From bugs to bedside: functional annotation of human genetic variation for neurological disorders using invertebrate models.

The exponential accumulation of DNA sequencing data has opened new avenues for discovering the causative roles of single-nucleotide polymorphisms (SNPs) in neurological diseases. The opportunities emerging from this are staggering, yet only as good as our abilities to glean insights from this surplus of information. Whereas computational biology continues to improve with respect to predictions and molecular modeling, the differences between in silico and in vivo analysis remain substantial.

Systemic RNA Interference Defective (SID) genes modulate dopaminergic neurodegeneration in C. elegans.

The fine-tuning of gene expression is critical for all cellular processes; aberrations in this activity can lead to pathology, and conversely, resilience. As their role in coordinating organismal responses to both internal and external factors have increasingly come into focus, small non-coding RNAs have emerged as an essential component to disease etiology. Using Systemic RNA interference Defective (SID) mutants of the nematode Caenorhabditis elegans, deficient in gene silencing, we examined the potential consequences of dysfunctional epigenomic regulation in the context of Parkinson's disease (PD).

Aging: What We Can Learn From Elephants.

Elephants are large-brained, social mammals with a long lifespan. Studies of elephants can provide insight into the aging process, which may be relevant to understanding diseases that affect elderly humans because of their shared characteristics that have arisen through independent evolution. Elephants become sexually mature at 12 to 14 years of age and are known to live into, and past, their 7 decade of life.

Scavenging mitochondrial hydrogen peroxide by peroxiredoxin 3 overexpression attenuates contractile dysfunction and muscle atrophy in a murine model of accelerated sarcopenia.

Age-related muscle atrophy and weakness, or sarcopenia, are significant contributors to compromised health and quality of life in the elderly. While the mechanisms driving this pathology are not fully defined, reactive oxygen species, neuromuscular junction (NMJ) disruption, and loss of innervation are important risk factors. The goal of this study is to determine the impact of mitochondrial hydrogen peroxide on neurogenic atrophy and contractile dysfunction.

French-fried potato consumption and energy balance: a randomized controlled trial.

Background: Epidemiologic observations suggest increased potato consumption correlates with weight gain, adiposity, and diabetes risk, whereas nut consumption is associated with weight control and metabolic health. Randomized controlled trial (RCT) data indicate humans respond to changes in energy intake in single dietary components and compensate for extra energy consumed.

Objectives: We completed an RCT testing whether increased daily potato consumption influences energy balance [specifically, fat mass (FM)] compared with calorie-matched almond consumption.

From Model Organisms to Humans, the Opportunity for More Rigor in Methodologic and Statistical Analysis, Design, and Interpretation of Aging and Senescence Research.

This review identifies frequent design and analysis errors in aging and senescence research and discusses best practices in study design, statistical methods, analyses, and interpretation. Recommendations are offered for how to avoid these problems. The following issues are addressed: (a) errors in randomization, (b) errors related to testing within-group instead of between-group differences, (c) failing to account for clustering, (d) failing to consider interference effects, (e) standardizing metrics of effect size, (f) maximum life-span testing, (g) testing for effects beyond the mean, (h) tests for power and sample size, (i) compression of morbidity versus survival curve squaring, and (j) other hot topics, including modeling high-dimensional data and complex relationships and assessing model assumptions and biases.

Angiotensin (1-7) Expressing Probiotic as a Potential Treatment for Dementia.

Increasing life expectancies are unfortunately accompanied by increased prevalence of Alzheimer's disease (AD). Regrettably, there are no current therapeutic options capable of preventing or treating AD. We review here data indicating that AD is accompanied by gut dysbiosis and impaired renin angiotensin system (RAS) function.

Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice.

Calorie restriction (CR) promotes healthy ageing in diverse species. Recently, it has been shown that fasting for a portion of each day has metabolic benefits and promotes lifespan. These findings complicate the interpretation of rodent CR studies, in which animals typically eat only once per day and rapidly consume their food, which collaterally imposes fasting.

Bridging the Gap: A Geroscience Primer for Neuroscientists With Potential Collaborative Applications.

While neurodegenerative diseases can strike at any age, the majority of afflicted individuals are diagnosed at older ages. Due to the important impact of age in disease diagnosis, the field of neuroscience could greatly benefit from the many of the theories and ideas from the biology of aging-now commonly referred as geroscience. As discussed in our complementary perspective on the topic, there is often a "silo-ing" between geroscientists who work on understanding the mechanisms underlying aging and neuroscientists who are studying neurodegenerative diseases.

A Neuroscience Primer for Integrating Geroscience With the Neurobiology of Aging.

Neuroscience has a rich history of studies focusing on neurobiology of aging. However, much of the aging studies in neuroscience occur outside of the gerosciences. The goal of this primer is 2-fold: first, to briefly highlight some of the history of aging neurobiology and second, to introduce to geroscientists the broad spectrum of methodological approaches neuroscientists use to study the neurobiology of aging.

Einstein-Nathan Shock Center: translating the hallmarks of aging to extend human health span.

The overarching mission of the Einstein-Nathan Shock Center (E-NSC) is to make scientific discoveries in geroscience, leveraging on the expertise in our center in 6 out of the 7 pillars of aging, and to translate their effects towards drug discovery. The relevance of this basic biology of aging discoveries to humans will be confirmed through the unique gero-human resource at E-NSC. This is achieved through services provided by E-NSC, connectivity among its members, attracting worldwide investigators, and providing them with the opportunities to become future leaders.

Forgot to Exercise? Exercise Derived Circulating Myokines in Alzheimer's Disease: A Perspective.

Regular exercise plays an essential role in maintaining healthy neurocognitive function and central nervous system (CNS) immuno-metabolism in the aging CNS. Physical activity decreases the risk of developing Alzheimer's Disease (AD), is associated with better AD prognosis, and positively affects cognitive function in AD patients. Skeletal muscle is an important secretory organ, communicating proteotoxic and metabolic stress to distant tissues, including the CNS, through the secretion of bioactive molecules collectively known as myokines.

Mechanisms of exercise as a preventative measure to muscle wasting.

Skeletal muscle is the most abundant tissue in healthy individuals and it has important roles in health beyond voluntary movement. The overall mass and energy requirements of skeletal muscle require it to be metabolically active and flexible to multiple energy substrates. The tissue has evolved to be largely load dependent and it readily adapts in a number of positive ways to repetitive overload, such as various forms of exercise training.

Rapamycin restores brain vasculature, metabolism, and blood-brain barrier in an inflammaging model.

Rapamycin (RAPA) is found to have neuro-protective properties in various neuroinflammatory pathologies, including brain aging. With magnetic resonance imaging (MRI) techniques, we investigated the effect of RAPA in a lipopolysaccharide (LPS)-induced inflammaging model in rat brains. Rats were exposed to saline (control), or LPS alone or LPS combined with RAPA treatment (via food over 6 weeks).

Conserved nicotine-activated neuroprotective pathways involve mitochondrial stress.

Tobacco smoking is a risk factor for several human diseases. Conversely, smoking also reduces the prevalence of Parkinson's disease, whose hallmark is degeneration of dopaminergic neurons (DNs). We use as a model to investigate whether tobacco-derived nicotine activates nicotinic acetylcholine receptors (nAChRs) to selectively protect DNs.

Cell-to-cell variation in gene expression and the aging process.

There is tremendous variation in biological traits, and much of it is not accounted for by variation in DNA sequence, including human diseases and lifespan. Emerging evidence points to differences in the execution of the genetic program as a key source of variation, be it stochastic variation or programmed variation. Here we discuss variation in gene expression as an intrinsic property and how it could contribute to variation in traits, including the rate of aging.

Adiposity, reproductive and metabolic health, and activity levels in zoo Asian elephant ().

Many captive Asian elephant populations are not self-sustaining, possibly due in part to obesity-related health and reproductive issues. This study investigated relationships between estimated body composition and metabolic function, inflammatory markers, ovarian activity (females only) and physical activity levels in 44 Asian elephants (=35 females, =9 males). Deuterium dilution was used to measure total body water from which fat mass (FM) and fat-free mass (FFM) could be derived to estimate body composition.

A cell-nonautonomous mechanism of yeast chronological aging regulated by caloric restriction and one-carbon metabolism.

Caloric restriction (CR) improves health span and life span of organisms ranging from yeast to mammals. Understanding the mechanisms involved will uncover future interventions for aging-associated diseases. In budding yeast, Saccharomyces cerevisiae, CR is commonly defined by reduced glucose in the growth medium, which extends both replicative and chronological life span (CLS).