Nutrition and Healthy Aging

Because every species has unique attributes relevant to understanding specific aspects of aging, using a diversity of study systems and a comparative biology approach for aging research has the potential to lead to novel discoveries applicable to human health. Monogonont rotifers, a standard model for studies of aquatic ecology, evolutionary biology, and ecotoxicology, have also been used to study lifespan and healthspan for nearly a century. However, because much of this work has been published in the ecology and evolutionary biology literature, it may not be known to the biomedical research community. In this review, we provide an overview of Brachionus rotifers as a model to investigate nutritional and metabolic regulators of aging, with a focus on recent studies of dietary and metabolic pathway manipulation. Rotifers are microscopic, aquatic invertebrates with many advantages as a system for studying aging, including a two-week lifespan, easy laboratory culture, direct development without a larval stage, sexual and asexual reproduction, easy delivery of pharmaceuticals in liquid culture, and transparency allowing imaging of cellular morphology and processes. Rotifers have greater gene homology with humans than do established invertebrate models for aging, and thus rotifers may be used to investigate novel genetic mechanisms relevant to human lifespan and healthspan. The research on caloric restriction; dietary, pharmaceutical, and genetic interventions; and transcriptomics of aging using rotifers provide insights into the metabolic regulators of lifespan and health and suggest future directions for aging research. Capitalizing on the unique biology of Brachionus rotifers, referencing the vast existing literature about the influence of diet and drugs on rotifer lifespan and health, continuing the development of genetic tools for rotifers, and growing the rotifer research community will lead to new discoveries a better understanding of the biology of aging.

Sphingolipids, a major class of lipids in cell membranes, play diverse roles in biology. They are synthesized by a highly conserved biosynthetic pathway that leads to the production of ceramides, the major precursors of most complex sphingolipids. Almost all known stress stimuli including inflammatory agonists, chemotherapeutics, and saturated fatty acids induce the synthesis of ceramide and its metabolites. A panoply of recent studies has implicated ceramides in the development of the metabolic comorbidities of obesity such as diabetes and cardiovascular diseases. In particular, inhibition of ceramide biosynthesis in rodents ameliorates insulin resistance, diabetes, cardiomyopathy, atherosclerosis, and steatohepatitis. These data implicate ceramides as major contributors to the development of metabolic diseases. This review summarizes recent findings on this emerging class of bioactive lipids with an emphasis on studies using in vivo models to understand their role in metabolic disease.

Probiotics and prebiotics have been the subject of extensive investigations into their role in human health including their effects on risk of age-related chronic diseases. There is good evidence that probiotics and, to a lesser extent prebiotics, can influence immune function in older subjects and counteract immunosenescence and increased inflammation. Probiotics have also been shown to increase the effectiveness of influenza vaccination in the elderly and reduce risk and/or duration of upper respiratory tract infections. Prebiotics and probiotics have been shown to have benefits for common gastrointestinal disorders that are common in older people, especially constipation, and there is some evidence that symptoms of metabolic syndrome can be alleviated by certain probiotics.

This review aims to highlight some aspects regarding anthocyanins bioavailability. Although there is a considerable variability in the values for the biokinetic parameters, anthocyanins appear to be rapidly absorbed and eliminated, reaching low maximal concentrations in plasma and urine. Nevertheless, some works have reported a high content of intact anthocyanins in plasma, possibly resulting from gastric absorption. So far, no anthocyanin metabolites have been detected in the stomach and the possible mechanism of anthocyanin gastric absorption is still unknown. Some progress in this field is expected to be obtained through studies involving a new human cell culture model of the gastric surface suitable for bioavailability screening of nutraceuticals like anthocyanins and anthocyanin-derived pigments. The positive health effects associated with anthocyanin consumption could derive from the contribution afforded by the stomach to intact anthocyanin absorption. Nonetheless, these latter may be further metabolized to other bioactive forms.

A current lack of consensus exists regarding the effect of protein supplementation during resistance exercise on the phenotypic adaptation in aging adults. Thus, we critically assessed the collection of meta-analytic evidence to provide clarity regarding the differences between meta-analyses examining the combined effectiveness of chronic exposure to PRO/AA supplementation and resistance exercise to enhance the adaptive response. Thirteen meta-analyses, with relatively similar titles, presented different results on the topic. This divergence is mainly due to an inconsistent study selection process resulting in distinct study populations and varied types of protein-focused nutritional interventions and not RCT study quality. The methods applied to extract and estimate effects from RCTs with incorrectly formatted data for meta-analyses likely provide an additional reason for divergent results. PRO/AA supplements (when combined with resistance exercise training) produced a positive, albeit minor effect on the promotion of whole-body lean mass growth, yet a minimal and inconsistent effect on muscle mass, muscle strength, or functional capacity. The lack of an effect was skewed in studies with a higher proportion of obese and overweight participants and somewhat less noticeable in those containing sarcopenic and frail older adults, who would have the greatest need for an intervention to enhance muscle mass. Researchers are encouraged to provide the change scores mean and standard deviations for all their outcomes by group or even making the data sets available to improve future meta-analyses and advance the field.

The human gut microbiota alters with the aging process. In the first 2-3 years of life, the gut microbiota varies extensively in composition and metabolic functions. After this period, the gut microbiota demonstrates adult-like more stable and diverse microbial species. However, at old age, deterioration of physiological functions of the human body enforces the decrement in count of beneficial species (e.g. Bifidobacteria) in the gut microbiota, which promotes various gut-related diseases (e.g. inflammatory bowel disease). Use of plant-based diets and probiotics/prebiotics may elevate the abundance of beneficial species and prevent gut-related diseases. Still, the connections between diet, microbes, and host are only partially known. To this end, genome-scale metabolic modeling can help to explore these connections as well as to expand the understanding of the metabolic capability of each species in the gut microbiota. This systems biology approach can also predict metabolic variations in the gut microbiota during ageing, and hereby help to design more effective probiotics/prebiotics.

Literature reviews suggest flavonoids, a sub-class of polyphenols, are beneficial for cognition. This is the first review examining the effect of consumption of all polyphenol groups on cognitive function. Inclusion criteria were polyphenol vs. control interventions and epidemiological studies with an objective measure of cognitive function. Participants were healthy or mildly cognitively impaired adults. Studies were excluded if clinical assessment or diagnosis of Alzheimer's disease, dementia, or cognitive impairment was the sole measure of cognitive function, or if the polyphenol was present with potentially confounding compounds such as caffeine (e.g. tea studies) or Ginkgo Biloba. 28 studies were identified; 4 berry juice studies, 4 cocoa studies, 13 isoflavone supplement studies, 3 other supplement studies, and 4 epidemiological surveys. Overall, 16 studies reported cognitive benefits following polyphenol consumption. Evidence suggests that consuming additional polyphenols in the diet can lead to cognitive benefits, however, the observed effects were small. Declarative memory and particularly spatial memory appear most sensitive to polyphenol consumption and effects may differ depending on polyphenol source. Polyphenol berry fruit juice consumption was most beneficial for immediate verbal memory, whereas isoflavone based interventions were associated with significant improvements for delayed spatial memory and executive function. Comparison between studies was hampered by methodological inconsistencies. Hence, there was no clear evidence for an association between cognitive outcomes and polyphenol dose response, duration of intervention, or population studied. In conclusion, however, the findings do imply that polyphenol consumption has potential to benefit cognition both acutely and chronically.

Chronic diseases, such as cardiovascular disease, cancers, chronic respiratory diseases, diabetes mellitus, and neurodegenerative disorders represent major global health problems to society, and their incidence and prevalence continue to increase. Chronic diseases share common risk factors, including socio-economic factors and co-morbidities and, importantly, their risk increases with age. The silent transition from health to disease with a late onset of symptoms can delay treatment and interventions. Healthcare-systems must thus evolve proactive rather than purely reactive approaches to care once symptoms appear. Many self-tracking technologies (based on wireless biosensors) are readily available to the general public that monitor and record personal bio-related data. These biosensors may be wearable, implanted in the body or installed on a device. The aim of this review is to discuss the current market and proven utility of wrist-worn devices, in improving and maintaining a healthy lifestyle. Optimizing the technological opportunities for monitoring good health has the potential to empower people and help many enjoy a high quality of life.

Insulin resistance (IR) could play a role in neurodegenerative diseases (ND). The high-fructose (HF) diet is an IR model in rats. The vitamin A-deprived (VAD) rat is known to develop large similarities with ND within only 14 weeks post-weaning. Since VAD symptoms are partly reversible and independent of any IR mechanism, this ND model was used to investigate (i) a potential additional effects of IR in a ND context, and (ii) a possible preventive strategy when resveratrol (RSV) is added to the diet. Male Wistar rats were fed from weaning to 15–19 weeks: control, HF (60%), VAD and a combination HF+VAD; some control, VAD and VAD + HF rats were force-fed with trans-RSV (54 μg/100 g weight). In addition to assessing blood parameters (IR or inflammation), nuclear magnetic resonance (NMR) allowed both: (i) a longitudinal follow-up of brain anatomical (MRI) and early micro-structural changes (diffusion tensor imaging) and (ii) a metabolomic study of brain and liver (¹H HRMAS spectroscopy) at key points in the diets. An early decrease (<6 weeks) in fractional anisotropy in hippocampus was evidenced in VAD and preceded other impairments. HF diet induced biological IR from week 9 but brain metabolomic changes were already detected from week 5. In contrast, no brain morphologic change was observed. VAD + HF diet impaired rat health, enhanced the retinolemia VAD-induced decrease and increased ventricular volume vs both HF and VAD. Presence of RSV decreased IR, maintained retinol and attenuated the ventricular volume increase, probably via AMPKinase activation. Interestingly, these results allowed us to determine a sequence in brain impairments; first, micro structural changes, followed by metabolic disturbances and later on morphological modifications.

BACKGROUND: Skeletal muscle atrophy during aging, a process known as sarcopenia, is associated with muscle weakness, frailty, and the loss of independence in older adults. The mechanisms contributing to sarcopenia are not totally understood, but muscle fiber loss due to apoptosis, reduced stimulation of anabolic pathways, activation of catabolic pathways, denervation, and altered metabolism have been observed in muscle from old rodents and humans.

OBJECTIVE: Recently, histone deacetylases (HDACs) have been implicated in muscle atrophy and dysfunction due to denervation, muscular dystrophy, and disuse, and HDACs play key roles in regulating metabolism in skeletal muscle. In this review, we will discuss the role of HDACs in muscle atrophy and the potential of HDAC inhibitors for the treatment of sarcopenia.

CONCLUSIONS: Several HDAC isoforms are potential targets for intervention in sarcopenia. Inhibition of HDAC1 prevents muscle atrophy due to nutrient deprivation. HDAC3 regulates metabolism in skeletal muscle and may inhibit oxidative metabolism during aging. HDAC4 and HDAC5 have been implicated in muscle atrophy due to denervation, a process implicated in sarcopenia. HDAC inhibitors are already in use in the clinic, and there is promise in targeting HDACs for the treatment of sarcopenia.

The concept of frailty refers to heterogeneity in the risk of adverse outcomes for people of the same age. It is traditionally thought of as the inability of the body to maintain homeostasis. It can help explain differences between chronological and biological age and can quantify healthspan in experimental studies. Although clinical studies have developed tools to quantify frailty over the past two decades, preclinical models of frailty have only recently been introduced. This review describes the notion of frailty and outlines two commonly used clinical approaches to quantify frailty: the frailty phenotype and the frailty index. Translation of these methodologies for use in animals is introduced and studies that use these models to evaluate interventions designed to attenuate or exacerbate frailty are discussed. These include studies involving manipulation of diet, implementation of exercise regimens and tests of pharmaceutical agents to exacerbate or attenuate frailty. Together, this body of work suggests that preclinical frailty assessment tools are a valuable new resource to quantify the impact of interventions on overall health. Future studies could deploy these models to evaluate new frailty therapies, test combinations of interventions and assess interventions to enhance the ability to resist stressors in the setting of ageing.