Aging and dementia has common links, including the mitochondrial α-F1 -ATP synthase (ATP5A), which can be a target for the Alzheimer's disease drug candidate J147. The mTOR signaling pathway is involved with this; abstract:
Aging is a major driving force underlying dementia, such as that caused by Alzheimer's disease (AD). While the idea of targeting aging as a therapeutic strategy is not new, it remains unclear how closely aging and age-associated diseases are coupled at the molecular level. Here, we discover a novel molecular link between aging and dementia through the identification of the molecular target for the AD drug candidate J147. J147 was developed using a series of phenotypic screening assays mimicking disease toxicities associated with the aging brain. We have previously demonstrated the therapeutic efficacy of J147 in several mouse models of AD. Here, we identify the mitochondrial α-F1 -ATP synthase (ATP5A) as a target for J147. By targeting ATP synthase, J147 causes an increase in intracellular calcium leading to sustained calcium/calmodulin-dependent protein kinase kinase β (CAMKK2)-dependent activation of the AMPK/mTOR pathway, a canonical longevity mechanism. Accordingly, modulation of mitochondrial processes by J147 prevents age-associated drift of the hippocampal transcriptome and plasma metabolome in mice and extends lifespan in drosophila. Our results link aging and age-associated dementia through ATP synthase, a molecular drug target that can potentially be exploited for the suppression of both. These findings demonstrate that novel screens for new AD drug candidates identify compounds that act on established aging pathways, suggesting an unexpectedly close molecular relationship between the two.
Are you afraid of dementia? How about developing dementia in your 40s? You might be able to protect yourself ... by learning about the food for the brain.
By “food for the brain” I do not mean reading books and learning. True, challenging your brain is important based upon the “use it, or lose it” rule. However, in this post I am referring to the actual food you consume every day.
Do you eat lots of sugar? Have you been putting on pounds? Are you frequently tired? Are you moody most of the time? If you are not worried about your waistline and appearance, are you worried about succumbing to a dreadful illness due to your body weight?
Are you on the verge of being diagnosed with diabetes type 2? Or do you already have it? Do you have metabolic syndrome? Do you think that these conditions are not a problem because they could be controlled by medications?
I assure you that one body “malfunction” now would lead to another malfunction down the road, in your older years. If you escape cardiovascular diseases and cancer (both linked to overweight/obesity, metabolic syndrome, and insulin resistance), you may not be lucky to escape dementia associated with many different types of neurodegenerative diseases.
Both insulin resistance and diabetes are linked to several neurodegenerative diseases, including Alzheimer’s. Here is a source for more information.
In some neurodegenerative diseases, glucose is not properly used in the brain, and this situation is reminiscent of diabetes and insulin resistance. In fact, Alzheimer’s disease is sometimes called “type 3 diabetes”. And here is the bombshell: not only we may witness our children develop cancer before us, but we may also have to take care of our children when they develop dementia in their 40s:
"At a time in history when type 2 diabetes is diagnosed in progressively younger adults, the [new] findings have important implications for age of Alzheimer’s disease — with symptoms that will be increasingly reported by adults in their 50s and even possibly even in their 40s.”
Actionable
Stop eating sugar, stop drinking anything with sugar or sweeteners. Learn to read nutrition labels and recognize all 50+ names of sugar. Get the excess weight down.
And yes, mental exercise helps too:
You know what they say, use it or lose it. For a healthy brain functions, do these as described here:
· Challenge yourself
· Be socially active
· Follow a healthy diet
· Be physically active
· Reduce stress
· Protect your head
· Make healthy lifestyle choices
· Do your brain a favour - volunteer!
