https://www.cell.com/cell/pdf/S0092-8674%2815%2900186-5.pdf

Promoting Health and Longevity through Diet: From Model Organisms to Humans

https://pure.mpg.de/pubman/item/item_3223707_1/component/file_3223708/O%20Sullivan%20et%20al..pdf

Memory CD8+ T cells use cell intrinsic lipolysis to support the metabolic programming necessary for development

Autophagy is a conserved process that catabolizes intracellular components to maintain energy homeostasis and to protect cells against stress. Autophagy has crucial roles during development and disease, and evidence accumulated over the past decade indicates that autophagy also has a direct role in modulating ageing. In particular, elegant studies using yeasts, worms, flies and mice have demonstrated a broad requirement for autophagy-related genes in the lifespan extension observed in a number of conserved longevity paradigms. Moreover, several new and interesting concepts relevant to autophagy and its role in modulating longevity have emerged. First, select tissues may require or benefit from autophagy activation in longevity paradigms, as tissue-specific overexpression of single autophagy genes is sufficient to extend lifespan. Second, selective types of autophagy may be crucial for longevity by specifically targeting dysfunctional cellular components and preventing their accumulation. And third, autophagy can influence organismal health and ageing even non-cell autonomously, and thus, autophagy stimulation in select tissues can have beneficial, systemic effects on lifespan. Understanding these mechanisms will be important for the development of approaches to improve human healthspan that are based on the modulation of autophagy.

Autophagy as a promoter of longevity: insights from model organisms

The C. elegans insulin/IGF-1 signaling (IIS) pathway connects nutrient levels to metabolism, growth, development, longevity, and behavior. This fundamental pathway is regulated by insulin-like peptide ligands that bind to the insulin/IGF-1 transmembrane receptor (IGFR) ortholog DAF-2. DAF-2/IGFR controls the activity of a conserved phosphoinositide 3-kinase (PI3K)/Akt kinase cascade, culminating in the regulation of a FoxO transcription factor, DAF-16, that governs most of the functions of this pathway. In light of the evolutionary conservation of the IIS pathway, its study in C. elegans is likely to shed light on its functions and regulation in higher organisms, including humans. Originally identified based on its role in the regulation of larval development and aging, IIS also controls a host of other biological processes. Here we review what is currently known about the biological functions and the molecular components of C. elegans IIS.

/pdf/insulin-insulin-like-growth-factor-signaling-in-c-elegans-6xzanar50d.pdf

Insulin/insulin-like growth factor signaling in C. elegans.

SKN-1/Nrf, stress responses, and aging in Caenorhabditis elegans.

https://www.cell.com/cell-metabolism/pdf/S1550-4131(12)00494-9.pdf

Reproduction, Fat Metabolism, and Life Span: What Is the Connection?

Background 
Preventing germline stem cell proliferation extends lifespan in nematodes and flies. So far, studies on germline-longevity signaling have focused on daf-16/FOXO and daf-12/VDR. Here, we report on NHR-80/HNF4, a nuclear receptor that specifically mediates longevity induced by depletion of the germ line through a mechanism that implicates fatty acid monodesaturation.


Methods and Findings 
nhr-80/HNF4 is induced in animals lacking a germ line and is specifically required for their extended longevity. Overexpressing nhr-80/HNF4 increases the lifespan of germline-less animals. This lifespan extension can occur in the absence of daf-16/FOXO but requires the presence of the nuclear receptor DAF-12/VDR. We show that the fatty acid desaturase, FAT-6/SCD1, is a key target of NHR-80/HNF4 and promotes germline-longevity by desaturating stearic acid to oleic acid (OA). We find that NHR-80/HNF4 and OA must work in concert to promote longevity.


Conclusions 
Taken together, our data indicate that the NHR-80 pathway participates in the mechanism of longevity extension through depletion of the germ line. We identify fat-6 and OA as essential downstream elements although other targets must also be present. Thus, NHR-80 links fatty acid desaturation to lifespan extension through germline ablation in a daf-16/FOXO independent manner.

/pdf/fatty-acid-desaturation-links-germ-cell-loss-to-longevity-17r0i30k0j.pdf

Fatty Acid Desaturation Links Germ Cell Loss to Longevity Through NHR-80/HNF4 in C. elegans

https://www.cell.com/cell-reports/pdf/S2211-1247(13)00680-3.pdf

Aging yeast cells undergo a sharp entry into senescence unrelated to the loss of mitochondrial membrane potential.

Dietary restriction (DR) increases healthspan and longevity in many species, including primates, but it is often accompanied by impaired reproductive function. Whether signals associated with the reproductive system contribute to or are required for DR effects on lifespan has not been established. Here we show that expression of the cytochrome P450 DAF-9/CYP450 and production of the steroid hormone Δ(7)-dafachronic acid (DA) are increased in C. elegans subjected to DR. DA signalling through the non-canonical nuclear hormone receptor NHR-8/NHR and the nutrient-responsive kinase let-363/mTOR is essential for DR-mediated longevity. Steroid signalling also affects germline plasticity in response to nutrient deprivation and this is required to achieve lifespan extension. These data demonstrate that steroid signalling links germline physiology to lifespan when nutrients are limited, and establish a central role for let-363/mTOR in integrating signals derived from nutrients and steroid hormones.

/pdf/steroid-hormone-signalling-links-reproduction-to-lifespan-in-rc5mmdw70o.pdf

Steroid hormone signalling links reproduction to lifespan in dietary-restricted Caenorhabditis elegans

Aging's most obvious characteristic is the time dependent increase of an individual's probability to die. This lifelong process is accompanied by a large number of molecular and physiological changes. Although numerous genes involved in aging have been identified in the past decades its leading factors have yet to be determined. To identify the very processes driving aging we have developed in the past years an assay to identify physiologically old individuals in a synchronized population of Drosophila melanogaster. Those individuals show an age-dependent increase of intestinal permeability followed by a high risk of death. Here we show that this physiological marker of aging is conserved in 3 invertebrate species Drosophila mojavensis, Drosophila virilis, Caenorhabditis elegans as well as in 1 vertebrate species Danio rerio. Our findings suggest that intestinal barrier dysfunction may be an important event in the aging process conserved across a broad range of species, thus raising the possibility that it may also be the case in Homo sapiens.

https://hal.archives-ouvertes.fr/hal-01304283/document

Hugo Aguilaniu

Papers

Reproduction, Fat Metabolism, and Life Span: What Is the Connection?

Fatty Acid Desaturation Links Germ Cell Loss to Longevity Through NHR-80/HNF4 in C. elegans

Aging yeast cells undergo a sharp entry into senescence unrelated to the loss of mitochondrial membrane potential.

Steroid hormone signalling links reproduction to lifespan in dietary-restricted Caenorhabditis elegans

Two phases of aging separated by the Smurf transition as a public path to death.