MIT researchers discover ‘anti-aging molecule’ that can heal DNA lesions linked with Alzheimer’s disease and cognitive declines from aging

  • Researchers identified the enzyme HDAC1 as helpful in healing DNA damage
  • As people age, lesions form on parts of their DNA that lowers cognitive function
  • HDAC1 stimulates production of another enzyme that can heal these lesions

A new joint study from MIT and Harvard has identified an enzyme that could help reverse the effects of DNA damage associated with 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.

Test subjects with fewer of these lesions exhibit significantly improved cognitive performance, memory ability and basic spatial awareness.

Researchers identified an enzyme that can heal DNA lesions linked to cognitive decline and Alzheimer’s. Scans from mice with an abundance of HDAC1 (top row) had fewer lesions, shown as dark green spots, than mice with no HDAC1 (bottom row)

‘It seems that HDAC1 is really an anti-aging molecule,’ Tsai told MIT News.

‘I think this is a very broadly applicable basic biology finding, because nearly all of the human neurodegenerative diseases only happen during aging. I would speculate that activating HDAC1 is beneficial in many conditions.’

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.

While there were no significant differences initially, over time the mice without the ability to produce HDAC1 developed DNA lesions at a faster rate than for the control and they showed declines 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, so does the brain’s ability to heal itself.   

The researchers are hopeful that a safe chemical treatment can be found to help stimulate the production for HDAC1 in humans to heal the accumulation of DNA lesions that build up with age

In earlier research, Tsai and her team established that HDAC1 production could be stimulated with the drug exifone, which had been commonly prescribed in the 1980s as a treatment for dementia.

The drug had been discontinued on humans after it was shown to cause liver damage, but in tests on mice, Tsai showed it stimulated the production of HDAC1 and improved the cognitive ability and memory performance in mice.

Tsai also found that the mice had a significant reduction in lesions after being given exifone.

‘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 isn’t advocating for exifone to be prescribed to humans, the findings make them hopeful a similar but safer drug could be found to stimulate HDAC1 production as a treatment for cognitive decline and Alzheimer’s.

WHAT IS ALZHEIMER’S?

Alzheimer’s disease is a progressive, degenerative disease of the brain, in which build-up of abnormal proteins causes nerve cells to die.

This disrupts the transmitters that carry 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 HAPPENS?

As 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. 

On average, patients live five to seven years after diagnosis, but some may live for ten to 15 years.

EARLY SYMPTOMS:

  • Loss of short-term memory
  • Disorientation
  • Behavioral changes
  • Mood swings
  • Difficulties dealing with money or making a phone call 

LATER SYMPTOMS:

  • Severe memory loss, forgetting close family members, familiar objects or places
  • Becoming anxious and frustrated over inability to make sense of the world, leading to aggressive behavior 
  • Eventually lose ability to walk
  • May have problems eating 
  • The majority will eventually need 24-hour care   

 Source: Alzheimer’s Association

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