Research finds biomarkers in older adults with late-life depression (Senescent cells)

Major depression in older adults is very common, disabling, and increases the risk of many diseases of aging, including Alzheimer's disease and other dementias, cardiovascular issues and even mortality.

Many older adults with depression do not experience full resolution of their depressive symptoms with antidepressant treatment. Improving or achieving full resolution of depression in older adults is a major clinical challenge, and approximately 50% of patients experience persistent depressive symptoms after antidepressant treatment. The persistence of depressive symptoms becomes a source of depleted psychological well-being, increased disability, accelerated cognitive decline, and premature aging in older adults.

Therefore, identifying the mechanisms and factors associated with treatment outcomes in this population is key for improving therapeutics and identifying those individuals for whom antidepressant treatment would be more effective.

Dr. Breno Diniz addressed these in a study. They used a composite biomarker index associated with cellular and molecular senescence [the senescence-associated secretory phenotype, SASP] to test the hypothesis that biological changes that occur with aging are one of the mechanisms of poor treatment outcomes in older adults with depression. They found that higher SASP index scores were significantly associated with a lower likelihood of full resolution of the depressive symptoms after antidepressant treatment.

These findings are important because they highlight the importance of age-related biological abnormalities, reflected in the SASP index, as a potential mechanism related to treatment resistance to antidepressants in older adults. This investigation opens up new possibilities to investigate alternative interventions, for example, by testing whether senolytic drugs can improve rates of treatment remission in older adults with depression. Also, the measurement of the SASP index biomarkers can help to identify those individuals in which treatment would be futile at the treatment outset.

These findings inform a path forward for interventions targeting senescence to improve depressive symptoms in older adults.

It would appear senescent cells help create conditions for depression. These are cells that remain in our bodies, but do not get recycled, as they did when we were younger. It is largely responsible for the effects of aging we notice.

There are now proven ways to address this, to a large extent. Senolytics are drugs and supplements that cause apoptosis of cells, which is the natural elimination of dysfunctional cells our bodies used to always use. Cell parts get recycled. Doing this in older people has been found to be helpful.

Other options revive the cells. GlyNAC does this by removing cellular inflammation. In studies, it allowed 80 year olds to have a walking gait that was faster than that of 30 year olds, for instance, along with many other health factors nearing that of 30 year olds. Also, a supplement called Urolithin A forces mitophagy, which is the apoptosis of just the defective mitochondria in our cells, followed by new mitochondria to replace those just eliminated. Mitochondria our the energy powerhouses in our cells. Imagine taking both together! (My wife and I are currently trying this.)

These have all been previously posted, here on Free Republic, if interested. The GlyNAC daily amount Nestle Celltrient suggests (it bought the patent) is 1,200 mg of glycine and 1,200 mg of NAC a day, but the study with the 80 year olds used over five times that amount. You can make GlyNAC cheaply from those two amino acids bought from a store. For the Urolithin A, which is also available from Nestle, 500 or 1,000 mg a day is what has been used in human trials.

Prior senolytic threads described apigenin, fisetin, and quercetin as possible senolytic options.

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