Extended lifespan in female Drosophila melanogaster through late-life calorie restriction.

Calorie restriction has many beneficial effects on healthspan and lifespan in a variety of species. However, how late in life application of caloric restriction can extend fly life is not clear. Here we show that late-life calorie restriction increases lifespan in female Drosophila melanogaster aged on a high-calorie diet.

SIRT1, resveratrol and aging.

Aging is linked to a time-associated decline in both cellular function and repair capacity leading to malfunction on an organismal level, increased frailty, higher incidence of diseases, and death. As the population grows older, there is a need to reveal mechanisms associated with aging that could spearhead treatments to postpone the onset of age-associated decline, extend both healthspan and lifespan. One possibility is targeting the sirtuin SIRT1, the founding member of the sirtuin family, a highly conserved family of histone deacetylases that have been linked to metabolism, stress response, protein synthesis, genomic instability, neurodegeneration, DNA damage repair, and inflammation.

Late-life shift in caloric intake affects fly metabolism and longevity.

The prevalence of obesity is increasing in older adults and contributes to age-related decline. Caloric restriction (CR) alleviates obesity phenotypes and delays the onset of age-related changes. However, how late in life organisms benefit from switching from a high-(H) to a low-calorie (L) diet is unclear.

INDY-From Flies to Worms, Mice, Rats, Non-Human Primates, and Humans.

is a fly homologue of the mammalian SLC13A5 (mSLC13A5) plasma membrane citrate transporter, a key metabolic regulator and energy sensor involved in health, longevity, and disease. Reduction of gene activity in flies, and its homologs in worms, modulates metabolism and extends longevity. The metabolic changes are similar to what is obtained with caloric restriction (dietary restriction).

The Role of Citrate Transporter INDY in Metabolism and Stem Cell Homeostasis.

() is a fly gene that encodes a homologue of mammalian SLC13A5 plasma membrane citrate transporter. Reducing expression of gene in flies, and its homologues in worms, extends longevity. reduction in flies, worms, mice and rats affects metabolism by regulating the levels of cytoplasmic citrate, inducing a state similar to calorie restriction.

Evolution, Chance, and Aging.

Aging has provided fruitful challenges for evolutionary theory, and evolutionary theory has deepened our understanding of aging. A great deal of genetic and molecular data now exists concerning mortality regulation and there is a growing body of knowledge concerning the life histories of diverse species. Assimilating all relevant data into a framework for the evolution of aging promises to significantly advance the field.

The screening and evaluation of potential clinically significant HIV drug combinations against the SARS-CoV-2 virus.

Spike glycoprotein is essential for the reproduction of the SARS-CoV-2 virus, and its inhibition using already approved antiviral drugs may open new avenues for treatment of patients with the COVID-19 disease. Because of that we analyzed the inhibition of SARS-CoV-2 spike glycoprotein with FDA-approved antiviral drugs and their double and triple combinations. We used the VINI in silico model of cancer to perform this virtual drug screening, showing HIV drugs to be the most effective.

INDY-A New Link to Metabolic Regulation in Animals and Humans.

The () gene encodes the fly homolog of the mammalian SLC13A5 citrate transporter. Reduced expression of the gene in flies and worms extends their longevity. INDY is expressed in the plasma membrane of metabolically active tissues.

The effects of reduced levels on fly physiology.

Rpd3 is a conserved histone deacetylase that removes acetyl groups from lysine residues within histones and other proteins. Reduction or inhibition of Rpd3 extends longevity in yeast, worms, and flies. Previous studies in flies suggest an overlap with the mechanism of lifespan extension by dietary restriction.

interacts with insulin signaling in longevity extension.

Histone deacetylase (HDAC) 1 regulates chromatin compaction and gene expression by removing acetyl groups from lysine residues within histones. HDAC1 affects a variety of processes including proliferation, development, metabolism, and cancer. Reduction or inhibition of Rpd3, yeast and fly HDAC1 orthologue, extends longevity.

The effects of Rpd3 on fly metabolism, health, and longevity.

The epigenetic regulation of DNA structure and function is essential for changes in gene expression involved in development, growth, and maintenance of cellular function. Epigenetic changes include histone modifications such as methylation, acetylation, ubiquitination, and phosphorylation. Histone deacetylase (HDAC) proteins have a major role in epigenetic regulation of chromatin structure.

RPD3 histone deacetylase and nutrition have distinct but interacting effects on Drosophila longevity.

Single-gene mutations that extend longevity have revealed regulatory pathways related to aging and longevity. RPD3 is a conserved histone deacetylase (Class I HDAC). Previously we showed that Drosophila rpd3 mutations increase longevity.

The role of INDY in metabolism, health and longevity.

Indy (I'm Not Dead Yet) encodes the fly homolog of a mammalian SLC13A5 plasma membrane transporter. INDY is expressed in metabolically active tissues functioning as a transporter of Krebs cycle intermediates with the highest affinity for citrate. Decreased expression of the Indy gene extends longevity in Drosophila and C.

The first international mini-symposium on methionine restriction and lifespan.

It has been 20 years since the Orentreich Foundation for the Advancement of Science, under the leadership Dr. Norman Orentreich, first reported that low methionine (Met) ingestion by rats extends lifespan (Orentreich et al., 1993).

Increased mitochondrial biogenesis preserves intestinal stem cell homeostasis and contributes to longevity in Indy mutant flies.

The Drosophila Indy (I'm Not Dead Yet) gene encodes a plasma membrane transporter of Krebs cycle intermediates, with robust expression in tissues associated with metabolism. Reduced INDY alters metabolism and extends longevity in a manner similar to caloric restriction (CR); however, little is known about the tissue specific physiological effects of INDY reduction. Here we focused on the effects of INDY reduction in the Drosophila midgut due to the importance of intestinal tissue homeostasis in healthy aging and longevity.

Determination of the spontaneous locomotor activity in Drosophila melanogaster.

Drosophila melanogaster has been used as an excellent model organism to study environmental and genetic manipulations that affect behavior. One such behavior is spontaneous locomotor activity. Here we describe our protocol that utilizes Drosophila population monitors and a tracking system that allows continuous monitoring of the spontaneous locomotor activity of flies for several days at a time.

Indy mutations and Drosophila longevity.

Decreased expression of the fly and worm Indy genes extends longevity. The fly Indy gene and its mammalian homolog are transporters of Krebs cycle intermediates, with the highest rate of uptake for citrate. Cytosolic citrate has a role in energy regulation by affecting fatty acid synthesis and glycolysis.

Effect of sodium channel abundance on Drosophila development, reproductive capacity and aging.

The voltage-gated Na (+) channels (VGSC) are complex membrane proteins responsible for generation and propagation of the electrical signals through the brain, the skeletal muscle and the heart. The levels of sodium channels affect behavior and physical activity. This is illustrated by the maleless mutant allele (mle (napts)) in Drosophila, where the decreased levels of voltage-gated Na(+) channels cause temperature-sensitive paralysis.

Indy mutants: live long and prosper.

Indy encodes the fly homolog of a mammalian transporter of di and tricarboxylate components of the Krebs cycle. Reduced expression of fly Indy or two of the C. elegans Indy homologs leads to an increase in life span.