A blood test that measures the impact of aging on cells could help to guide care among older adults with depression. It could be used to identify those at higher risk of dementia and potentially other health issues that are common in those with late-life depression.
The test, known as the SASP index – which stands for “senescence-associated secretory phenotype” – was developed by CAMH Clinician Scientist Dr. Breno Diniz and his team. The index measures 22 proteins that appear after cells change as people age, and also among those with depression.
In a new study funded by the U.S. National Institute of Mental Health, Dr. Diniz, a geriatric psychiatrist, will validate the use of the SASP index in clinical care. Dr. Diniz, who is originally from Brazil, joined CAMH in 2016, coming from the University of Texas Health Science Center.
How will this help patients?
If you’re elderly, a diagnosis of depression can be challenging enough. But late-life depression also increases the risk of developing other health problems including Alzheimer’s disease and other forms of dementia, as well as diabetes, high blood pressure, heart attacks and frailty.
On a hopeful note, dementia prevention is an active and promising area of research. In addition, not everyone with late-life depression has a higher chance of developing these conditions.
This is where the SASP index could play an important role. “We want to identify people with depression who are at increased risk of Alzheimer’s disease,” explains Dr. Diniz. “These individuals could be targeted for interventions to prevent dementia.”
The SASP index helps identify those at risk. People with late-life depression have a higher SASP index score than older adults without depression. Those with higher scores also do worse on memory and other cognitive tests. “There could be structural brain changes,” he says.
The current study will take a comprehensive approach in examining the link between the SASP index and the cognitive symptoms of late-life depression, such as memory loss, and track changes in these patients over time. The study will also include MRI brain imaging and molecular and cellular profiling.
“We hope to find new targets to treat depression in older adults and to prevent dementia and other negative consequences,” he says. Potential treatments include a class of drugs called senolytics, which are already used in treatment for other illnesses, such as metformin for diabetes treatment. Nutraceuticals, food-derived products developed for treatment, are another possibility.
From cell biology to clinical test
At the root of this area of research is the fundamental question, “What are the biological processes that lead to aging?” says Dr. Diniz.
When we’re younger, our cells make copies of themselves for growth, or to repair damage. With aging or with certain medical conditions, cells deteriorate and replication stops. These cells are known as senescent cells. Senescence is a natural process that occurs in everyone, and over time, senescent cells accumulate in the body.
These senescent cells can be identified by proteins and other biomarkers, which Dr. Diniz used along with statistical modelling to develop the SASP index. The index reflects the level of molecular senescence. Senescence has also been seen in younger people with depression, and is associated with poorer health, tobacco use, medical problems and cardiovascular disease.
“The SASP index can be a very good marker of senescence in general,” says Dr. Diniz. The index may have applications for other brain-based and aging-related illnesses, as senescence is an active area of medical research.
