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:
- Dorset LEP seeks funding bids for innovation in healthy ageing and net zero
A CALL has gone out for innovations in the areas of healthy ageing or net zero infrastructure which would merit investment of up to £10million.
- Coastal Court prepared suitably for ageing occupants
Designing a home for a couple that aim for this to be their last, Bower Architecture has created Coastal Court, a dwelling that encourages privacy and a connection to nature that doesn’t require ...
- Central Goldfields Shire Council adopts Ageing Strategy
Council has adopted its Positive Ageing Strategy at last week's council meeting. During June, council underwent community feedback and engaged with 650 residents during the drafting phase. The draft ...
- Global Anti-Ageing Drugs Market Forecasting Revenue of Market and Estimating Revenue Show big Move in 2021
The Anti Ageing Drugs market report for the Anti Ageing Drugs market is an assemblage of first hand data along with the quantitative and qualitative valuation and analysis for the forecast period 2021 ...
- 'Maybe it's All in Blood': Could Bats Hold the Key to Healthy Ageing?
Bats not only live longer than other animals of their size, they also stay healthy longer and can harbour pathogens like Ebola or coronaviruses without getting sick.
Go deeper with Google Headlines on:
Go deeper with Bing News on:
- Census figures reflect aging of rural Utah
While most of the world was on pandemic lockdown last year, Lisa Jeppson and her husband put more than 2,000 miles on their side-by-side ATV ...
- Department of Aging seeks community partners to host falls-prevention walks
The agency is seeking community partners to help raise awareness by hosting local walking groups and events to contribute to a statewide total of ...
- This 'Magical' Anti-Aging Serum Leaves Supple, Smooth Skin in Its Wake
The brand's custom superberry blend of maqui (a very antioxidant-rich fruit), acai, prickly pear, and goji berry—alongside jojoba oil, rosehip oil, moringa oil, and squalane—prevent free radicals from ...
- Russia's Aging T-80 Tank Is Getting a Firepower Boost
Despite the large numbers produced, and the efforts to keep the ubiquitous T-80 upgraded, it was only first deployed in combat during the First Chechen War in 1994. To say it didn't go well is a bit ...
- Aging-US: Spatiotemporal dynamics of γH2AX after acute irradiation
The Aging-US results suggest that early life irradiation-induced PDDF at later stages of animal life may be related to the brain aging and shortened life expectancy of irradiated animals.