The challenge of the aging society and potential solutions

Some international policy documents and programs are less supportive of such research, still some support may be derived from them. Yet it may be argued that it is only by prevention and treatment of the underlying aging processes, thanks to biomedical research and development, that the goal of a significant reduction of mortality from non-communicable age-related diseases could ever be achieved.

The SDG3 Clause 3. Yet, in fact, aging-related morbidity is an ever-increasing concern for the developing countries, while their gerontological and geriatric infrastructure is far less advanced than in the developed countries [ 10 ]. The introduction of enhanced science-based medical evaluation criteria for the aged may contribute to the development of gerontological research and practice capabilities in the developing countries, also as a part of the SDG framework. At the national level, for over two decades, the regulatory authorities of the EU, US and Japan have struggled to obtain special consideration for older patients in the research, development and application of medical treatments, to involve elderly subjects in all clinical trials, and to establish criteria for treatment efficacy and safety specifically for the elderly.

In the EU, in the past years, the European Medicines Agency EMA has undertaken several programmatic initiatives to include the elderly into clinical trials and to develop the relevant diagnostic, inclusion, efficacy and safety criteria http: Yet, subsequent reports revealed that those needs, in many cases, are not sufficiently addressed [ 12 ]. There have been also continuous efforts by the EMA to develop the diagnostic criteria for general age-related frailty as a common determinant of age-related diseases and disabilities.

Apparently, these documents are still in preparation [ 15 ]. The need for the inclusion of older subjects in all clinical trials and the necessity for devising specific criteria for their diagnostic and therapeutic assessment are recognized. Yet, apparently, this directive has not been satisfactorily accomplished. For example, there is no mandatory inclusion of elderly subjects in NIH trials, unlike children, women and minorities https: Nonetheless, an important development recently occurred with the FDA. The study, perhaps for the first time, is approved for an intervention into the aging process in order to reduce aging-related multimorbidity.

Yet, crucially, there is no agreed measurable clinical definition and criteria for multimorbidity either [ 17 , 18 ]. The developments of agreed and strict methodologies to evaluate either degenerative aging itself or age-related multimorbidity or frailty, as treatable medical conditions, still appear to be desirable tasks for the future, for the EMA, FDA and other national regulatory agencies. However, in order to arrive at reliable diagnostic definitions, the common functional frailty assessments may need to be supplemented in a larger scope with assessments of biomarkers of the aging process, in correlation with each other, thus reinforcing the diagnostic and predictive capacity of the combined functional and biological indicators.

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Currently, functional assessments dominate the evaluations of frailty http: It may be seen that biological markers of aging are assigned little significance in such scores. However, in order to provide a reliable science-based proxy or indication for the aging process, it appears necessary to include more parameters measuring this process at its fundamental biological level. The energy metabolism measurements may supplement molecular-biological measurements that are commonly employed in the research of biomarkers of aging e.

The addition of biological indicators to frailty assessments may provide advanced diagnostic capabilities. Yet, in many cases, age-related frailty is not considered among the clinical assessments of the aged at all, even based on only functional parameters. The addition of biomedical tests on aging to the ICF may be parallel to an addition of some clinically applicable, science-based and practical definitions, criteria or classification of aging or senility within the ICD and GSAP.

It may be possible to emphasize the clinical significance of the aging process on all the fronts at once. Yet several critical methodological challenges may arise in developing commonly acceptable diagnostic definitions and criteria for degenerative aging.


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This distinction may have major implications for intervention, respectively implying a curative approach to the already manifest state of degeneration a late stage intervention as opposed to a preventive approach to block a process leading to degeneration an early stage intervention.

Yet, many questions remain with such a definition. Obviously, not every time-related change leads to degeneration and disease, and some aging-related changes may be beneficial for the person e. Obviously also, many changes leading to age-related degeneration begin at conception, and may be necessary concomitants of the processes of growth and development.

Then for which processes and at which stages is intervention warranted? Several sets of such candidate processes have been proposed [ 27 - 29 ], yet there is still little empirical evidence that intervention into them will have clinical benefits. The potential interrelation and regulation of these various processes are also uncertain. A more thorough, quantitative and formal understanding of old-age degeneration frailty as a physiological state is required as well. Should it be measured as a lack of function and adaptation to the environment, an impairment of homeostatic or homeodynamic stability?

Each of these options would raise a host of questions of its own, whose mere mentioning would go far beyond the scope of this policy review. To provide evidence-based answers to those questions, vast empirical and theoretical research yet appears to be needed to establish diverse age-related changes as predictors of adverse age-related outcomes such as multi-morbidity and mortality as well as evaluate the effects of various preventive and curative treatments on those outcomes.

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Based on such data, better formal, clinically applicable models of degenerative aging as a process and as a state can be developed. It is hoped that the present work will contribute to raising the demand for more such research. Just a few particular challenges may be mentioned here for the development of diagnostic and treatment criteria for degenerative aging. These can be tentatively classified as follows: This could also be the putative priority order at which the problems can be tackled.

It must be reemphasized that these propositions are only intended to stimulate academic and policy discussion. These may include the questions above. There is a need to precisely define measurable clinical end points, demonstrating evidential clinical benefits [ 32 , 33 ], especially for the reduction of age-related multimorbidity. The combination of structural biological and functional behavioral parameters may increase diagnostic capabilities. The clinical benefits need to be evaluated in the primary target population - the older frail persons, rather than the younger and healthier ones who may exhibit entirely different biological responses [ 34 ].

The clinical criteria and biomarkers, as well as resources available to the organism, need to be considered for the long term [ 35 ]. Thanks to long-term evaluation it may be possible to control for effects of over-stimulation, as well as rule out transient compensatory and psychosomatic effects and seeming short-term benefits that may arrive at the expense of long-term deterioration.

Moreover, these criteria may not necessarily be chemical and biological, but can also be physical, in particular as relates to various resuscitation technologies as applied to the elderly, such as hypothermia and suspended animation [ 39 ], oxygenation and energy metabolism [ 40 ], electromagnetic stimulation [ 41 ]. Social engagement and psychological motivation criteria also need to be added. Individual biomarkers may not be indicative of the process or state of degeneration, and need to be considered in combinations, or ideally in a systemic balanced way - otherwise interventions on particular biomarkers and pathways may exacerbate other biomarkers and pathways, and disrupt the system as a whole.

The general methodology for the evaluation of the effects of multiple risk factors including biomarkers of aging on multiple age-related diseases multimorbidity need to be improved, to allow the evaluation of non-linear, cumulative or synergistic effects [ 31 , 42 , 43 ]. Particular batteries of assays are usually related and potentially biased to particular theories, research agendas, academic schools and commercial interests.

There is an apparent need to allow pluralism of investigation, discovery and application, while maintaining standards of the scientific method. Consensus standards often emerge as a result of data-sharing [ 44 ], which may become a practical challenge of its own. Costs of biomarkers assays may become prohibitive or even impractical for use by most people in the world.

There is a need to focus on such biomarkers and functional assays that may be most cost-effective, especially those that are already routinely used in clinical practice, while still encouraging the development of more sophisticated assays, that may become more accessible in time, and specifically devising means to increase their accessibility [ 45 ].

All these issues must become a subject of massive and pluralistic consultation, involving scientists, policy makers and other stakeholders. Thanks to such a consultation it may be possible to develop agreeable scientific clinical criteria for degenerative aging that could improve diagnostic capabilities and allow better informed clinical decisions, as well as stimulate further research and development of effective, evidence-based therapies treating the underlying processes of aging-related diseases rather than their particular symptoms.

National Center for Biotechnology Information , U. Journal List Aging Dis v. Published online Oct 1. Author information Article notes Copyright and License information Disclaimer. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. This article has been cited by other articles in PMC. Abstract It is becoming increasingly clear that in order to accomplish healthy longevity for the population, there is an urgent need for the research and development of effective therapies against degenerative aging processes underlying major aging-related diseases, including heart disease, neurodegenerative diseases, type 2 diabetes, cancer, pulmonary obstructive diseases, as well as aging-related complications and susceptibilities of infectious communicable diseases.

Establishing definitions 1 Establishing basic terms and definitions These may include the questions above. Minimizing confounding factors 1 Focus on older persons The clinical benefits need to be evaluated in the primary target population - the older frail persons, rather than the younger and healthier ones who may exhibit entirely different biological responses [ 34 ].


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  5. Improving practical utility 1 Pluralism and rigor Particular batteries of assays are usually related and potentially biased to particular theories, research agendas, academic schools and commercial interests. The critical need to promote research of aging and aging-related diseases to improve health and longevity of the elderly population. Aging Dis , 6 1: The demographic and biomedical case for late-life interventions in aging.

    Sci Transl Med , 2 Substantial health and economic returns from delayed aging may warrant a new focus for medical research. Health Aff , 32 Nature , Classifying aging as a disease in the context of ICD Front Genet , 6: National Center for Biotechnology Information , U. Journal List Aging Dis v.

    Published online Dec Kunlin Jin , 1, 2 James W. Find articles by Kunlin Jin.

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    This article has been cited by other articles in PMC. Abstract Due to the aging of the global population and the derivative increase in aging-related non-communicable diseases and their economic burden, there is an urgent need to promote research on aging and aging-related diseases as a way to improve healthy and productive longevity for the elderly population. The challenge of the aging society and potential solutions Over the past decades, the average life expectancy has increased globally, reaching a world-wide average of about 70 years in 6 years longer than in and around 80 in the developed countries compared to about 50 years in the developed countries in the early 20 th century.

    Although people might want to participate in the workforce for a longer time, they may not be able to, due to cognitive and physical decline. Moreover, they are likely to decrease susceptibility of the elderly also to communicable diseases due to improvements in immunity [ 29 ]. Ensuring a significant increase of governmental and non-governmental funding for goal-directed translational research in preventing the degenerative aging processes, and the associated chronic non-communicable diseases and disabilities, and for extending healthy and productive life, during the entire life course.

    Dedicating a specific percentage of the profits of commercial pharmacological, biotechnology and medical technology companies to such research and development.

    Regulatory and policy frameworks

    Developing and adopting legal and regulatory frameworks that give incentives for goal-directed research and development designed to specifically address the development, registration, administration and accessibility of drugs, medical technologies and other therapies that will ameliorate the aging processes and associated diseases and extend healthy life. Developing criteria for efficacy and safety of geroprotective therapies.

    Facilitating in silico and animal testing, and ethical safety-enhanced human testing of such therapies. Deploying and ensuring geroprotective therapies in the status of adjuvant and life-extending therapies. Providing a shortened approval pathway for therapies with high level of efficacy evidence in preclinical and early clinical trials, as well as in cases of advanced degenerative and seemingly futile conditions.

    Granting a special recognition, status and benefits to commercial and public entities engaged is such research and development. Establishing and expanding national and international coordination and consultation structures, programs and institutions to steer promotion of research, development and education on the biology of aging and associated diseases and the development of clinical guidelines to modulate the aging processes and associated aging-related diseases and to extend the healthy and productive lifespan for the population.

    Establishing Biogerontology specialty and courses in Biogerontology as a common part of university curriculum.

    Developing and disseminating geroprotective regiments, based on the best available evidence, as part of authoritative health recommendations. Establishing cooperative centers of excellence for fundamental, translational and applied studies, alongside centers for strategic analysis, forecast, education and policy development on aging and longevity research, at academic institutes and various governmental and supra-governmental agencies. A Call to Action. Global and regional mortality from causes of death for 20 age groups in and A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, — a systematic analysis for the Global Burden of Disease Study The Future of Aging: Pathways to Human Life Extension.

    The hallmarks of aging. Substantial health and economic returns from delayed aging may warrant a new focus for medical research. The demographic and biomedical case for late-life interventions in agin g. The sirtuin SIRT6 regulates lifespan in male mice.

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    Extending life using tissue and organ replacement. The prolongation of the lifespan of rats by repeated oral administration of [60] fullerene. Oxygen gas-filled microparticles provide intravenous oxygen delivery.