DAF-16/FOXO and HLH-30/TFEB comprise a cooperative regulatory axis controlling tubular lysosome induction in C. elegans.

Although life expectancy has increased, longer lifespans do not always align with prolonged healthspans and, as a result, the occurrence of age-related degenerative diseases continues to increase. Thus, biomedical research has been shifting focus to strategies that enhance both lifespan and healthspan concurrently. Two major transcription factors that have been heavily studied in the context of aging and longevity are DAF-16/FOXO and HLH-30/TFEB; however, how these two factors coordinate to promote longevity is still not fully understood.

Restricting bioenergetic efficiency enhances longevity and mitochondrial redox capacity in Drosophila melanogaster.

Mitochondria are essential for survival and as such, impairments in organelle homeostasis significantly accelerate age-related morbidity and mortality. Here, we determined the contribution of bioenergetic efficiency to life span and health span in Drosophila melanogaster utilizing the mitochondrial uncoupler BAM15. Life span was determined in flies fed a normal diet (ND) or high fat diet (HFD) supplemented with vehicle or BAM15.

VCP promotes tTAF-target gene expression and spermatocyte differentiation by downregulating mono-ubiquitylated H2A.

Valosin-containing protein (VCP) binds and extracts ubiquitylated cargo to regulate protein homeostasis. VCP has been studied primarily in aging and disease contexts, but it also affects germline development. However, the precise molecular functions of VCP in the germline, particularly in males, are poorly understood.

A familial natural short sleep mutation promotes healthy aging and extends lifespan in .

Sleep loss typically imposes negative effects on animal health. However, humans with a rare genetic mutation in the gene () present an exception; these individuals sleep less without the usual effects associated with sleep deprivation. Thus, it has been suggested that the mutation activates compensatory mechanisms that allows these individuals to thrive with less sleep.

A familial natural short sleep mutation promotes healthy aging and extends lifespan in .

Sleep loss typically imposes negative effects on animal health. However, humans with a rare genetic mutation in the gene ( ) present an exception; these individuals sleep less without the usual effects associated with sleep deprivation. Thus, it has been suggested that the mutation activates compensatory mechanisms that allows these individuals to thrive with less sleep.

A meiotic switch in lysosome activity supports spermatocyte development in young flies but collapses with age.

Gamete development ultimately influences animal fertility. Identifying mechanisms that direct gametogenesis, and how they deteriorate with age, may inform ways to combat infertility. Recently, we found that lysosomes acidify during oocyte maturation in , suggesting that a meiotic switch in lysosome activity promotes female germ-cell health.

CRISPR/Cas9-engineered Drosophila knock-in models to study VCP diseases.

Mutations in Valosin Containing Protein (VCP) are associated with several degenerative diseases, including multisystem proteinopathy (MSP-1) and amyotrophic lateral sclerosis. However, patients with VCP mutations vary widely in their pathology and clinical penetrance, making it difficult to devise effective treatment strategies. A deeper understanding of how each mutation affects VCP function could enhance the prediction of clinical outcomes and design of personalized treatment options.

Examination of carnitine palmitoyltransferase 1 abundance in white adipose tissue: implications in obesity research.

Carnitine palmitoyltransferase 1 (CPT1) is essential for the transport of long-chain fatty acids into the mitochondria for oxidation. Recently, it was reported that decreased CPT1b mRNA in adipose tissue was a contributing factor for obesity in rats. We therefore closely examined the expression level of in adipose tissue from mice, rats, and humans.

Adenovirus 36 antibody detection: Improving the standard serum neutralization assay.

Adenovirus 36 (AdV36) causes weight gain in animal models, including non-human primates. In humans, AdV36-neutralizing antibodies are associated with adiposity; however, longitudinal studies in large populations are needed to clarify AdV36's contribution. The current gold standard for detection of AdV36-specific antibody is the serum neutralization assay (SNA), which requires long incubation times and highly trained personnel.

E4orf1 Enhances Glucose Uptake Independent of Proximal Insulin Signaling.

Impaired proximal insulin signaling is often present in diabetes. Hence, approaches to enhance glucose disposal independent of proximal insulin signaling are desirable. Evidence indicates that Adenovirus-derived E4orf1 protein may offer such an approach.

Impaired Mitochondrial Fat Oxidation Induces FGF21 in Muscle.

Fatty acids are the primary fuel source for skeletal muscle during most of our daily activities, and impaired fatty acid oxidation (FAO) is associated with insulin resistance. We have developed a mouse model of impaired FAO by deleting carnitine palmitoyltransferase-1b specifically in skeletal muscle (Cpt1b(m-/-)). Cpt1b(m-/-) mice have increased glucose utilization and are resistant to diet-induced obesity.

An adenovirus-derived protein: A novel candidate for anti-diabetic drug development.

Aims: Exposure to human adenovirus Ad36 is causatively and correlatively linked with better glycemic control in animals and humans, respectively. Although the anti-hyperglycemic property of Ad36 may offer some therapeutic potential, it is impractical to use an infectious agent for therapeutic benefit. Cell-based studies identified that Ad36 enhances cellular glucose disposal via its E4orf1 protein.

Human adenovirus Ad36 and its E4orf1 gene enhance cellular glucose uptake even in the presence of inflammatory cytokines.

Background: Aging and obesity are associated with elevated pro-inflammatory cytokines such as monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)α, which are linked to insulin resistance. Anti-inflammatory agents have marginal effect in improving insulin resistance. Hence, agents are needed to improve glycemic control despite the inflammation.

Accurate identification of neutralizing antibodies to adenovirus Ad36, -a putative contributor of obesity in humans.

Background: In children and adults, human adenovirus serotype 36 (Ad36) is linked with increased adiposity, and important metabolic alterations. Since this property is not shared by many other human adenovirus serotypes, it is imperative to specifically identify exposure to Ad36. Although serum neutralization assay (SNA) is the gold standard to specifically detect neutralizing antibodies (NA) to Ad36, it requires 2-weeks to complete and considerable training to interpret the results.

An observational study of the association between adenovirus 36 antibody status and weight loss among youth.

Objective: Although the human adenovirus 36 (Ad-36) is associated with obesity and relative hypolipidemia, its role in pediatric weight loss treatment response is uncertain. Therefore, the primary study objective was to determine whether Ad-36 antibody (AB) status was associated with response to a pediatric weight loss program. The secondary objective was to assess the association between Ad-36 AB status and baseline lipid values.

Doxycycline-regulated 3T3-L1 preadipocyte cell line with inducible, stable expression of adenoviral E4orf1 gene: a cell model to study insulin-independent glucose disposal.

Impaired glycemic control and excessive adiposity are major risk factors for Type 2 Diabetes mellitus. In rodent models, Ad36, a human adenovirus, improves glycemic control, independent of dietary fat intake or adiposity. It is impractical to use Ad36 for therapeutic action.

Long-term changes in adiposity and glycemic control are associated with past adenovirus infection.

Objective: Ad36, a human adenovirus, increases adiposity but improves glycemic control in animal models. Similarly, natural Ad36 infection is cross-sectionally associated with greater adiposity and better glycemic control in humans. This study compared longitudinal observations in indices of adiposity (BMI and body fat percentage) and glycemic control (fasting glucose and insulin) in Ad36-infected versus uninfected adults.

E4orf1 improves lipid and glucose metabolism in hepatocytes: a template to improve steatosis & hyperglycemia.

Hepatic steatosis often accompanies obesity and insulin resistance. The cornerstones of steatosis treatment include reducing body weight and dietary fat intake, which are marginally successful over the long term. Ad36, a human adenovirus, may offer a template to overcome these limitations.

E4orf1: a novel ligand that improves glucose disposal in cell culture.

Reducing dietary fat intake and excess adiposity, the cornerstones of behavioral treatment of insulin resistance (IR), are marginally successful over the long term. Ad36, a human adenovirus, offers a template to improve IR, independent of dietary fat intake or adiposity. Ad36 increases cellular glucose uptake via a Ras-mediated activation of phosphatidyl inositol 3-kinase(PI3K), and improves hyperglycemia in mice, despite a high-fat diet and without reducing adiposity.

PPARgamma-independent increase in glucose uptake and adiponectin abundance in fat cells.

Although thiazolidinediones (TZD) effectively improve hyperglycemia and increase adiponectin, a proinsulin-sensitizing adipokine, they also increase adipogenesis via peroxisome proliferator-activated receptor (PPAR)γ induction, which may be undesirable. Recent safety concerns about some TZD have prompted the search for next generation agents that can enhance glycemic control and adiponectin independent of PPARγ or adipogenesis. Reminiscent of TZD action, a human adenovirus, adenovirus 36 (Ad36), up-regulates PPARγ, induces adipogenesis, and improves systemic glycemic control in vivo.

Efficacy of low-level laser therapy for body contouring and spot fat reduction.

Background: Low-level laser therapy (LLLT) is commonly used in medical applications, but scientific studies of its efficacy and the mechanism by which it causes loss of fat from fat cells for body contouring are lacking. This study examined the effectiveness and mechanism by which 635–680 nm LLLT acts as a non-invasive body contouring intervention method.

Methods: Forty healthy men and women ages 18–65 years with a BMI <30 kg/m2 were randomized 1:1 to laser or control treatment.

Metabolically favorable remodeling of human adipose tissue by human adenovirus type 36.

Objective: Experimental infection of rats with human adenovirus type 36 (Ad-36) promotes adipogenesis and improves insulin sensitivity in a manner reminiscent of the pharmacologic effect of thiozolinediones. To exploit the potential of the viral proteins as a therapeutic target for treating insulin resistance, this study investigated the ability of Ad-36 to induce metabolically favorable changes in human adipose tissue.

Research Design And Methods: We determined whether Ad-36 increases glucose uptake in human adipose tissue explants.