MIT researchers discover ‘anti-aging molecule’ that can heal DNA lesions associated with Alzheimer’s disease
MIT researchers discover ‘anti-aging molecule’ that can heal DNA lesions associated with Alzheimer’s disease and cognitive decline from aging
- Researchers identified the enzyme HDAC1 as helpful in curing DNA damage
- As people age, lesions form on parts of their DNA that decrease cognitive function
- HDAC1 stimulates the production of another enzyme that can heal these lesions
A new joint study by MIT and Harvard has identified an enzyme that can help reverse the effects of DNA damage from aging and Alzheimer’s disease.
The researchers, led by MIT’s Li-Huei Tsai and Harvard’s Stephen Haggarty, identified an enzyme called HDAC1 that can help repair 8-oxoguanine lesions on DNA strands, which have been linked to age-related cognitive decline and Alzheimer’s disease.
Subjects with fewer of these lesions showed significantly improved cognitive performance, memory ability and basic spatial awareness.
Researchers identified an enzyme that can heal DNA lesions associated with cognitive decline and Alzheimer’s disease. Scans of mice with an abundance of HDAC1 (top row) had fewer lesions, shown as dark green spots, than mice without HDAC1 (bottom row)
“It looks like HDAC1 is really an anti-aging molecule,” Tsai said MIT News.
‘I think this is a very broadly applicable basic biological finding, because almost all human neurodegenerative diseases only occur during aging. I would like to speculate that activating HDAC1 is beneficial in many circumstances. ‘
Tsai and Haggerty tested their theory on mice by genetically engineering some to not produce HDAC1 and comparing them as they aged with a control group with normal levels of HDAC1.
Although there were no significant differences initially, the mice without the ability to produce HDAC1 developed DNA lesions faster than before the control and showed a decrease in memory tests and spatial navigation.
HDAC1 regulates the production of a separate enzyme, OGG1, which can repair these DNA lesions, but as HDAC1 production decreases with age, the brain’s ability to heal itself also decreases.
The researchers hope that a safe chemical treatment can be found to stimulate HDAC1 production in humans to cure the accumulation of DNA lesions that build up with age.
In previous research, Tsai and her team determined that HDAC1 production could be stimulated with the drug exifone, which was commonly prescribed as a treatment for dementia in the 1980s.
The drug was discontinued in humans after it was shown to cause liver damage, but in tests in mice, Tsai showed that it stimulated HDAC1 production and improved cognitive and memory performance in mice.
Tsai also found that the mice had a significant reduction in lesions after receiving exiphon.
“This study really positions HDAC1 as a potential new drug target for age-related phenotypes, as well as neurodegeneration-associated pathology and phenotypes,” Tsai said.
While the team doesn’t advocate prescribing exifone to humans, the findings make them hopeful that a similar but safer drug can be found to boost HDAC1 production as a treatment for cognitive decline and Alzheimer’s disease.
WHAT IS ALZHEIMER?
Alzheimer’s disease is a progressive, degenerative brain disease in which nerve cells die due to the accumulation of abnormal proteins.
This disrupts the channels that contain messages and causes the brain to shrink.
More than 5 million people suffer from the disease in the US, where it is the 6th leading cause of death, and more than 1 million Britons have it.
WHAT IS HAPPENING?
When brain cells die, the functions they provide are lost.
That includes memory, orientation, and the ability to think and reason.
The progress of the disease is slow and gradual.
Patients live an average of five to seven years after diagnosis, but some can live ten to 15 years.
- Loss of short-term memory
- Behavioral changes
- Mood swings
- Difficulty handling or calling money
- Severe amnesia, forgetting close relatives, familiar objects or places
- Becoming anxious and frustrated at the inability to understand the world, leading to aggressive behavior
- Ultimately lose the ability to walk
- Can have problems with eating
- The majority ultimately require care 24 hours a day
Source: Alzheimer’s Association