Establishing a Comprehensive Anti-aging Research Center: Experiences and Challenges

Introduction: Age-related diseases have become the leading causes of morbidity and mortality worldwide. Anti-aging researches both at the population and individual levels are still urgently needed. Establishing comprehensive anti-aging research centers is crucial to advancing anti-aging researches. However, few studies have shown guidelines for establishing a comprehensive anti-aging research center. We aim to describe the establishment of a comprehensive anti-aging center, summarize the initial experiences, and discuss limitations, strengths and challenges. Methods: The establishment contains three phases (from October, 2017 to January, 2020), the rst phase is assessing the need for anti-aging research by reviewing relevant literatures and investigating the elderly population. The second phase is interpreting the aging-related policies by searching and analyzing China's aging-related policies in recent years on government websites. The third phase is completing the protocol of establishing the center, raising funds for the establishment of the center and selecting the adequate equipment. Results: In phase one, we nd improving strategies at the population and individual levels are still needed. Through establishing elderly cohort, we nd that many elderly people are with high risk factors of aging. In phase two, we nd many age-related policies have been unveiled. In phase three, we complete the protocol of establishing the center based on the results of phase one and two. We also have raised funds and selected equipment for the center. Conclusion: With limited guideline for establishing a comprehensive anti-aging research center, the experience in this paper might help other institutions to build anti-aging research center or program.


Introduction
Population aging is one of the most important global social trends in the 21st century. The most immediate result of aging is an increase in the incidence of age-related diseases 1 . It is well known that chronic non-communicable diseases have been the major contributors to the disease burden, among which age-related diseases such as diabetes, cardiovascular disease, and cancer diseases have become the leading causes of morbidity and mortality worldwide [2][3][4][5][6][7][8][9] . Moreover, these diseases could not only affect the life quality of the elderly, but also the family members who take care them 10 . So how to prevent the age-related diseases and how can people achieve the condition of healthy aging? Further exploration of improving anti-aging strategies is important for human health.
At present, multiple anti-aging researches are in development, and some of them have shown considerable promise for slowing down aging or reducing the incidence of age-related diseases. It appears that enhancing autophagy 11,12 , eliminating senescent cell 13,14 , transfusing plasma from young individuals 15,16 , and stem cell therapy 17,18 are promising interventions to help individuals get conditions of healthy aging. However, many of them are pre-clinical studies which still need critical assessment in clinical trials to con rm their e cacy. Moreover, some interventions that could be very useful in clinical settings might not even reduce the risk of age-related diseases at the population level. This may because implementing such interventions at population level should consider not only biological and medical factors but also socioeconomic and political factors. There is no doubt that interventions aimed at reducing the risk of diseases are superior to therapeutic methods. And it is cheaper and easier to prevent diseases through health strategies and policies. So we aim to establish a comprehensive anti-aging research center focusing on the anti-aging programs/researches both at the population and individual levels. In this paper, we will describe the establishment of this center, summarize the initial experiences, and discuss limitations, strengths, and challenges.

Methods
This comprehensive anti-aging research center was rst proposed in October, 2017, and preliminarily completed in January, 2020. In the development of any research center, the most important starting point is to de ne the center's mission. The mission statement of this center is to slow down aging, reduce the incidence of age-related diseases, and help the elderly maintaining a better physical and mental health.
The establishment of the program is completed in three phases. The rst phase: assessing the anti-aging need; the second phase: interpreting the aging-related policies; the third phase: completing the protocol for establishing the anti-aging research center. A speci c committee composed of the big data evidencebased decision-making department (department A), the policy transformation department (department B), and the experimental and clinical research department (department C) is assigned the above missions Investigating: Establish the elderly cohort to collect self-assessment information of the elderly's health through questionnaires. The information include: age, sex, BMI, defecation, bradymasesis, sedentariness, physical exercise, sleep, chronic disease, smoking and drinking. The inclusion criteria: 1) 60-90 years old; 2) informed consent. The exclusion criteria: the elderly who can't complete the questionnaire.

Execution of the Phase 1
Reviewing: According to review and summarize researches of anti-aging in databases. We nd that the anti-aging interventions can be divided into three categories depending on how they are implemented: drug interventions, non-drug interventions, and other interventions (Table 1). For drug interventions and other interventions, the main bene ts might include opportunities to extend human life cycle, reduction of age-related diseases, and improving the quality of life. Moreover, these results have been mostly veri ed by animal evidence-based clinical studies. However, when it comes to promotion at the population level, drug interventions still have the following problems: lack of human clinical trials, high costs of some drugs, and ethical issues. For non-drug interventions, they are cheaper and easier to operate, as they are non-invasive and appear to have minimal side effects. Moreover, these interventions can be used not only as important applications of anti-aging interventions at the individual level, but also to bring greater bene ts to public health strategies at population-level. However, these non-drug interventions lack evidence of large-scale clinical trials. Stem cell therapy and plasma therapy are two "special drug interventions", they require clinical trials for safety and e cacy. Therefore, given the multifactorial nature of aging, it is urgently important to develop anti-aging programs based on integrating the above interventions, which is also conducive to the formulation of the most appropriate anti-aging interventions at the population and individual level.  Execution of the Phase 2

Policies
Since the Chinese government has initiated the building of a healthy China and a community with shared future for mankind, a number of policies to deal with aging has been unveiled. Most recently, the government unveiled a medium and long-term plan for responding proactively to population aging. The plan requires establishing the basic institutional framework for tracking population aging by 2022 19 . By the middle of the century, a mature institutional arrangement that meets the needs of a great modern socialist country should be put into place. It deploys the speci c task of coping with the aging population from ve aspects. Firstly, it calls for improving the national income distribution system, steadily increasing the pension reserves and establish a fairer and more sustainable social security system. Secondly, it requires improving the quality of new members of the labor force, establishing a lifelong learning system for senior citizens, and striving to achieve fuller employment and create better quality jobs. Thirdly, according to the plan, a high-quality health service system including health education, disease prevention and treatment, rehabilitation nursing, long-term nursing and hospice care should be established. Fourthly, the plan also values the application of technology in responding to population aging including strengthening the development of assistive technologies for senior citizens. Fifthly, it also calls for fostering a social environment in which senior citizens are respected, cared for, and live happily in their later years. The legal system will be improved to protect the lawful rights and interests of senior citizens 19 . Therefore, the importance to address the challenge of aging has been increasingly recognized by the Chinese government, and the anti-aging researches will be actively supported.

Discussion
In this paper, we report for the rst time on the steps of starting up a comprehensive anti-aging research center. This might provide reference value for the construction of other anti-aging center. The establishment of our center is still in progress and will continue to be improved in the following work.
Although the problem of aging is common all over the world, it is particularly pressing for China. The absolute number of elderly people (≥ 65 years old) in China is the largest in the world with 167 million, accounting for 12% of the total population in 2019, and will rise to almost 400 million by 2050, accounting for 26% of the total population 20 . Meanwhile, China has increasingly recognized the vital need to address the aging challenge, and has proactively proposed the "Healthy China 2030" plan. Healthy ageing is not only the absence of disease, but also the maintenance of functional ability throughout the life.
Our center is established to respond to the increasingly serious crisis of aging and age-related diseases worldwide. One of the focuses of the center is to carry out anti-aging research at the population level. At the same time, we also focus on formulating precise anti-aging programs for individuals. Currently, physical exercise and caloric restriction are the two main interventions against aging at the population level 21,22 . But these population-level interventions haven't been universally acknowledged as effective in humans, factors like the genetic background and the phase of life when it occurs might also in uence the outcomes [23][24][25][26][27] . For example, regular physical activity is less effective for individuals with physical disability, especially for those with low income. Another example is restricting calories in the elderly, which can lead to loss of muscle mass 22 . Moreover, the elderly might confront different age-related health problems, just as the results of our results. So simply relying on physical exercise and caloric restriction to improve the anti-aging effect at the population level is not enough. Interventions at the individual level might be useful in population sub-groups when the population-level interventions are not feasible or controversial. Therefore, more well-conducted randomized controlled trials are still needed to assess the effect of these anti-aging strategies.
When launching a research center, especially when the research theme of the center are associated with many disciplines, it should be implemented by a well-structured and multidisciplinary team. In this center, our team includes not only experts in the eld of aging, but also experts in statistics, public health, and policy transformation. Meanwhile, we cooperate with medical teams in hospitals and community health service centers to carry out comprehensive anti-aging research at the population level. The experience in the establishment of a center is of great help for other centers. Although programs/ researches of antiaging have become the focus of researches, there is no standard guideline for establishing anti-aging research centers. So the above described method is suggested. Moreover, we also compare the establishing guidelines with other kind centers. For example, a study 28 reported a comprehensive six-step for the establishment of a new extracorporeal membrane oxygenation (ECMO) center: planning, developing, implementing, sustaining, evaluating, and moving forward. Recently, Assy J et al. 29 established a ECMO center with limited resources by following the six-step guidance. This showed the importance of developing guidelines for the establishment of speci c center. There are many similarities between their steps and ours. For example, their rst step is "planning", which includes the identi cation of key personnel, the assessment of needs, and the development of a strategic plan; Their second step is "developing", which requirs the clear designation of human and organizational resources, as well as the acquisition of appropriate equipment. The information contained in these steps is also re ected in our construction process. However, since they are the centers of ECMO, and our center covers a variety of program/researches related to anti-aging, their guidelines for implementing, sustaining, and evaluating are different from ours.
This study also have some limitations. Firstly, since the establishment of this research center has just been completed, and the anti-aging programs/researches have just started, the value of the center cannot be evaluated by the results of these anti-aging studies. In addition, there may be other di culties or problems in the process of conducting each anti-aging programs, such as the e ciency of policy transformation, the evaluation and the promotion degree of the research results, which all need to be actively dealt with in the following work.

Conclusion
With limited guideline for establishing a comprehensive anti-aging research center, the experience in this paper might help other institutions to build their own anti-aging research center or program.

Declarations
Ethics approval and consent to participate The researches involved in the establishment of the center have been approved by the Ethics Committee of Shanghai East Hospital, Tongji University School of Medicine. All participants were informed consent.

Availability of data and material
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. The ow chart