The 100 Most Cited Publications in Aging Research: A Bibliometric Analysis

The 100 A Bibliometric ABSTRACT Aim: The basic aim of this analysis was to evaluate the 100 most cited publications in aging research. Methods: On January 17, 2021 Web of Science Core Collection database was searched for aging research publications. The studied parameter includes; publication year, authorship, publication type, keywords, journal name, institution, country, and visualization mapping. HistCite TM application for citation analysis and VOSviewer software was used for visualization mapping. Results: The top 100 most cited papers were published in 52 journals, authored by 537 authors. The most cited paper was “The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease,” which received 6039 citations (2013 average citations per year). Nature was the most attractive journal (n=13). Aging was the most dominant used keyword. The maximum number of papers were published in 2005 (n=8). Harvard University was the leading institute (n=13), while the United States of America (USA) was the most productive country (n=76). Conclusion: The highly cited papers were published in developed countries, and no study was published in low-income countries.


INTRODUCTION
Biological aging (evry living organism) involves a broad range of life changes that negatively impact all fundamental biological processes and ultimately lead to loss of organismal homeostasis and eventually death [1,2]. Human aging (related to human lives) annexes the macroscopic changes, including grinding of the skin, wrinkling, loss of muscle, and physical weakness. They are more vulnerable to a wide range of diseases when individuals get older. In particular, cardiac diseases, cancer, and stroke are the most common age-related disorders, including chronic lower respiratory disorders, type 2 diabetes, and neurodegeneration, representing the leading cause of death among the aged [1,3]. The burden of human aging in all nations worldwide is enormous social, medical, and economical. It is crucial and urgent to develop effective interventions to ensure healthy aging [4]. Age-dependent molecular damage accumulates lower DNA or protein stability, energy production, utilization failure, and homeostasis disruption leading to structural and functional decline. Mutations that offer an overall health benefit over a lifetime of the organism are also expected to increase the population frequency, although their phenotypic action in older ages is detrimental [1,2]. The evolutionary aging theory predicts that the average life span is higher in organisms where fertility increases with age, and the intrinsic rate of aging develops in response to extrinsic hazards [5].
Model organisms were used extensively to discover the retained aging pathways and assess interventions that improve longevity and aging. Laboratory mice, insects, and rats are commonly used in aging research in laboratory mice with strong genetic backgrounds, short life, ease of feeding, defined genetic manipulation, and environmental risks [4]. All living things age somehow, and it has proven surprisingly difficult to explain why despite years of research [6,7]. Why, for example, do our repair mechanisms appear to degrade with age, resulting in the loss of youth natural resilience to minor physical injury and physical stress [8]? The enzyme telomerase is a hot topic in ageing research at the moment, as it is responsible for maintaining the protective "seal" at the end of each chromosome [9]. Telomeres are the names given to these ends [10], and they prevent chromosomes from fusing and causing abnormalities and protecting the chromosome ends from being nibbled away by cell enzymes [7,10,11]. Chromosomes are extremely valuable and must last a lifetime [12]. They replicate themselves with each cell division, but this also means that any damage sustained during the division process is passed on to the new cells [13]. The lives of animals are limited from a few weeks (Drosophila melanogaster, Caenorhabditis elegans, and Daphnia longispina) to centuries (Arctica islandica) (Figure 1). Lifespan extension has been of interest for a long time, but longevity mechanisms remain mostly unknown. Invertebrates such as fruit flies or nematodes (fish and mice) with relatively short lifespans are excellent models to study longevity mechanisms. Interestingly, new animal models have been applied for longevity studies under technological developments such as Next-Generation sequencing (NGS) [14]. Bibliometrics analyses; a series of written publications, including journals, books, and scientific publications, using statistical and mathematical tools [15]. It evaluates quantitative research academic output and provides evidence of financing [16]. Bibliometric analysis provides insight into a subject, field, or discipline. It assesses authors, institutions, and countries performance by mapping the structure and dynamics of disciplines utilizing databases [17]. A map understands the information produced in a given field and helps develop public health policies by monitoring its development [15]. Social network analysis for scientific collaboration and co-citation relations is used in bibliometric studies [18]. The international citation indexes, Science Citation Index Expanded (SCI-E), Social Sciences Citation Index (SSCI), and Arts and science quote index are the most critical data sources (A & HCI). The Web of Science Core Collection (WoSCC) database provides access to these indexes [15,[19][20]. Thus, the current study was conducted to identify and characterize the 100 most cited publications in aging research.

METHODS
On January 17, 2021 the WoSCC database was searched using the search keywords ("Aging" OR "Ageing") in title field without restrictions. The 100 most cited papers were included based on the number of citations (Figure 2). The following data were extracted; year of publications, authors, type of publications, journals name, frequently used keywords, institutions, and countries. The data were exported in to HistCite TM and VOSviewer software for windows for citations count and network visualization mapping respectively. The retrieved data were plotted for co-authorship countries and, co-occurrence author keywords. In this study, no human or animal subjects were involved directly, therefore no ethical consideration was needed.

RESULTS
The top 100 most cited papers were published in 52 journals with 6716 cited references, 407 keywords, and 537 authors. Among them, 63 were research articles (15996 global citations), and 29 were reviews articles (53923 global citations) ( Table 1). The most cited paper was "The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer'  Table 2). The most productive year was 2005 (n=8), while the most cited year was 2011 (n=20041 global citations), as shown in Figure 3A and 3B, respectively. The leading country in aging research was the        United States of America (USA) with 76 publications ( Table 3). Aging (n=78), Ageing (n=22), and Disease (n=17) were the most frequently used keywords ( Table 4). The most prolific author was Phelps CH (n=5) ( Table 5). The most active institute was Harvard University, USA (n=13) ( Table 6). Nature was the most attractive journal (n=13) ( Table 7).

Co-authorship and Country
The co-authorship and country mapping is presented in Figure 4. The minimum number of the document per country was set at 2. Of the 22 countries, 15 were included for visualization after network mapping. The USA had the highest total link strength (TLS) of 38, followed by England (TLS=24), and Germany (TLS=25).

Co-occurrences and Author Keywords
The minimum number of a keyword occurrence was fixed at 1. Minimum items included in a cluster were fixed at 5. Based on TLS, aging and dementia were the most widely used author keywords (TLS=49), and (TLS=16) respectively as shown in Figure 5.

DISCUSSION
Bibliometric type studies are of great interest, providing an overview of the scientific published literature and other important parameters [22]. The number of bibliometric studies has been increased over the years [23]. This is the first comprehensive bibliometric analysis summarizing several features of the most influential studies on aging. Analysis of most cited studies on aging may be worthwhile to keep the young researchers and clinicians abreast of traditional knowledge. It may help clinicians, nutritionists and policymakers to decide based on results from influential previous studies.
Aging is an irreversible phenomenon that leaves multiple effects on the human body. Generally, it weakens muscles and all the body functions, leading to certain complications that ultimately burden the health system. In order to overview the research trends and most commonly addressed issues, the bibliometric is the most helpful strategy to reach the hot spot and analyze the research conducted in the field. By this, the researcher can easily identify the multiple studies on the same topic, select the best one, and summarize the best available evidence after critical analysis. This bibliometric study has selected 100 publications/papers out of 131,652 on aging published during the last century, i.e., from 1900-2021. During this period, the citation and publication pattern is not uniform. It keeps changing from year to year.
All the included publications in this study were published in English, and 63% were research articles while 29% reviews, 4% proceeding papers, 3% were book chapters. This trend . There are 7 clusters formed; cluster 1 red color (19 items), cluster 2 green color (13 items), cluster 3 blue color (11 items), cluster 4 yellow color (9 items), cluster 5 purple color (8 items), cluster 6 light blue (8 items), and cluster 7 orange color (5 items) illustrates that English is a widely used language to exchange scientific findings, and a majority of the scientific results on aging are being published resulting from experimental work though the share of review and other articles are also countable. The most frequently used keywords and research areas linked with aging studies reflect the research focus.
More research is needed to be carried out in this field, and scientists, especially from developing countries, should be encouraged to conduct research and share the findings in peerreviewed journals. Moreover, researchers and clinicians need to use the evidence summaries in clinical practices and update and develop new summaries based on their practices to use these approaches as well.

LIMITATIONS
This study has several limitations; a) a single database (WoSCC) was utilized; b) The citations count was based on WoSCC; c) The use of other databases like like Scopus and Google Scholar may alter the citations count or publications frequency.

CONCLUSION
This study provides a detailed, comprehensive overview of aging research. The USA was ranked the most productive and active country. The finding from 100 most cited publications in aging research may help the researchers, policymakers, and funding agencies for future research directions and hotspots. Low-and middle-income countries need to be supported through funding and by collaborating with them to upgrade the technical skills of researchers and clinicians.