Biological resilience and aging: Activation of stress response pathways contributes to lifespan extension

Soo, Sonja K.; Rudich, Zenith D.; Ko, Bokang; Moldakozhayev, Alibek; AlOkda, Abdelrahman; Raamsdonk, Jeremy M. Van

doi:10.1016/j.arr.2023.101941

Cited by 25 publications

(15 citation statements)

References 208 publications

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“…The treatment with DHA-TG specially enhanced the activity and expression of the SOD enzyme family. Since the effect of DHA-TG is lost in DAF-16 deficient strain, and the expression of sod-3 is very dependent on the factor DAF-16/FOXO [67], it might be hypothesized that healthspan-promoting effects of DHA-TG are closely related to the antioxidant response using DAF-16 as an intermediary, as stated in similar research [68,69].…”

Section: Discussionmentioning

confidence: 87%

Structured Docosahexaenoic Acid (DHA) Enhances Motility and Promotes the Antioxidant Capacity of Aged C. elegans

Mora,

Pérez-Santamaria,

Tortajada-Pérez

et al. 2023

Cells

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The human lifespan has increased over the past century; however, healthspans have not kept up with this trend, especially cognitive health. Among nutrients for brain function maintenance, long-chain omega-3 polyunsaturated fatty acids (ω-3 LCPUFA): DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) must be highlighted, particularly structured forms of EPA and DHA which were developed to improve bioavailability and bioactivity in comparison with conventional ω-3 supplements. This study aims to elucidate the effect of a structured triglyceride form of DHA (DHA-TG) on the healthspan of aged C. elegans. Using a thrashing assay, the nematodes were monitored at 4, 8, and 12 days of adulthood, and DHA-TG improved its motility at every age without affecting lifespan. In addition, the treatment promoted antioxidant capacity by enhancing the activity and expression of SOD (superoxide dismutase) in the nematodes. Lastly, as the effect of DHA-TG was lost in the DAF-16 mutant strain, it might be hypothesized that the effects of DHA need DAF-16/FOXO as an intermediary. In brief, DHA-TG exerted a healthspan-promoting effect resulting in both enhanced physical fitness and increased antioxidant defense in aged C. elegans. For the first time, an improvement in locomotive function in aged wild-type nematodes is described following DHA-TG treatment.

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Section: Discussionmentioning

confidence: 87%

Structured Docosahexaenoic Acid (DHA) Enhances Motility and Promotes the Antioxidant Capacity of Aged C. elegans

Mora,

Pérez-Santamaria,

Tortajada-Pérez

et al. 2023

Cells

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“…Activation of key pathways of cellular resilience such as the DAF-16-mediated stress response, the p38-mediated innate immune signaling pathway, the mitochondrial unfolded protein response, the cytosolic unfolded protein response, the SKN-1-mediated oxidative stress response and the HIF-1-mediated hypoxia response can enhance resistance to stress and contribute to lifespan extension [35, 36, 45–48]. To determine if activation of cellular resilience pathways contributes to the lifespan extension and stress resistance in the mitochondrial fission and fusion overexpression strains, we measured mRNA levels of target genes for each pathway using quantitative RT-PCR.…”

Section: Resultsmentioning

confidence: 99%

“…In C. elegans , inhibition of the mitochondrial fusion gene fzo-1 is reported to have no effect on lifespan, while inhibition of eat-3 may increase lifespan [33, 34]. Furthermore, we previously reported that disruption of either fzo-1 or eat-3 activates multiple stress response pathways that are known to be tightly linked with mechanisms of longevity extension, including the DAF-16-mediated stress response, the SKN-1-mediated oxidative stress response and the ATFS-1-mediated mitochondrial unfolded protein response [17, 35, 36].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of mitochondrial fusion genes enhances resilience and extends longevity

Traa,

Keil,

Rudich

et al. 2023

Preprint

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The dynamicity of the mitochondrial network is crucial for meeting the ever-changing metabolic and energy needs of the cell. Mitochondrial fission promotes the degradation and distribution of mitochondria, while mitochondrial fusion maintains mitochondrial function through the complementation of mitochondrial components. Previously, we have reported that mitochondrial networks are tubular, interconnected and well-organized in young, healthy C. elegans, but become fragmented and disorganized with advancing age and in models of age-associated neurodegenerative disease. In this work, we examine the effects of increasing mitochondrial fission or mitochondrial fusion capacity by ubiquitously overexpressing the mitochondrial fission gene drp-1 or the mitochondrial fusion genes fzo-1 and eat-3, individually or in combination. We then measured mitochondrial function, mitochondrial network morphology, physiologic rates, stress resistance and lifespan. Surprisingly, we found that overexpression of either mitochondrial fission or fusion machinery both resulted in an increase in mitochondrial fragmentation. Similarly, both mitochondrial fission and mitochondrial fusion overexpression strains have extended lifespans and increased stress resistance, which appears to be at least partially due to the upregulation of multiple stress response pathways in these strains. Overall, our work demonstrates that increasing the expression of mitochondrial fission or fusion genes extends lifespan and improves biological resilience without promoting the maintenance of a youthful mitochondrial network morphology. This work highlights the importance of the mitochondria for both resilience and longevity.

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“…The most commonly used mutants are temperature-sensitive and are subjected to the restrictive temperature during larval stages to induce their phenotype ( Arantes-Oliveira et al, 2002 ). Similar to the Z2/Z3-ablated animals, glp-1 mutant hermaphrodites are long-lived ( Hsin and Kenyon, 1999 ), display delayed senescent phenotypes ( Palikaras et al, 2017 ) and are stress-resistant ( Arantes-Oliveira et al, 2002 ; Miyata et al, 2008 ; Alper et al, 2010 ; Soo et al, 2023 ).…”

Section: Comparing Germline-ablated Animals and Germline-less Mutantsmentioning

confidence: 99%

“…These studies showed that single gene mutations can greatly extend C. elegans lifespan, sometimes up to tenfold compared to its normal lifespan ( Friedman and Johnson, 1988 ; Kenyon et al, 1993 ; Ayyadevara et al, 2008 ). Several pathways, including the highly conserved insulin signaling pathway and a germline signaling pathway ( Kenyon, 2011 ; Ghazi, 2013 ), are involved in modulating aging ( Soo et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Decoding lifespan secrets: the role of the gonad in Caenorhabditis elegans aging

Pires da Silva,

Kelleher,

Reynoldson

2024

Front. Aging

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The gonad has become a central organ for understanding aging in C. elegans, as removing the proliferating stem cells in the germline results in significant lifespan extension. Similarly, when starvation in late larval stages leads to the quiescence of germline stem cells the adult nematode enters reproductive diapause, associated with an extended lifespan. This review summarizes recent advancements in identifying the mechanisms behind gonad-mediated lifespan extension, including comparisons with other nematodes and the role of lipid signaling and transcriptional changes. Given that the gonad also mediates lifespan regulation in other invertebrates and vertebrates, elucidating the underlying mechanisms may help to gain new insights into the mechanisms and evolution of aging.

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Biological resilience and aging: Activation of stress response pathways contributes to lifespan extension

Cited by 25 publications

References 208 publications

Structured Docosahexaenoic Acid (DHA) Enhances Motility and Promotes the Antioxidant Capacity of Aged C. elegans

Structured Docosahexaenoic Acid (DHA) Enhances Motility and Promotes the Antioxidant Capacity of Aged C. elegans

Overexpression of mitochondrial fusion genes enhances resilience and extends longevity

Decoding lifespan secrets: the role of the gonad in Caenorhabditis elegans aging

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