How old are you? Before you respond, there might be more than one answer. We have all noticed that there are always some individuals who seem to age slowly, have plenty of energy and vitality and don’t suffer from too many diseases. There is a reason for this.
The first answer to this question is of course your astronomical age, the number of times the Earth has rotated on its axis or around Sol. If this metric was relevant then we might all age in precisely the same manner. There is another metric that likely offers a more realistic measure of biological age and offers some indication about your likely longevity. Fitness Age!
This test is hosted by and managed by the university and has no advertising or “payment options”.
There are a number of reasons why this test is significant. The lower your Fitness Age relative to your astronomical age, the lower your mortality risk and that has to be a good thing. Secondly you can use the “Back” key to alter the inputs and see what changes to your lifestyle mean to your effective mortality risk.
A very interesting study in Cell Metabolism demonstrates that energy-controlled high-fat low carbohydrate diets are not detrimental to health, but rather a ketogenic diet (with a very high proportion of fat) extends lifespan and slows age-related decline in physiological function in mice.
Calorie restriction (CR) has long been shown to increase longevity in animal models. However longitudinal studies in humans are not possible. The exact mechanism for contributing to increased longevity in CR animal models remains unresolved however it has long been recognised that CR induces a shift from carbohydrate to fat metabolism. Low carbohydrate diets (LCD) have been shown to induce a shift from carbohydrate towards fatty acid oxidation metabolism.
In this paper the authors have studied the most extreme LCD, the ketogenic diet in an animal model. They studied mice by strictly regulating their diet and generated three cohorts: LCD group fed 70% of their kcal as fat, a KD group fed 89% of their kcal as fat and a control group fed 65% of their kcal as carbohydrate.
The results of the study have confirm earlier studies which showed that a KD promoted an anti-inflammatory metabolic state with elevated blood ketone levels comparable to CR. This study however goes well beyond previous studies following the population from birth to post-mortem. The primary objective of this study was the evaluate the influence of LCD and KD on longevity and health-markers in mice.
The results of this study include:
The results clearly demonstrate that lifespan is increased in mice consuming a KD when a feeding strategy is followed that mitigates weight gain in adult mice. It is often assumed that a high-fat diet will shorten life expectancy however, this study indicate that a calorie-controlled LCD started in middle-aged mice does not have a negative impact on aging. Further evidence does not support the idea that level of protein is primarily responsible for the increased longevity;
This study shows that a KD slows cognitive decline and preserves motor function in aging mice. KD maximizes and preserves forelimb grip strength with age. Respiratory quotient was decreased by an LCD or a KD compared to a control diet.
KD mice showed glucose intolerance however insulin sensitivity after a 4 hr fast was enhanced by a KD if compared to the LCD, indicating that insulin signalling is functioning normally in mice fed a KD
Ketones would appear to positively impact muscle homeostasis and may play an important role as neuro-protective signalling molecules
The level of acetylated p53, a key tumour suppressor protein, was 10-fold higher in liver after 1 month on a KD and as a likely consequence, incidence of tumours at time of death, particularly histiocytic sarcoma, was decreased with a KD
A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice
Megan N. Roberts, Marita A. Wallace, Alexey A. Tomilov, Zeyu Zhou, George R. Marcotte, Dianna Tran, Gabriella Perez, Elena Gutierrez-Casado, Shinichiro Koike, Trina A. Knotts, Denise M. Imai,
Stephen M. Griffey, Kyoungmi Kim, Kevork Hagopian, Fawaz G. Haj,
Keith Baar, Gino A. Cortopassi, Jon J. Ramsey, Jose Alberto Lopez-Dominguez
Calorie restriction, without malnutrition, has been shown to increase lifespan and is associated with a shift away from glycolysis toward beta-oxidation. The objective of this study was to mimic this metabolic shift using low-carbohydrate diets and to determine the influence of these diets on longevity and healthspan in mice. C57BL/6 mice were assigned to a ketogenic, low-carbohydrate, or control diet at 12 months of age and were either allowed to live their natural lifespan or tested for physiological function after 1 or 14 months of dietary intervention. The ketogenic diet (KD) significantly increased median lifespan and survival compared to controls. In aged mice, only those consuming a KD displayed preservation of physiological function. The KD increased protein acetylation levels and regulated mTORC1 signaling in a tissue-dependent manner. This study demonstrates that a KD extends longevity and healthspan in mice.
Obesity has become a real worldwide epidemic with an estimated 700 million people being so classified. A new report in the latest issue of New England Journal of Medicine highlights the issues and the conclusion are truly alarming. This collaborative (~200 researchers) research (funded by the Gates foundation) evaluated the trends in the prevalence of the overweight and obesity as well as the patterns of deaths and disability-adjusted life-years related to high BMI, according to age and sex, in 195 countries. This analysis supersedes all previous results from the Global Burden of Disease study with respect to high BMI by comprehensively reanalyzing all data from 1990 through 2015 using consistent methods and definitions.
Here are their key findings
In 2015, an estimated 604 million adults and 108 million children worldwide were obese. That represents about 12% of all adults and 5% of all children.
The prevalence of obesity doubled in 73 countries between 1980 and 2015 and continuously increased in most of the other countries.
China and India had the highest number of obese children. China and the U.S. had the highest number of obese adults.
Excess body weight accounted for about 4 million deaths — or 7.1% of all deaths — in 2015.
Almost 70 percent of deaths related to a high BMI were due to cardiovascular disease.
The study finds evidence that having a high BMI causes leukemia and several types of cancer, including cancers of the esophagus, liver, breast, uterus, ovary, kidney and thyroid.
In rich and poor countries, obesity rates increased, indicating “the problem is not simply a function of income or wealth. Changes in the food environment and food systems are probably major drivers. Increased availability, accessibility, and affordability of energy-dense foods, along with intense marketing of such foods, could explain excess energy intake and weight gain among different populations. The reduced opportunities for physical activity that have followed urbanization and other changes in the built environment have also been considered as potential drivers; however, these changes generally preceded the global increase in obesity and are less likely to be major contributors.”
The level of obesity across the western world is nothing short of alarming and will place enormous strain on an already burdened health case system. Not surprisingly the USA is the fattest nation on the planet with a staggering 38% of the population over 15 YO being classified as obese and the percentage of obese women is even higher. The USA also holds the record for age-standardised childhood obesity, at 12.7%. Australia, Canada, Mexico, UK and several European nations are not far behind.
Age Standardized Prevalence of Obesity Worldwide in 2015
More alarmingly there has been a rapid increase in obesity levels across the world, driven by an abundance of high-energy food and effective marketing.
Relative Percent Change in Obesity Prevalence between 1980 and 2015 for Males >20
Relative Percent Change in Obesity Prevalence between 1980 and 2015 for Feales >20
It just seems that when large portions of the human population have ready access to food they simply cannot stop themselves from eating. A portion of the issue is likely genetics. Humans in cold climates that more efficiently converted calories into fat-stores were better able to survive the winter and better able to care for their offspring and had a higher chance of passing on their genes.
This advantage however fails the host when there is an inexhaustible supply of high calorific value food and exhaustible supply of will power or intelligence.
Health Effects of Obesity
There are consequences for obesity as well all know and these consequences are very expensive for the public health systems and devastating for the individuals concerned.
Epidemiological evidence supporting causality between high BMI and disease
Education has simply failed. In the west for too long, at schools and across the media excessive consumption and obesity have been major public health issues. The shopkeepers have done a fantastic job in generating products and spaces which are appealing to consumers. They have rarely acted in the public interest for example, adding salt and excessive sugar to breakfast cereals because it results in consumer addiction.
It is time for somewhat more dramatic measures. Western government could instigate 20% sugar and fat taxes on fast foods (in addition to existing consumer taxes) and reduce consumer taxes to zero on healthy alternatives for example unprocessed fruit and vegetables. If this fails in addition to education then health care billing related to BMI could be a more draconian measure. It is time to tax fat and reduce obesity.
Although the rising pandemic of obesity has received major attention in many countries, the effects of this attention on trends and the disease burden of obesity remain uncertain.
We analyzed data from 68.5 million persons to assess the trends in the prevalence of overweight and obesity among children and adults between 1980 and 2015. Using the Global Burden of Disease study data and methods, we also quantified the burden of disease related to high body-mass index (BMI), according to age, sex, cause, and BMI in 195 countries between 1990 and 2015.
In 2015, a total of 107.7 million children and 603.7 million adults were obese. Since 1980, the prevalence of obesity has doubled in more than 70 countries and has continuously increased in most other countries. Although the prevalence of obesity among children has been lower than that among adults, the rate of increase in childhood obesity in many countries has been greater than the rate of increase in adult obesity. High BMI accounted for 4.0 million deaths globally, nearly 40% of which occurred in persons who were not obese. More than two thirds of deaths related to high BMI were due to cardiovascular disease. The disease burden related to high BMI has increased since 1990; however, the rate of this increase has been attenuated owing to decreases in underlying rates of death from cardiovascular disease.
The rapid increase in the prevalence and disease burden of elevated BMI highlights the need for continued focus on surveillance of BMI and identification, implementation, and evaluation of evidence-based interventions to address this problem. (Funded by the Bill and Melinda Gates Foundation.)
While the left and the media fret about Climate Change here is the real and present threat. Far more than 100,000 people will DIE from antibiotic resistant bacteria in 2017. In 2016 in the USA 2 million people contracted an antibiotic resistant infection and 23, 000 died.
We are spending billions on climate change research and mitigation programs and near to nothing on this critical threat. The number of people who will die from climate change in 2017 – Zero! While antibiotic additives have been banned in some jurisdictions of recent times the use of antibiotics in agriculture is endemic. Pigs only metabolise 10% of ingested antibiotics and the rest finds its way into the environment, in to stream and rivers and fish ponds. This has been an obvious problem for 30 years yet there seems to be no call to action and our remarkably uneducated politicians seem incapable of understanding the imminent danger posed to their voters.
Carbapenem-resistant Enterobacteriaceae (CRE) present an urgent threat to public health. While carbapenem antimicrobials are restricted in food-producing animals, other lactams, such as ceftiofur, are used in #livestock. This use may provide selection pressure favoring the amplification of carbapenem resistance but this relationship has not been established. Previously unreported from US livestock, plasmid-mediated CREs have been reported from livestock in Europe and Asia.
Environmental and fecal samples were collected from a 1,500 sow, US farrow-to-finish operation during 4 visits over a 5 month period, 2015. Samples were screened using selective media for the presence of CRE, with resulting carbapenemase-producing isolates further characterized.
Of 30 environmental samples collected from a nursery room on our initial visit, 2 (7%) samples yielded 3 isolates: 2 ST 218 Escherichia coli and 1 Proteus mirabilis, carrying the metallo-lactamase gene blaIMP-27 on IncQ1 plasmids. We recovered 15 IMP-27-bearing isolates of multiple Enterobacteriaceae species from 11 of 24 (46%) environmental samples from 2 farrowing rooms collected on our third visit. These isolates each also carried blaIMP-27 on IncQ1 plasmids. No CRE isolates were recovered from fecal swabs or samples in this study.
As is common in US swine production, piglets on this farm receive ceftiofur at birth, with males receiving a second dose at castration (day 6). This selection pressure may favor the dissemination of blaIMP-27-bearing Enterobacteriaceae in this farrowing barn. The absence of this selection pressure in the nursery and finisher barns likely resulted in the loss of the ecological niche needed for maintenance of this carbapenem resistance gene.
Shenshen Lai and colleagues from the University of British Columbia report results from a study of protein kinases in eukaryotes (A eukaryote is any organism whose cells contain a nucleus and other organelles enclosed within membranes.
Protein kinases play a pivotal role in communicating intracellular signals in eukaryotes. The family of eukaryotic protein kinases (ePKs) comprises of at least 568 human members, which accounts for more than 2% of protein coding genes of the entire human genome. These kinases are highly conserved both their primary amino acid sequences in the 3D structures of their catalytic domains. Because of the central regulatory roles the high conservation of the ePKs, the ancestry of these enzymes has become an important question in the study of the evolution eukaryotic organisms.
The ePKs and ChPK are responsible for amongst other things the construction of the cell membrane (which allow the development of organelles including the nucleus to develop) and communication between organelles within the cell. They are likely responsible for the evolution and success of organisms larger than prokaryotic organisms like for example bacteria which lack a nucleus and membrane bounded organelles. Without the early horizontal transfer and preservation of GlnRS life as we know it would likely not exist. GlnRS is found in all complex organisms including plants and animals.
Eukaryotic life is believed to have evolved between 1.7 to 2.7 billion years ago and no living representatives of the earliest eukaryotes survive today. Consequently, the actual origin of protein kinases is difficult to establish with a high degree of confidence.
They conclude that ePKs and ChPKs in eukaryotes evolved from an ancient common mRNA source (possibly at the commencement of life on earth – or at least very early). While these proteins are highly degenerate this team has identified two class-I aminoacyl-tRNA synthetases with high similarities to consensus amino acid sequences of human protein-serine/threonine kinases suggesting that horizontal transfer early in evolution gave rise to many contemporary genes.
This research provides solid argument for the continuity of life on early for much of the last 3 billion years and our genetic relationship to the earliest lifeforms on this planet.
Original Research: Shenshen Lai et al. Evolutionary Ancestry of Eukaryotic Protein Kinases and Choline Kinases, Journal of Biological Chemistry (2016). DOI: 10.1074/jbc.M115.691428
This study looked at the relationship between a high-fat diet and the how this impacted stem and progenitor cell function. They found that a HFD in the mammalian intestine modulated a strong peroxisome proliferator-activated receptor delta (PPAR-delta) response in stem cells. PPAR-delta not only alters the function of intestinal stem cells but importantly non-intestinal progenitor cells nearby allowing the development and growth of intestinal tumors.
Mice on the HFD saw a 30-50% weight gain with a much higher incidence of intestinal tumors than control mice on a normal diet. The researchers saw a significant increase in the number of stem cell in mice on a HFD and importantly the stem cells appeared to grow in a manner which suggested that they were not receiving input immediately adjacent cells – the normal route to cell growth. Non-stem, progenitor cells in the intestinal walls also started to act like stem cells and exhibited significantly longer lives.
There has been clear epidemiological evidence for a strong link between obesity and colorectal cancer and this study provides a clear and concise mechanism for tumor initiation and propagation. If you are on a HFD its time to change.
High-fat diet enhances stemness and tumorigenicity of intestinal progenitors
Little is known about how pro-obesity diets regulate tissue stem and progenitor cell function. Here we show that high-fat diet (HFD)-induced obesity augments the numbers and function of Lgr5+ intestinal stem cells of the mammalian intestine. Mechanistically, a HFD induces a robust peroxisome proliferator-activated receptor delta (PPAR-delta) signature in intestinal stem cells and progenitor cells (non-intestinal stem cells), and pharmacological activation of PPAR-delta recapitulates the effects of a HFD on these cells. Like a HFD, ex vivo treatment of intestinal organoid cultures with fatty acid constituents of the HFD enhances the self-renewal potential of these organoid bodies in a PPAR-delta-dependent manner. Notably, HFD- and agonist-activated PPAR-delta signalling endow organoid-initiating capacity to progenitors, and enforced PPAR-delta signalling permits these progenitors to form in vivo tumours after loss of the tumour suppressor Apc. These findings highlight how diet-modulated PPAR-delta activation alters not only the function of intestinal stem and progenitor cells, but also their capacity to initiate tumours.