Hexokinase regulates Mondo-mediated longevity via the PPP and organellar dynamics.

The transcriptional complex Mondo/Max-like, MML-1/MXL-2, acts as a convergent transcriptional regulatory output of multiple longevity pathways in . These transcription factors coordinate nutrient sensing with carbohydrate and lipid metabolism across the evolutionary spectrum. While most studies have focused on the downstream outputs, little is known about the upstream inputs that regulate these transcription factors in a live organism.

Mitochondrial translocation of TFEB regulates complex I and inflammation.

TFEB is a master regulator of autophagy, lysosome biogenesis, mitochondrial metabolism, and immunity that works primarily through transcription controlled by cytosol-to-nuclear translocation. Emerging data indicate additional regulatory interactions at the surface of organelles such as lysosomes. Here we show that TFEB has a non-transcriptional role in mitochondria, regulating the electron transport chain complex I to down-modulate inflammation.

Refeeding-associated AMPK complex activity is a hallmark of health and longevity.

Late-life-initiated dietary interventions show limited efficacy in extending longevity or mitigating frailty, yet the underlying causes remain unclear. Here we studied the age-related fasting response of the short-lived killifish Nothobranchius furzeri. Transcriptomic analysis uncovered the existence of a fasting-like transcriptional program in the adipose tissue of old fish that overrides the feeding response, setting the tissue in persistent metabolic quiescence.

A novel TNFRSF1A mutation associated with TNF-receptor-associated periodic syndrome and its metabolic signature.

Objective: We describe a family with a novel mutation in the TNF Receptor Superfamily Member 1A (TNFRSF1A) gene causing TNF receptor-associated periodic syndrome (TRAPS) with renal AA amyloidosis.

Methods: Case series of affected family members. We further investigated the plasma metabolome of these patients in comparison with healthy controls using mass spectrometry.

miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact proteotoxicity and muscle function during aging.

Muscle function relies on the precise architecture of dynamic contractile elements, which must be fine-tuned to maintain motility throughout life. Muscle is also plastic, and remodeled in response to stress, growth, neural and metabolic inputs. The conserved muscle-enriched microRNA, miR-1, regulates distinct aspects of muscle development, but whether it plays a role during aging is unknown.

NFYB-1 regulates mitochondrial function and longevity via lysosomal prosaposin.

Mitochondria are multidimensional organelles whose activities are essential to cellular vitality and organismal longevity, yet underlying regulatory mechanisms spanning these different levels of organization remain elusive. Here we show that Caenorhabditis elegans nuclear transcription factor Y, beta subunit (NFYB-1), a subunit of the NF-Y transcriptional complex, is a crucial regulator of mitochondrial function. Identified in RNA interference (RNAi) screens, NFYB-1 loss leads to perturbed mitochondrial gene expression, reduced oxygen consumption, mitochondrial fragmentation, disruption of mitochondrial stress pathways, decreased mitochondrial cardiolipin levels and abolition of organismal longevity triggered by mitochondrial impairment.

Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling.

Mitochondrial network remodeling between fused and fragmented states facilitates mitophagy, interaction with other organelles, and metabolic flexibility. Aging is associated with a loss of mitochondrial network homeostasis, but cellular processes causally linking these changes to organismal senescence remain unclear. Here, we show that AMP-activated protein kinase (AMPK) and dietary restriction (DR) promote longevity in C.

Slm35 links mitochondrial stress response and longevity through TOR signaling pathway.

In most eukaryotic cells mitochondria are essential organelles involved in a great variety of cellular functions. One of the physiological processes linked to mitochondria is aging, a gradual process of damage accumulation that eventually promotes cell death. Aging depends on a balance between mitochondrial biogenesis, function and degradation.