It is an innovative approach in assessing personal risk for age-related diseases proposed by Dorothee Dormann and Edward Lemke, who are researchers at Johannes Gutenberg University Mainz and adjunct directors at the Institute of Molecular Biology. Their idea described in the perspective article—a “protein aggregation clock”—in Nature Cell Biology tells how protein clumps in cells can be measured to determine the aging process of a person and their health condition.
Gradual changes in DNA and proteins contaminate the body over time, ultimately affecting physiological function and paving the way for diseases associated with aging, from cardiovascular and cancer diseases to neurodegenerative disorders such as Alzheimer’s disease. Protein aggregation is a major phenomenon associated with the process of aging, in which misfolded proteins clump together to form aggregates usually known as amyloids.
It overlaps particularly well with the intrinsically disordered proteins, a subset of proteins without a rigid structure and thus highly dynamic. According to Dormann and Lemke, these IDPs—each making up about 30% of cellular proteins—are prone to misfolding and aggregation, particularly within the groups of long-lived cells like neurons or muscle cells. Such aggregates build up and are associated with the progress of many age-related diseases, most of which concern the nervous system.
In their article, Dormann and Lemke put this forward to suggest monitoring IDP aggregation as a biomarker or “clock” of biological aging, which should allow prediction of susceptibility to age-related disease in an individual. On a theoretical note, such a protein-aggregation clock would revolutionize early disease detection and facilitate preemptive intervention prior to the manifestation of symptoms when developed into a precision diagnostic tool. It might also be very good, for example, in assessing the efficacies of experimental treatments aiming to reduce protein aggregation and in this way delay or totally prevent age-related disease.
While this may yield a very promising protein aggregation clock, Dormann and Lemke are aware of where they start from in current knowledge and stress that much further research is required before mechanisms of IDP aggregation are clear. This will underline how improvements in knowledge about the dynamics of IDPs go hand in hand with technological progress relating to reading this potentially new biological clock for its usage.
Herewith, one realizes that the protein aggregation clock is a radical departure from the traditional model of biological clocks that are based mostly on nucleic acids like DNA. Since proteins take part in every cellular process and are abundantly available, they provide a complementary approach to the existing assays of aging and health. Dormann and Lemke propose incorporating this protein-centered view within the general context of research aimed at understanding healthy aging and the development of intervention strategies against diseases with an age component.
The work is an integral part of the newly launched Center for Healthy Ageing, which was set up in 2021 at Mainz as a research networking platform, bringing together basic and clinical research expertise in ageing and age-related diseases. Results from this research are foreseen not only fundamentally to improve knowledge related to ageing processes but also enable the development of targeted therapies that wish to promote healthy ageing and reduce the burden of age-associated diseases.
On this front, Dormann and Lemke’s proposal for a protein aggregation clock is one of the more innovative ideas circulating in the literature toward understanding how to measure biological aging. However, translation into a diagnostic tool lies some distance away, though it represents an essential first step in the long-term study of protein aggregation in connection with age-related disorders. Through interdisciplinary collaborative efforts, enabled by new technologies, they move the field forward toward innovation to ensure enhanced quality of life and longer life expectancy for aging populations.
In their effort to better understand the protein aggregation clock, Dormann and Lemke respect the complexity and variability in all aspects of aging. They stress that genetic, environmental, and lifestyle factors influence aging in very complex ways. While protein aggregation is one important marker, it represents only one feature in the landscape of cellular aging. How such other biological processes interplay and interact and hence possibly influence the IDP aggregation should be further pursued in future studies in order to present the global picture of the dynamics of aging.
Furthermore, a protein-aggregation clock is highly difficult to establish and hence needs stringent validation and optimization. Sensitivity and specificity of clinical utility call for technological advances able to correctly detect and quantify protein aggregates in many cell types and tissues. Standardization of such methodologies will be imperative to ensure reproducibility and reliability in diverse clinical settings.
Beyond the potential diagnostics it holds for age-related diseases, the protein aggregation clock could also help drive forward personalized medicine approaches within geriatric care. It would enable healthcare providers, who are in a better position to demarcate preventive strategies and interventions for those at a higher risk of developing age-related diseases at an early stage of life, to do so much earlier than is currently possible. This pre-emptive approach would thus improve not only individual health outcomes but also set a reduced socioeconomic burden associated with managing chronic diseases in aging populations.
Dormann and Lemke’s visionary approach to the incorporation of IDP aggregation into biological aging clocks underlines the radical potential of protein-centric perspectives in healthcare.provided further work goes into refining and expanding on this study, scientists will stand a good chance to pick novel information about the biology of aging and therapeutic strategies that may redefine healthy aging in coming decades. It can give them a view of the future: one in which aging is better understood, managed, and perhaps even reversed at the molecular level through their work with collaborative efforts and sustained innovation.
Q6. A protein aggregation clock also raises some very interesting, deep questions about what fundamental aging actually is. For instance, those researcher individuals working on protein dynamics and aggregation as key indicators might ultimately uncover mechanisms underlying cellular senescence and functional decline over time. Such deeper understanding may open new therapeutic targets to/modalities that intervene in protein homeostasis, retaining cellular function throughout life, and thus extend healthspan—the period of life free from chronic diseases and disabilities—and improve the quality of life for aging populations worldwide.
A protein aggregation clock would transcend its potential influence on individual health to that of high potential for public health strategies and health care policy. An increase in the human lifespan observed worldwide raises an urgent need for innovative approaches to allow for treatments against age-related diseases but also against their onset and impact on society. Health systems could better allocate resources toward preventive care and targeted interventions at the earlier biomarkers, such as the IDP aggregation, are identified, which could reduce the cost of care associated with healthcare while improving health outcomes in older adults.
The protein aggregation clock is still an infant concept, but laying a promising path to turn a conventional perspective in understanding and managing aging conditions by Dormann and Lemke for this groundwork. By the combination of interdisciplinary efforts in proteins and technological progress, work on protein biology has positioned itself to hold a commanding position redefining aging as a manageable process and possibly modifiable. As this field evolves further, the probability that a future where proactive strategies and tailored interventions meet aging comes closer to being a healthier, more resilient aging population in the years to come.
Source: SciTechDaily
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