Salk researchers show how two experimental Alzheimer’s drugs protect the brains of mice from other aspects of aging
In mouse models of Alzheimer’s disease, the investigational drug candidates known as CMS121 and J147 improve memory and slow the degeneration of brain cells. Now, Salk researchers have shown how these compounds can also slow aging in healthy older mice, blocking the damage to brain cells that normally occurs during aging and restoring the levels of specific molecules to those seen in younger brains.
The research, published last month in the journal eLife, suggests that the drug candidates may be useful for treating a broader array of conditions and points out a new pathway that links normal aging to Alzheimer’s disease.
“This study further validated these two compounds not only as Alzheimer’s drug candidates but also as potentially more widely useful for their anti-aging effects,” says Pamela Maher, a senior staff scientist at Salk and a co-corresponding author of the new paper.
Old age is the biggest risk factor for Alzheimer’s disease—above the age of 65, a person’s risk of developing the disease doubles about every five years. However, at a molecular level, scientists aren’t sure what occurs in the brain with aging that contributes to Alzheimer’s.
“The contribution of old age-associated detrimental processes to the disease has been largely neglected in Alzheimer’s disease drug discovery,” says Antonio Currais, a Salk staff scientist and first author of the new paper.
Maher and David Schubert, the head of Salk’s Cellular Neurobiology Lab, previously developed CMS121 and J147, variants of plant compounds with medicinal properties. Both compounds tested positive for their ability to keep neurons alive when exposed to cellular forms of stress related to aging and Alzheimer’s disease. Since then, the researchers have used the drug candidates to treat Alzheimer’s in animal models of the disease. But experiments revealing exactly how the compounds work suggested that they were targeting molecular pathways also known to be important in longevity and aging.
In the new research, Maher, Currais and their colleagues turned to a strain of mice that ages unusually fast. A subset of these mice was given CMS121 or J147 beginning at nine months old—the equivalent of late middle age in humans. After four months, the team tested the memory and behavior of the animals and analyzed genetic and molecular markers in their brains.
Not only did the animals given either of the drug candidates perform better on memory tests than mice that hadn’t received any treatment, but their brains showed differences at the cellular and molecular levels. In particular, expression of genes associated with the cell’s energy-generating structures called mitochondria was preserved by CMS121 and J147 with aging.
“The bottom line was that these two compounds prevent molecular changes that are associated with aging,” says Maher.
More detailed experiments showed that both drugs affected mitochondria by increasing levels of the chemical acetyl-coenzyme A (acetyl-coA). In isolated brain cells, when the researchers blocked an enzyme that normally breaks down acetyl-CoA, or when they added extra amounts of an acetyl-coA precursor, they saw the same beneficial effect on mitochondria and energy generation. The brain cells became protected against the normal molecular changes associated with aging.
“There was already some data from human studies that the function of mitochondria is negatively impacted in aging and that it’s worse in the context of Alzheimer’s,” says Maher. “This helps solidify that link.”
Maher and Currais are planning future experiments to test the effects of CMS121 and J147 on how other organs age. They also hope to use the new results to inform the development of new Alzheimer’s drugs; targeting other molecules in the acetyl-coA pathway may help treat the disease, they hypothesize.
“We are now using a variety of animal models to investigate how this neuroprotective pathway regulates specific molecular aspects of mitochondrial biology, and their effects on aging and Alzheimer’s,” says Currais.
Go deeper with Bing News on:
- Seven easy anti-ageing tips ‘ripped 60-year-old’ swears by – from barefoot forest walks to breathing trick
WELLNESS gurus are an interesting bunch, but few, if any, are quite as eye-catching as Troy Casey. A charismatic chap currently residing in Arizona, Casey is, for lack of a better word, ...
- Skincare fans snap up Boots £25 beauty box that contains 'powerful' £35 anti-ageing serum
Skincare Edit is worth over £116, saving shoppers more than £90 on top-name brands like La Roche-Posay and No7 ...
- Skincare brand launch 'miracle' cleanser to 'slow down signs of ageing' and remove makeup
Taking your makeup off at the end of a long day is a lovely feeling - but not so much when you find yourself spending ages scrubbing away for your complexion to be left feeling dry, irritated and not ...
- How ageing Britain put retirement at risk
They are more likely to be disabled and less likely to get on the housing ladder.On top of all of this, they will have to shoulder the massive cost of funding the state pension for the generations ...
- Bad Boys star, 58, looks like she’s ageing backwards after a career comeback 29 years after co-starring with Will Smith
BAD Boys star Tèa Leoni is stepping back into the world of acting nearly three decades after starring alongside Will Smith. The actress, who played Julie Mott in the hit 1995 action comedy, is ...
Go deeper with Google Headlines on:
[google_news title=”” keyword=”ageing” num_posts=”5″ blurb_length=”0″ show_thumb=”left”]
Go deeper with Bing News on:
- Gwen Stefani’s ‘Aging Clothes’ and ‘Transformed Face’ Are to ‘Please’ Blake Shelton, Fashion Psychologist Claims
Gwen Stefani's fashion transformation might be to 'please' Blake Shelton, a fashion psychologist says. Here's why.
- Researchers say education might slow pace of aging
"Upward educational mobility was significantly associated with a slower pace of aging and lower risk of death," the School of Public Health's team said in a press release Friday. To reach their ...
- Women in their 50s and 60s love this anti-aging tool that's nearly 25% off: 'So easy to use and fast results'
A trusted resource in any esthetician’s beauty arsenal, a high-frequency treatment is typically offered as part of a luxurious spa facial. The NuDerma kit brings similar benefits to your home but for ...
- GMFS Area Agency on Aging!
Charlotte Foust with the Area Agency on Aging joined Howie this morning to talk all about their upcoming town hall meeting to discuss the Missouri Master Plan On Aging! Next Friday, March 8th, from ...
- Educational Achievement Slows Aging
Researchers discovered a link between educational attainment and biological aging, using data from the Framingham Heart Study.
Go deeper with Google Headlines on:
[google_news title=”” keyword=”aging” num_posts=”5″ blurb_length=”0″ show_thumb=”left”]