Liu, Y

Mukaetova-Ladinska, EB

Venneri, A

Frontiers in Aging Neuroscience

Brunel University Research Archive

TYPE EditorialPUBLISHED 20 February 2023DOI 10.3389/fnagi.2023.1140767OPEN ACCESSEDITED AND REVIEWED BYKristy A. Nielson,Marquette University, United States*CORRESPONDENCEElizabeta B. Mukaetova-Ladinskaeml12@le.ac.ukSPECIALTY SECTIONThis article was submitted toNeurocognitive Aging and Behavior,a section of the journalFrontiers in Aging NeuroscienceRECEIVED 09 January 2023ACCEPTED 31 January 2023PUBLISHED 20 February 2023CITATIONMukaetova-Ladinska EB, Liu Y and Venneri A(2023) Editorial: The impact of physical activityon white matter during healthy aging.Front. Aging Neurosci. 15:1140767.doi: 10.3389/fnagi.2023.1140767COPYRIGHT© 2023 Mukaetova-Ladinska, Liu and Venneri.This is an open-access article distributed underthe terms of the Creative Commons AttributionLicense (CC BY). The use, distribution orreproduction in other forums is permitted,provided the original author(s) and thecopyright owner(s) are credited and that theoriginal publication in this journal is cited, inaccordance with accepted academic practice.No use, distribution or reproduction ispermitted which does not comply with theseterms.Editorial: The impact of physicalactivity on white matter duringhealthy agingElizabeta B. Mukaetova-Ladinska1,2*, Yong Liu3 andAnnalena Venneri4,51School of Psychology and Visual Sciences, University of Leicester, Leicester, United Kingdom, 2TheEvington Centre, Leicestershire Partnership National Health Service Trust, Leicester, United Kingdom,3School of Artificial Intelligence, Beijing University of Posts and Telecommunications, Beijing, China,4Brunel University London, Uxbridge, United Kingdom, 5The University of Parma, Parma, ItalyKEYWORDSdementia, aging, white matter (WM), neuroprotection, physical activityEditorial on the Research TopicThe impact of physical activity on white matter during healthy agingThe benefits of physical activity are well-documented throughout the human lifespan.Both the current, UK Chief Medical Officer’s Physical Activity Guidelines (2019) and theU. S. Department of Health Human Services (2018) highlight their protective benefits ona range of many chronic conditions, such as coronary heart disease, obesity and type 2diabetes, mental health problems and social isolation. The guidelines recommend similarduration of physical activity for both younger and older adults. Namely, 150min (2.5 h) ofmoderate intensity activity (such as a brisk walk) or 75min of vigorous intensity activityweekly (i.e., running), along with a combination of moderate and vigorous activity, isrecommended to achieve greater benefits. Similar duration of regular physical activity isalso recommended by the World Health Organization with more benefits obtained whenthe cumulative time of physical activity is higher (300min per week or 5 h/weekly).How can physical activity preserve cognitive health and reduce the risk of dementia?Sedentary life, associated with poor lifestyle quality, is the usual culprit. Regular exercise canprevent, and even treat, dementia risk factors, such as hypertension (Valenzuela et al., 2021)and diabetes (via improving insulin resistance) (Kumar et al., 2019). Physical activity alsoimproves mental (depression, anxiety, stress, sleep quantity and quality) and psychosocialhealth (social isolation and loneliness), known risk factors for dementia (Nasisi, 2020).In addition to lowering the dementia risk factors, physical activity also impacts onbrain neuroplasticity, neurogenesis and angiogenesis. Namely physical activity, via reducingvascular risk factors and promoting cerebral perfusion, decreases white matter damage,which is associated with (post-stroke) cognitive decline and mortality (Hung et al., 2022).At a molecular level, exercise promotes brain derived neurotrophic factor (BDNF)release, especially in the anterior hippocampus (Sleiman et al., 2016), the region responsiblefor long-term encoding and retrieval of memory. The BDNF, on the other hand stimulatessynaptogenesis and neurogenesis. Regular exercise also increases the growth of new bloodvessels (angiogenesis) in the brain regions where neurogenesis occurs, providing theincreased blood supply that supports the development of these new neurons (Van der Borghtet al., 2009). In addition, neurotrophins, including BDNF and growth nerve factor, enhancethe release of acetylcholine (ACh) from hippocampal neurons, and this may influenceFrontiers in AgingNeuroscience 01 frontiersin.orgMukaetova-Ladinska et al. 10.3389/fnagi.2023.1140767the brain synaptic plasticity and synaptogenesis (Van der Borghtet al., 2009; Voss et al., 2019) while strengthening cognition. Thesechanges appear to be accompanied by improved memory andcerebrovascular regulation (Guadagni et al., 2020), in associationwith an increase of BDNF in the bloodstream (Binder andScharfman, 2004), ensuring that brain tissue consistently receivesadequate blood supply to meet its needs and preserve its function.Furthermore, moderate physical activity, i.e., treadmill exercise,reduces neuroinflammation and glial cell activation, decreasesamyloid β oligomers levels and improves synaptic transmissionin the prefrontal cortex in transgenic (3×) mouse models ofAlzheimer’s disease, possibly related to the inhibition of GSK3βkinase activity (Mu et al., 2022). This provides direct evidenceof physical activity modulating the extent of known Alzheimer’sdisease hallmarks, amyloid and neurofibrillary pathology, as wellas synaptic loss.The studies included in this special edition confirm the benefitsof physical exercise and extend them to promoting integrity andvolume of the brain white matter. Thus, irrespectively of whetherthese studies were performed in animal models (Chen L. et al.),younger (Song et al.) or older (Wolf et al.; Franchetti et al.) people,physical exercise led to additional improvement of cognition andwellbeing (Song et al.; Wolf et al.), alongside with increase oftotal brain volume (by 6% in “super aging” older adults; Kimet al.). However, the white matter integrity in distinct brain regionsappears to be dependent on the extent of physical activity. Thus,higher levels of physical activity enhance white matter integrity inbrain areas that have an impact on superior memory functioning,such as corpus callosum (Kim et al.), whereas Tai Chi and walkinghave an impact on higher fractional anisotropy values in the rightuncinate fasciculus and the left external capsule, but not corpuscallosum, in comparison to the sedentary adults (Chen F.-T. et al.).It is the stimulation of higher release of glutamate and acetylcholinethat underlies these psychological and cognitive improvementsseen during physical activity (Harasym et al.).These studies provide further support for the neuroprotectiverole of physical exercise. Thus, running, in particular, increasescerebral blood flow, reduces inflammation and enhances theexpression of neurotrophic factors, i.e., BDNF and insulin-likegrowth factor 1 (IGF-1) (Intlekofer et al., 2013), both known topromote the development and maintenance of neural circuits.The neurotrophins similarly interact with steroid hormones, i.e.,estrogen, and their interaction may underlie numerous neuronalevents, such as cell survival, synaptic plasticity and dendriticarborisation. The above findings are of clinical relevance since twothirds of women in menopause complain of cognitive problems,including difficulties in concentration, memory, planning and“brain fog”, with an earlier age at menopause resulting not onlyin a higher frequency of complaints (Hogervorst et al., 2022) butalso a higher risk of developing dementia (Rahman et al., 2020).Importantly, regular exercise is associated with improved whitematter microstructural integrity, regardless of the exercise type,evidence that could guide the development and application offuture prevention and intervention strategies designed to addressage-related cognitive impairments during late midlife (Chen F.-T.et al.). In addition, it is older adults in the 8th and 9th decadesthat may have greater benefits from engaging in physical activity(Franchetti et al.), a finding that may be attributable to reducingthe risk for cerebrovascular disease associated with white matterlesion load.Fractional anisotropy, an indicator of white matter integritytends to decrease with aging and even more with dementia.However, gaining new knowledge and skills (i.e., playing aninstrument, learning a new language etc.) result in increase in whitematter fibers that seems to be proportional to the number of hoursspent on these activities (Andrews et al., 2021). More importantly,white matter functioning improves within a few (2–4) weeks, asshown in the case of practicing meditation (Posner, 2020). Thesefindings have a meaningful and important role in tackling the whitematter lesions associated with several modifiable dementia riskfactors (i.e., diabetes, hypertension, smoking, hearing loss, obesity,depression, sedentary lifestyle, social isolation, sleep disturbances).Preliminary evidence from cross-sectional studies of treated riskfactors suggests that modification of these factors could slow downnegative effects on white matter microstructure.Themodifiable effects of physical activity are not only restrictedto physiological aging, but also continue in people with dementia,as it is shown recently in people with Alzheimer’s disease, viaregulating some of the disease biomarkers. That is, amyloid andtotal and phosphorylated (p181) tau protein in plasma (Yu et al.,2022). The findings of the studies in this collection collectivelysuggest that regular exercise is associated with improved whitematter microstructural integrity, regardless of the exercise type,age, gender. This could guide the development and applicationof future prevention and intervention strategies designed toaddress age-related cognitive impairments during late midlife(Chen F.-T. et al.). Forthcoming longitudinal and randomizedcontrol trials conducted on a larger sample of both young and oldercognitively intact and people with dementia are eagerly awaited toenhance prevention and therapeutic strategies to combat humanphysiological and pathological cognitive aging.Author contributionsAll authors have contributed in conceptualization of the paper,writing, and editing. All authors have approved the final version ofthe text for submission.Conflict of interestThe authors declare that the research was conducted in theabsence of any commercial or financial relationships that could beconstrued as a potential conflict of interest.Publisher’s noteAll claims expressed in this article are solely those of theauthors and do not necessarily represent those of their affiliatedorganizations, or those of the publisher, the editors and thereviewers. Any product that may be evaluated in this article, orclaim that may be made by its manufacturer, is not guaranteed orendorsed by the publisher.Frontiers in AgingNeuroscience 02 frontiersin.orgMukaetova-Ladinska et al. 10.3389/fnagi.2023.1140767ReferencesAndrews, E., Eierud, C., Banks, D., Harshbarger, T., Michael, A., and Rammell, C.(2021).Effects of lifelong musicianship on white matter integrity and cognitive brainreserve. Brain Sci. 11, 67. doi: 10.3390/brainsci11010067Binder, D. K., and Scharfman, H. E. (2004). 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Editorial: The impact of physical activity on white matter during healthy aging

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