New findings show that much of the mineral from which bone is made consists of ‘goo’ trapped between tiny crystals, allowing movement between them. It is this flexibility that stops bones from shattering.
Latest research shows that the chemical citrate – a by-product of natural cell metabolism – is mixed with water to create a viscous fluid that is trapped between the nano-scale crystals that form our bones.
This fluid allows enough movement, or ‘slip’, between these crystals so that bones are flexible, and don’t shatter under pressure. It is the inbuilt shock absorber in bone that, until now, was unknown.
If citrate leaks out, the crystals – made of calcium phosphate – fuse together into bigger and bigger clumps that become inflexible, increasingly brittle and more likely to shatter. This could be the root cause of osteoporosis.
The team from Cambridge’s Department of Chemistry used a combination of NMR spectroscopy, X-ray diffraction, imaging and high-level molecular modelling to reveal the citrate layers in bone.
They say that this is the start of what needs to be an entire shift in focus for studying the cause of brittle bone diseases like osteoporosis, and bone pathologies in general. The study is published today in the journal Proceedings of the National Academy of Sciences.
“Bone mineral was thought to be closely related to this substance called hydroxyapatite. But what we’ve shown is that a large part of bone mineral – possibly as much as half of it in fact – is made up of this goo, where citrate is binding like a gel between mineral crystals,” said Dr Melinda Duer, who led the study.
“This nano-scopic layering of citrate fluid and mineral crystals in bone means that the crystals stay in flat, plate-like shapes that have the facility to slide with respect to each other. Without citrate, all crystals in bone mineral would collapse together, become one big crystal and shatter.
“It’s this layered structure that’s been missing from our knowledge, and we can now see that without it you’re stuffed.”
Duer compares it to two panes of glass with water in the middle, which stick together but are able to slide: “it’s the same thing in these flat bone crystals. But you’ve got to have something that keeps the water there, stops it from drying out and stops the plates from either flying apart or sticking fast together. We now know that thing is citrate.”
Citrate is a ‘spidery’ molecule with four arms, all of which can bond easily to calcium – which bone is packed with, explains Duer. This means that citrate can hold the mineral crystals together at the same time as preventing them from fusing, while trapping the water that allows for the slippery movement which provides bone flexibility. “Without citrate, water would just flow straight through these gaps,” she said.
The body actually delivers bone calcium wrapped in citrate, to prevent it fusing with phosphate and forming large solid – and brittle – mineral crystals in the wrong places. Bone tissue has a protein mesh with holes where the calcium is deposited. In healthy tissue, the holes are very small, so that when the calcium is deposited, the citrate that comes with it can’t escape and is trapped between crystals – creating the flexible layers of fluid and bone plates.
As people age or suffer repeated bone trauma, the protein mesh isn’t repaired so well by the cells that try to replace damaged tissue, but often end up chewing away tissue faster than it can be re-deposited. This causes progressively larger holes in the protein mesh, citrate fluid escapes and crystals fuse together.
What happens then is pure chemistry, says Duer, with little biological control.
The body instigates a form of biological control through the tiny holes in the protein mesh that trap the citrate fluid, along with other molecules that normally control the deposit of mineral. These small spaces force the molecules to be involved with the forming mineral, controlling the process. But if you haven’t got the confined space the chemical reactions spiral out of control.
“In the bigger holes in damaged tissue, pure chemistry takes over. Pretty much the moment calcium and phosphate touch, they form a solid. You end up with these expanding clumps of brittle crystal, with water and citrate relegated to the outside of them,” she said.
“In terms of chemistry, that solid clump of mineral is the most stable structure. Biomechanically, however, it’s hopeless – as soon as you stand on it, it shatters. If we want to cure osteoporosis, we need to figure out how to stop the bigger holes forming in the protein matrix.”
The study is the first in a series of findings, with other studies from the team’s work on bone chemistry expected to come out later in the year.
15 October 2013 BioMed Central Limited
How this DNA Age Calculator came about may be a little techie for most, but the impacts from this new tool offers new understandings about how cells age and it may even predict disease far earlier than before. Maybe once we understand how we breakdown, our elusive, cellular fountain of youth may finally become more accessible. If we can have 3D printers, why not? I’m just saying.
Using thousands of tissue samples from open access datasets, a scientist has created a calculator which predicts the age of tissue using chemical changes to DNA. Research published in the open access journal Genome Biology explains how the calculator works.
Professor Steve Horvath, of UCLA, used data from 7844 samples in 82 publicly available datasets to create a calculator which predicts the age of healthy tissue using information about changes in DNA methylation.
Traditionally, changes to telomeres, the bits of genetic code at the end of chromosomes, are used to tell the age of tissues. Horvath showed that DNA methylation is a much more accurate measure.
DNA methylation is a chemical change that is made to DNA throughout life – previous studies have shown that as we get older, certain changes to the methylation of DNA accumulate.
This article demonstrates that, in almost all healthy tissues and cell types, the accumulation happens at a predictable rate and explains how he used the DNA methylation data and the actual age of tissues in 39 datasets to work out that rate and create a calculator.
Some tissue types were shown to buck this trend, however. Breast tissue appeared older while heart tissue appeared younger than expected. Analysis of an additional 5826 cancer tissue samples showed that certain types of brain, breast and colorectal cancers had an accelerated rate of DNA aging, giving hints about how cancer affects tissue and suggesting new methods to diagnose certain cancer types.
Professor Horvath said: “These results are a testimony to the collaborative spirit of the epigenetics community and the benefits of open access to data sets. This study would not have been possible without freely accessible data repositories such as Gene Expression Omnibus, ArrayExpress, and The Cancer Genome Atlas (TCGA).”
Professor Horvath developed a multi-tissue predictor of age that allows one to estimate the DNA methylation age of most tissues and cell types. The predictor, which is freely available, was developed using 8,000 samples from 82 Illumina DNA methylation array datasets, encompassing 51 healthy tissues and cell types.
He found that DNA methylation age has the following properties:
- first, it is close to zero for embryonic and induced pluripotent stem cells;
- second, it correlates with cell passage number;
- third, it gives rise to a highly heritable measure of age acceleration; and,
- fourth, it is applicable to chimpanzee tissues.
Analysis of 6,000 cancer samples from 32 datasets showed that all of the considered 20 cancer types exhibit significant age acceleration, with an average of 36 years.
Low age-acceleration of cancer tissue is associated with a high number of somatic mutations and TP53 mutations, while mutations in steroid receptors greatly accelerate DNA methylation age in breast cancer. Finally, he characterizes the 353CpG sites that together form an aging clock in terms of chromatin states and tissue variance.
A study carried out on ninety-year-olds reveals the benefits of
strength training as physical exercise
27 September 2013 Elhuyar Fundazioa
After doing specific training for 12 weeks, people over the age of 90 improved their strength, power and muscle mass. This was reflected in an increase in their walking speed, a greater capacity to get out of their chairs, an improvement in their balance, a significant reduction in the incidence of falls and a significant improvement in muscle power and mass in the lower limbs.
These are some of the outcomes of the study recently published in the journal Age of the American Ageing Association and which was led by Mikel Izquierdo-Redín, Professor of Physiotherapy at the NUP/UPNA-Public University of Navarre.
24 people between 91 and 96 participated in the research, eleven of them in the experimental group and 13 in the control group. Two days a week over a 12-week period they did multicomponent training: a programme of various exercises designed specifically for them and which combined strength training and balance improving exercises. As Mikel Izquierdo explained, “the training raised their functional capacity, lowered the risk of falls, and improved muscle power. In addition to the significant increases in the physical capacity of frail elderly people, the study has shown that power training can be perfectly applied to the elderly with frailty.”
With ageing, the functional capacity of the neuromuscular, cardiovascular and respiratory system progressively starts to diminish, and this leads to an increased risk of frailty. Physical inactivity is one of the fundamental factors that contributes to the loss of muscular mass and functional capacity, a key aspect in frailty.
“From a practical point of view,” says Prof Izquierdo, “the results of the study point to the importance of implementing exercise programmes in patients of this type, exercises to develop muscle power, balance and walking.” In his view, “it would be beneficial to apply exercises of this type among vulnerable elderly people to prevent the impact of ageing, improve their wellbeing and help them to adapt to the society in which they live.”
The piece of research which has been echoed by the American Ageing Association is entitled: “Multicomponent exercices including muscle power training enhance muscle mass, power output and functional outcomes in instituzionalized frail nonagenarians”.
01 July 2013 British Psychological Society (BPS)
Society should have a more favorable attitude towards sexual activity in older people because of the many benefits it brings.
That is the message of a paper being presented Friday, 5 July 2013, by Dr David Weeks, a consultant clinical psychologist and former Head of Old Age Psychology at the Royal Edinburgh Hospital. Dr Weeks will be addressing the Annual Conference of the British Psychological Society’s Faculty of the Psychology of Older People in Colchester.
In his paper, Dr Weeks will make clear the relevance of exploratory research on people with eccentric behaviours and personality, and of research on people who look and feel significantly younger than their chronological age, to the health, longevity and especially the sex lives of the general population.
Drawing on his 38 years of clinical practice and research, he will argue that the key ingredients for looking younger are staying active and maintaining a good sex life.
Dr Weeks says: “When people contemplate ageing their thinking is riven with negative stereotypes and ageist myths – those who are most prejudiced against older people know them least. And misconceptions of this kind generate irrational prohibitive feelings, making sexual experiences less enjoyable for both partners within a relationship.
“Yet the quality of sexual expression maintained in older adults is a predictor of good general health and well-being. In a Welsh heart disease study from 1997, the mortality risk was 50 per cent lower in the group of men with high orgasmic frequency (twice a week or more) than in the group with low frequency.
“Sexual satisfaction is a major contributor to quality of life, ranking at least as high as spiritual or religious commitment and other morale factors, so more positive attitudes towards mature sex should be vigorously promoted.
“Sexuality is not the prerogative of younger people and nor should it be.”