The Effects of Physical Activity on the Aging of Circulating Immune Cells in Humans: A Systematic Review
Round 1
Reviewer 1 Report
Comments
The systematic review by Lara Brauer et al. entitled 'The effects of physical activity on cellular senescence of leucocyte subpopulations’ deals with broad subject of immune system and physical activity. While these immune cells are not sedentary in adult vs elderly population so its difficult to analyze and compare. Its well known that the immune system of elderly people are altered due to the aging process including replicative senescence of cells. Authors attempt to put these two subjects together to view the beneficial effects of PA in restoring or protecting immune cells from senescence is commendable.
The studies selected on the basis of inclusion and exclusion criteria of this study show variable parameters as well as training methods and sample collection is at very different time points. So in my opinion it’s very difficult to compare these studies with each other and conclude. For example, we can not compare 6 months to 6-hour changes. Moreover, it would be helpful if authors are able to add population diversity and zones where these studies have been conducted. It will give new information about the effect of PA in the immune system of diverse people.
Authors mention that some of the articles were excluded due to inaccessibility. This seems a drawback of this study because you can ask authors for preprint if study is in your inclusion criteria.
Authors need to change the title. The title of the review does not match with the content. It would be better to write immune cells rather than leucocyte subpopulation.
Please correct sentence line 19 to 20
In line 97 it would be better if the paragraph starts with senescence and its definition. Authors start defining senescence in the middle of the paragraph.
Introduction of the review is not focused, need update.
In some of the sentences, the authors want to talk about vaccines efficacy in elderly people which deviates from the subject. If authors want to keep these subjects then they need to correlate them with the main subject of the review. In my opinion review should be focused on the main subject of the review.
Discussion is nicely written.
Author Response
Reviewer 1
- The studies selected on the basis of inclusion and exclusion criteria of this study show variable parameters as well as training methods and sample collection is at very different time points. So in my opinion it’s very difficult to compare these studies with each other and conclude. For example, we can not compare 6 months to 6-hour changes. Moreover, it would be helpful if authors are able to add population diversity and zones where these studies have been conducted. It will give new information about the effect of PA in the immune system of diverse people.
Our response: Thank you for the important comment from reviewer 1. It is true that we included a wide range of training methods due to the influence of acute and long-term effects of training. These are indeed difficult to compare, but we have differentiated this in the results section and discussion. However, we have once again made it clear in the discussion as a limitation. We have once again looked at the included studies on the topic of diversity of the subjects. Due to the limited data, we do not consider it is permissible to distinguish between ethnic and zone-specific subgroups. Further studies are needed for such investigations. We thank you for your comments.
- Authors mention that some of the articles were excluded due to inaccessibility. This seems a drawback of this study because you can ask authors for preprint if study is in your inclusion criteria.
Our response: We agree with the reviewer. We have taken this into account as a limitation in the discussion (lines 872-874).
- Authors need to change the title. The title of the review does not match with the content. It would be better to write immune cells rather than leucocyte subpopulation.
Our response: We changed the title accordingly.
- Please correct sentence line 19 to 20
Our response: Corrected.
- In line 97 it would be better if the paragraph starts with senescence and its definition. Authors start defining senescence in the middle of the paragraph.
Our response: Thank you for this comment. We have revised the introduction section more comprehensively and focused so that the definition has moved closer to the beginning.
- Introduction of the review is not focused, need update.
Our response: The introduction has been revised and information that does not directly address the topic has been removed. Thank you for this comment, which has sharpened the introduction.
- In some of the sentences, the authors want to talk about vaccines efficacy in elderly people which deviates from the subject. If authors want to keep these subjects then they need to correlate them with the main subject of the review. In my opinion review should be focused on the main subject of the review.
Our response: We thank the reviewer for the comment. We have removed the passages on vaccinations and also focused text passages in other places on the main subject of the review.
Reviewer 2 Report
Dear authors,
this is an interesting and well-written paper with sound methodology. The results are based on 10 meticulously selected papers, allowing conclusions.
I only have very minor comments, mostly typos, terminology and small inaccuracies in formulating sentences.
Some examples (not exhaustive):
In the exclusion criteria table (Table 3): What do you mean by 'foetal subjects'? Pediatric? AND 'Exclusively adolescents and adults (≤ 35 years)'? - you probably mean: ..adults ≤ 35 years OR ...'young' adults (≤ 35 years). Otherwise it reads '..adolescents and adults' in general.
Some of the criteria are capitalized, others are not. Would you consider having all alike?
Terminology: I am not sure if a 50 year old person should be described as elderly. Perhaps use a more neutral adjective, none at all, or just specify that you did not include the youngest groups where immune responses are not significantly affected yet. Is there an age cut-off where immunity is significantly altered? Why was the age 50 chosen? And exclusion is set to under 45. What about the age group 45-50? they are neither in the exclusion or inclusion. Would you consider a more precise explanation? Also, several places in the text refer to 'studies including elderly subjects', 'older adults'.. Again this is an imprecise description. See also Table 7 in regard to this. If the authors of the papers describe their subjects in this way, I agree that literal description can be chosen, otherwise, the authors themselves may not agree that their subjects were 'old', 'elderly' etc.
Some minor typos/not well-structured sentences: E.g. 'However, elite athletes, who sustain the highest possible exercise levels, usually live as well considerably longer than the general population'.. (do you mean 'also' (instead of 'as well') - .. athletes also usually live considerably longer..
'...were examined in all studies, despite of Dinh et al..' Do you mean '..except Dinh..'?
Author Response
Reviewer 2
- In the exclusion criteria table (Table 3): What do you mean by 'foetal subjects'? Pediatric? AND 'Exclusively adolescents and adults (≤ 35 years)'? - you probably mean: ..adults ≤ 35 years OR ...'young' adults (≤ 35 years). Otherwise it reads '..adolescents and adults' in general.
Some of the criteria are capitalized, others are not. Would you consider having all alike?
Our response: Reviewer 2 is right. The information is somewhat confusing and inconsistent. We have aligned it and adjusted it accordingly in the revision. Due to the optimization of the inclusion criteria noted by reviewer 2, one study by Cosgrove et al. had to be excluded from the analysis.
- Terminology: I am not sure if a 50 year old person should be described as elderly. Perhaps use a more neutral adjective, none at all, or just specify that you did not include the youngest groups where immune responses are not significantly affected yet. Is there an age cut-off where immunity is significantly altered? Why was the age 50 chosen? And exclusion is set to under 45. What about the age group 45-50? they are neither in the exclusion or inclusion. Would you consider a more precise explanation? Also, several places in the text refer to 'studies including elderly subjects', 'older adults'.. Again this is an imprecise description. See also Table 7 in regard to this. If the authors of the papers describe their subjects in this way, I agree that literal description can be chosen, otherwise, the authors themselves may not agree that their subjects were 'old', 'elderly' etc.
Our response: In the sixth decade of life, the human immune system begins to undergo aging-related changes. Therefore, the age group of ≥ 50 years was included in this review. We specified this in our inclusion criteria. The term “elderly” may be misleading, so we specified that it is used in context of the aged immune system and not generally for the biological age of humans. In all of the included studies, subjects were described as “eldery”, “aged” or “old”, so we adopted this term for this review. For example, Pistillo et al. (2013) included in their aged group subjects from 50-64 years and described them as “older” or “aged”. For other literature regarding the topic of immunosenescence, the imprecise description “aged immune system” “older / elderly subjects” without explaining the explicit age range meant is used as well. We addressed this topic in the revised manuscript lines 233-240.
- Some minor typos/not well-structured sentences: E.g. 'However, elite athletes, who sustain the highest possible exercise levels, usually live as well considerably longer than the general population'.. (do you mean 'also' (instead of 'as well') - .. athletes also usually live considerably longer..
Our response: We agreed with the reviewer and corrected this sentence.
- '...were examined in all studies, despite of Dinh et al..' Do you mean '..except Dinh..'?
Our response: We corrected this mistake.
Round 2
Reviewer 1 Report
Accept.
