Ageing brings many challenges, including cognitive decline and mobility issues. These problems can increase the risk of Alzheimer’s disease and loss of independence. Scientists believe that one major contributor to these issues is the accumulation of senescent cells. These ageing cells stop dividing but continue to release harmful inflammatory molecules. Over time, they damage surrounding tissues, leading to chronic inflammation and degeneration.
Senolytics, a class of drugs that selectively remove these cells, have gained attention as a potential way to slow ageing-related diseases. Preclinical studies suggest that eliminating senescent cells can improve physical and cognitive function in animal models. However, the effectiveness and safety of these drugs in humans remain uncertain.
A new study led by researchers from Harvard Medical School explored whether two senolytic compounds, Dasatinib and Quercetin (DQ), could help older adults with early signs of cognitive decline and mobility issues.
The Study: Testing Senolytics in Older Adults
The research team conducted a 12-week trial involving 12 participants, all aged 65 or older, who had mild cognitive impairment and slow walking speed. These two factors are often early indicators of Alzheimer’s disease. The participants took 100 mg of Dasatinib and 1250 mg of Quercetin for two consecutive days every two weeks.
The researchers measured several key indicators:
- Cognitive function using the Montreal Cognitive Assessment (MoCA) and the Trail Making Test.
- Mobility through gait speed and dual-task walking tests.
- Inflammatory markers in blood samples, particularly tumor necrosis factor-alpha (TNF-α), a protein linked to brain inflammation and cognitive decline.
Cognitive and Mobility Improvements
The results suggested potential benefits, especially for participants who had the lowest cognitive scores at the start of the study.
Cognitive function: Overall, MoCA scores increased by one point, which was not statistically significant. However, in participants with the lowest initial scores, the average improvement was two points, a change considered clinically meaningful. The Trail Making Test also showed signs of improvement, with participants completing tasks faster after the intervention.
Mobility: Participants demonstrated modest improvements in walking speed and stride length, particularly while performing cognitive tasks. This suggests that senolytics might help maintain coordination and multitasking ability, both of which decline with age.
Reducing Inflammation for Brain Health
One of the most interesting findings was the reduction in TNF-α levels after treatment. TNF-α is a major inflammatory marker associated with cognitive decline. Researchers found that as TNF-α levels dropped, MoCA scores increased, suggesting a possible link between reduced inflammation and improved brain function.
Although these results are promising, the researchers cautioned that this was a small pilot study without a placebo group. More extensive trials are needed to confirm the effects of senolytics on cognition and mobility.
Safety and Side Effects
A key objective of the study was to determine the safety of intermittent senolytic treatment. The results were reassuring.
No serious adverse events were linked to the drugs.
Minor side effects such as fatigue, mild gastrointestinal discomfort, and slight reductions in white blood cell counts were observed but were not severe.
High compliance rates: Participants took nearly all their prescribed doses, suggesting that the treatment was well tolerated.
These findings support the feasibility of using senolytics in older adults, but researchers emphasized the need for caution. The long-term effects of these drugs remain unknown, and future studies should include larger, more diverse groups to ensure safety across different populations.
The Future of Senolytics in Ageing Research
Senolytic research is still in its early stages, but this study adds to the growing body of evidence suggesting that targeting senescent cells could be a promising strategy for maintaining brain health. If larger studies confirm these findings, senolytics may eventually become a new tool in preventing or delaying Alzheimer’s disease.
Future research should focus on:
- Expanding the sample size to include more participants with diverse backgrounds.
- Using a placebo-controlled design to ensure that observed improvements are due to senolytics and not other factors.
- Studying long-term effects to determine whether intermittent senolytic treatment provides sustained cognitive and mobility benefits.
Alzheimer’s disease remains one of the biggest challenges in ageing research. While senolytics are not a cure, they represent a new and promising approach that may help slow cognitive decline and improve quality of life for older adults.
The study is published in the journal EBioMedicine. It was led by Courtney L. Millar from Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife.
