New study reveals ways to help protect bones as we age

Latest articles

Cellino bags $80 million to autonomise stem cell therapy manufacturing

Leaps by Bayer leads $80m Series A to enable Cellino to significantly expand patient access to stem cell-based therapies. Cellino Biotech, Inc, an autonomous stem cell...

“World’s first” cultural-matching app for care sector launches

Care receivers can be paired with carer based on religious understanding and culture thanks to AI tech developed during pandemic. A graduate has created what...

Biotech LyGenesis expands its liver regeneration tech

A new peer-reviewed paper demonstrates the success of using fat-associated lymphoid clusters as expandable niches for ectopic liver regeneration. LyGenesis, a clinical-stage biotech developing cell...

NURO embarks on funding round for neurotech communication system

World’s first multimodal neurotech operating system from NURO allows you to communicate using just your brain. DISCLOSURE: Longevity.Technology (a brand of First Longevity Limited) has...

Most read

New supplement slows aging and promotes weight loss

Sugar-proof your way to a longer life. Reducing AGEs to slow aging and increase weight loss – how one supplement is fighting the war...

An antiaging supplement that also reduces appetite?

One for the AGEs: Juvify signs IP licensing deal with Buck Institute for GLYLO antiaging supplement that aims to reduce glycation. A researcher at the...

Resveratrol – the small molecule with big antiaging ideas

When it comes to antiaging molecules, we can learn a thing or two from plants. As so often in natural world, plants have a few...

Editor's picks

Cellino bags $80 million to autonomise stem cell therapy manufacturing

Leaps by Bayer leads $80m Series A to enable Cellino to significantly expand patient access to stem cell-based therapies. Cellino Biotech, Inc, an autonomous stem cell...

“World’s first” cultural-matching app for care sector launches

Care receivers can be paired with carer based on religious understanding and culture thanks to AI tech developed during pandemic. A graduate has created what...

Biotech LyGenesis expands its liver regeneration tech

A new peer-reviewed paper demonstrates the success of using fat-associated lymphoid clusters as expandable niches for ectopic liver regeneration. LyGenesis, a clinical-stage biotech developing cell...

Click the globe for translations.

Tackling aging sometimes needs a left-field approach – especially when it comes to protecting our bones.

Aging affects us right down to our bones; bone mass or density is lost with age, and this especially affects women post-menopause. Bones lose calcium and other minerals and hip and knee joints suffer the degenerative loss of cartilage. Add to this calcification of joints due to mineral deposits, brittle bones that break more easily and a gradual breaking down of joints that can lead to inflammation, pain and deformity and it’s clear why research in this area is of longevity interest.

Longevity.Technology: The damaging process of aging can weaken our bones, exacerbating conditions such as osteoarthritis, sarcopenia and frailty. Our skeleton isn’t just under threat from the passage of time; drugs like prednisone, a common corticosteroid that is used to treat many different conditions such as hormonal disorders, arthritis, lupus, ulcerative colitis, Crohn’s, asthma, kidney disorders and multiple sclerosis can also weaken our bones. Now scientists are working to prevent bone weakening caused by both aging and drugs have discovered evidence that the best target may not be the logical one.

Dr Meghan McGee-Lawrence, biomedical engineer in the Department of Cellular Biology and Anatomy at the Medical College of Georgia, and her team have found that in aging bone, the mineralocorticoid receptor, which is better known for its role in blood pressure regulation, is a key factor in bone health. Drugs that block the receptor, like the hypertension medications spironolactone and eplerenone, may help protect bone cells, reveals the study, published in the Journal of Bone and Mineral Research.

Drugs like prednisone are glucocorticoids are better known for their roles in reducing inflammation and suppressing the immune response, which is why they work so well for problems like irritable bowel syndrome and arthritis. However, like aging, they can also disrupt the healthy, ongoing bone cycle of destruction and creation.

The body has natural glucocorticoid levels and these increase with age; when we are young, bone has more glucocorticoid receptors than mineralocorticoid receptors and glucocorticoids have a neat trick of being able to coax stem cells to make bone-forming osteoblasts, but this is a double-edged sword as this causes those osteoblasts to store more fat. Too much fat in the bone, just like anywhere on our body, is not a good thing and typically correlates with bone loss, says McGee-Lawrence.

The upshot is that reducing the impact of glucocorticoid receptors seemed to be, to the MCG scientists, a logical way to protect bone. The research team had previously been surprised to discover that a depletion of functioning glucocorticoid receptors did not guard against bone loss in younger mice when fed calorie-restricted diets. Rather, an increase in fat accumulation in the bone marrow and a worsening of osteoporosis was observed.

In this study, the team looked at the impact of endogenous glucocorticoids in an aging model; again, they discovered that when the glucocorticoid receptor was blocked, older mice also experienced more fat accumulation in the bone marrow and worsening bone disease. The mice also had a smaller muscle mass, were less active and had higher blood pressure.

When the researchers used drugs to inhibit the mineralocorticoid receptor, many of the problems were reversed [2].

“The only way we have found to get rid of that lipid storage by osteoblasts was to inhibit the mineralocorticoid receptor with drugs,” says McGee-Lawrence, explaining that due to the receptors’ clear role in blood pressure there are already drugs that do that. “I think what it means is if we want to understand what these stress hormones, these endogenous glucocorticoids, are doing we cannot just think about signalling through one receptor,” she added [1].

When it comes to older bones, McGee-Lawrence feels that mineralocorticoid receptors might present a better target as they are thought to have equal affinity for mineralocorticoids and glucocorticoids, and it may be the case that it is the signalling paths that are different in young and older individuals. “We thought that knocking out the glucocorticoid receptor would make things better, but it made them worse,” she explains. “We think the mineralocorticoid receptor may explain a lot of what is going wrong in aging bone [1].”

The team already have some evidence that bone’s expression of mineralocorticoid receptors goes up as you age, and by a degree that has potential significance; the results for whether glucocorticoid receptors go down with age are mixed, and the next step is to explore what happens with both receptor levels as well as discovering more about the role of mineralocorticoid receptors in bone, particularly aging bone.

“We want to know what would cause bone cells to change which receptors they are expressing and how they are responding to these,” she says. “But there are a lot of things that happen with aging. We know inflammation changes with aging, so there are a lot of different cues that could cause these things to change [1].”

The whole body impact they saw from their manipulation of receptors, like a higher blood pressure from deleting the glucocorticoid receptor, also is evidence of bone’s importance as an endocrine organ, she says.

“By changing glucocorticoid signalling in the bone, not only are we seeing changes in the bone, but we are seeing changes in the fat, muscle, adrenal glands, in physical activity,” McGee-Lawrence says [1]. This means something from the bone is communicating with all these other body systems, an emerging area of research in this field.

In fact, the increased fat presence in the bone marrow found in osteoporosis has resulted in it also being considered a metabolic disease of the bone; this is similar to the way obesity, particularly excess weight around the middle, is considered a metabolic disease. Increased fat in the bone marrow is associated with disuse, such as after a spinal cord injury, or because of a high-fat diet, taking glucocorticoids, like steroids, and aging.

While fat is a ready energy source for bone cells, too much can hinder bone cell formation. The scientists don’t yet know whether the cells are no longer using fat well or if they are pulling more in, or both; they do know fat accumulating in the bone cells coincides with less bone being made, McGee-Lawrence reiterates.

“We are trying to figure out exactly why these things are going wrong so that we can pick the right avenue to pursue for a treatment strategy,” she says [1].

Evidence shows that synthetic glucocorticoids, taken via pill or injection, can impact bone, and this can create an unhealthy imbalance between the amount of bone made and the amount broken down, but it may be that both our natural endogenous glucocorticoids and synthetic glucocorticoids work through these alternative receptors to damage the bone. Trying to prevent this damage could mean a different target as well as varying goalposts, as the pathways might change with age.

[1] https://jagwire.augusta.edu/new-target-may-help-protect-bones-as-we-age/
[2] https://asbmr.onlinelibrary.wiley.com/journal/15234681

Photograph: Michael Holahan, Augusta University
Eleanor Garth
Deputy Editor Now a science and medicine journalist, Eleanor worked as a consultant for university spin-out companies and provided research support at Imperial College London and various London hospitals in a former life.

Most popular

New supplement slows aging and promotes weight loss

Sugar-proof your way to a longer life. Reducing AGEs to slow aging and increase weight loss – how one supplement is fighting the war...

An antiaging supplement that also reduces appetite?

One for the AGEs: Juvify signs IP licensing deal with Buck Institute for GLYLO antiaging supplement that aims to reduce glycation. A researcher at the...

Resveratrol – the small molecule with big antiaging ideas

When it comes to antiaging molecules, we can learn a thing or two from plants. As so often in natural world, plants have a few...

Sugar-proof your health with the GLYLO weight loss and antiaging supplement

Move your New Year's resolution up a gear with GLYLO, a double-action supplement that can increase weight loss while also slowing aging. Choosing an effective...

Related articles

Cellino bags $80 million to autonomise stem cell therapy manufacturing

Leaps by Bayer leads $80m Series A to enable Cellino to significantly expand patient access to stem cell-based therapies. Cellino Biotech, Inc, an autonomous stem cell...

Biotech LyGenesis expands its liver regeneration tech

A new peer-reviewed paper demonstrates the success of using fat-associated lymphoid clusters as expandable niches for ectopic liver regeneration. LyGenesis, a clinical-stage biotech developing cell...

Exercise protects brain against Alzheimer’s by safeguarding synapses

UCSF researchers find enhanced nerve transmission is seen in older adults who remain active. When elderly people stay active, their brains have more of a...

Mental illness drug discovery company Neurai Life Sciences launches

AI will drive discovery of innovative small molecules and next generation therapies to treat mental health disorders. Wuhan, a bioceutical company focused on alternative plant-based...

StarkAge secures 2 million euros for senescence targeting therapy

Funding from Bpifrance's Deeptech program will drive development of company’s immunotherapy approach targeting cellular senescence in age-related disease. French biotech startup StarkAge Therapeutics today announced...

    Subscribe to our newsletter