News — The molecular mechanisms underlying the natural aging of cells remain inadequately comprehended. Analyzing situations in individuals where genetic factors expedite the aging process offers chances to gain insights into the regulatory mechanisms governing aging and develop tactics to decelerate the aging progression.
Adults with Down Syndrome (DS) exhibit premature indications of age-related ailments: diminished tissue regenerative ability, alopecia, parched skin, delayed wound healing, persistent gum disease, osteoporosis, and senescence of brain and immune cells. DS is a genetic disorder, non-heritable in nature, caused by the presence of an additional copy of chromosome 21 (trisomy 21) at birth. It affects approximately 7 million individuals globally (approximately 60,000 in the UK).
DS stands as the most prevalent genetic origin of intellectual disability and early-onset Alzheimer's disease. The augmented susceptibility to early Alzheimer's disease can be directly attributed to the presence of an additional copy of the amyloid precursor protein gene (APP), which is encoded on chromosome 21. However, the genetic underpinnings for the other associated conditions are not readily explicable.
In a recent study published in the Lancet Discovery journal eBioMedicine, a team led by Professor Dean Nižetić and Dr. Aoife Murray from Queen Mary University, in collaboration with institutions from Croatia, Singapore, France, Italy, and four other universities in London, has revealed that an excessively active gene on chromosome 21 triggers premature aging of cells in individuals with DS.
According to the study, individuals with DS have been found to exhibit a biological age that is, on average, 19.1 years older than their chronological age-matched counterparts without DS. Remarkably, the research indicates that this accelerated aging process is not attributed to co-existing health conditions associated with DS and begins early in childhood. The primary cause of the premature aging component in DS has been identified as an excessive expression of the DYRK1A gene, which encodes a kinase enzyme that accelerates chemical reactions in the body. This overdose of the gene disrupts the mechanisms responsible for repairing DNA damage, leading to an increased occurrence of DNA breaks and cell nuclei fragility.
Dean Nižetić, Professor of Cell and Molecular Biology at Queen Mary, said:
The study findings have revealed that the excessive expression of the DYRK1A gene due to trisomy is a significant factor in the premature biological aging observed in DS. However, further research is required to elucidate the extent of its impact on brain development and function. Additionally, exploring methods to effectively inhibit the excessive expression of this gene and restore it to normal physiological levels could present promising avenues for early interventions in DS. It is important to emphasize that extensive research is still necessary before such interventions can be developed and implemented.
Carol Boys, Chief Executive of the Down’s Syndrome Association, commented:
For a considerable duration, it has been recognized that individuals with Down Syndrome undergo an accelerated aging process that seems to progress more rapidly compared to the general population.
The publication of this landmark research study, conducted by esteemed researchers collaborating on an international level, marks a significant milestone. Notably, the study brings forth the possibility of potential treatments that could intervene in the accelerated cellular aging process. This particular aspect of the research holds immense importance and is bound to generate substantial interest among individuals with Down Syndrome and their families, as it offers hope for future advancements and improved quality of life.
Furthermore, the research has demonstrated that diminishing the activity of the gene, either through genetic or chemical means, holds promise in correcting the cellular aging abnormalities. This discovery unveils potential opportunities for early therapeutic interventions in individuals with DS, with the aim of mitigating the adverse effects of premature biological aging on their overall development and well-being. Moreover, these findings contribute to a deeper understanding of the intrinsic mechanisms of aging and highlight genes that could be targeted to delay the natural aging process and reduce the susceptibility to age-related diseases commonly observed in the general population.
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