps maintain proteostasis in the cell. The ability to mount an effective UPRER to external stress (iUPRER) decreases with age and is linked to the pathophysiology of multiple age-related disorders. Here, we show that a transient pharmacological ER stress, imposed early in development on Caenorhabditis elegans, enhances proteostasis, prevents iUPRER decline with age, and increases adult life span. Importantly, dietary restriction (DR), that has a conserved positive effect on life span, employs this mechanism of ER hormesis for longevity assurance. We found that only the IRE-1–XBP-1 branch of UPRER is required for the longevity effects, resulting in increased ER-associated degradation (ERAD) gene expression and degradation of ER resident proteins during DR. Further, both ER hormesis and DR protect against polyglutamine aggregation in an IRE-1–dependent manner. We show that the DR-specific FOXA transcription factor PHA-4 transcriptionally regulates the genes required for ER homeostasis and is required for ER preconditioning-induced life span extension. Finally, we show that ER hormesis improves proteostasis and viability in a mammalian cellular model of neurodegenerative disease. Together, our study identifies a mechanism by which DR offers its benefits and opens the possibility of using ER-targeted pharmacological interventions to mimic the prolongevity effects of DR.

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Positive Emodiversity Buffers the Association Between Stress and Depressive Symptoms

Innovation in Aging ◽

10.1093/geroni/igaa057.2250 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 653-653

Author(s):

Lizbeth Benson ◽

Anthony Ong

Keyword(s):

Older Adults ◽

Depressive Symptoms ◽

Life Span ◽

Daily Diary ◽

National Study ◽

Younger Adults ◽

Shannon's Entropy ◽

Daily Experiences ◽

Age Related ◽

Optimal Functioning

Abstract Intensive measurements of individuals’ experiences allow for identifying patterns of functioning that may be markers of resilience, and whether such patterns differ across the life span. Using 8 daily diary reports collected in the second burst of the National Study of Daily Experiences (NSDE, n=848, age 34-84; 55%female), we examined whether positive emodiversity (Shannon’s entropy) attenuated the association between cumulative stressor exposure and depressive symptoms, and age-related differences therein. Results indicated age moderated the extent to which positive emodiversity attenuated the association between stress and depressive symptoms (b=0.11, p < .05). The attenuated association was strongest for younger adults with higher positive emodiversity, compared to those with lower positive emodiversity. For older adults, the association between stress and depressive symptoms was relatively similar regardless of their positive emodiversity. Implications pertain to for whom and in what contexts specific types of dynamic emotion experiences may promote optimal functioning and resilience.

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Dietary Restriction, Cardiovascular Aging and Age-Related Cardiovascular Diseases: A Review of the Evidence

Reviews on Biomarker Studies in Aging and Anti-Aging Research - Advances in Experimental Medicine and Biology ◽

10.1007/978-3-030-25650-0_7 ◽

2019 ◽

pp. 113-127 ◽

Cited By ~ 1

Author(s):

Behnaz Abiri ◽

Mohammadreza Vafa

Keyword(s):

Cardiovascular Diseases ◽

Dietary Restriction ◽

Age Related ◽

Cardiovascular Aging

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Monitoring Age-Related Changes in the Lactate/Pyruvate Ratio Using a Colorimetric Assay in a C. elegans Model of Increased Life Span

Methods in Molecular Biology - Pre-Clinical Models ◽

10.1007/978-1-4939-8994-2_12 ◽

2018 ◽

pp. 123-132 ◽

Cited By ~ 1

Author(s):

Sumino Yanase ◽

Kayo Yasuda ◽

Naoki Ishii

Keyword(s):

Life Span ◽

Colorimetric Assay ◽

C Elegans ◽

Age Related ◽

Age Related Changes ◽

Pyruvate Ratio

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Dietary restriction by bacterial deprivation increases life span in wild-derived nematodes

Experimental Gerontology ◽

10.1016/j.exger.2007.10.019 ◽

2008 ◽

Vol 43 (3) ◽

pp. 130-135 ◽

Cited By ~ 47

Author(s):

George L. Sutphin ◽

Matt Kaeberlein

Keyword(s):

Life Span ◽

Dietary Restriction

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The genetic paradigms of dietary restriction fail to extend life span in cep-1(gk138) mutant of C. elegans p53 due to possible background mutations

10.1101/2020.07.09.195503 ◽

2020 ◽

Author(s):

Anita Goyala ◽

Aiswarya Baruah ◽

Arnab Mukhopadhyay

Keyword(s):

Life Span ◽

Dietary Restriction ◽

Model Systems ◽

Regulation Of Expression ◽

Life Span Extension ◽

Phenotypic Differences ◽

C Elegans ◽

Xenobiotic Detoxification ◽

Organismal Biology ◽

Extend Life Span

AbstractDietary restriction (DR) increases life span and improves health in most model systems tested, including non-human primates. In C. elegans, as in other models, DR leads to reprogramming of metabolism, improvements in mitochondrial health, large changes in gene expression, including increase in expression of cytoprotective genes, better proteostasis etc. Understandably, multiple global transcriptional regulators like transcription factors FOXO/DAF-16, FOXA/PHA-4, HSF1/HSF-1 and NRF2/SKN-1 are important for DR longevity. Considering the wide-ranging effects of p53 on organismal biology, we asked whether the C. elegans ortholog, CEP-1 is required for DR-mediated longevity assurance. We employed the widely-used TJ1 strain of cep-1(gk138). We show that cep-1(gk138) suppresses the life span extension of two genetic paradigms of DR, but two non-genetic modes of DR remain unaffected in this strain. We find that in cep-1(gk138), two aspects of DR, increased autophagy and the up-regulation of expression of cytoprotective xenobiotic detoxification program (cXDP) genes are dampened. Importantly, we find that background mutation(s) in the strain may be the actual cause for the phenotypic differences that we observed and cep-1 may not be directly involved in genetic DR-mediated longevity assurance in worms. Identifying these mutation(s) may reveal a novel regulator of longevity required specifically by genetic modes of DR.

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