{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T17:05:06Z","timestamp":1772471106377,"version":"3.50.1"},"reference-count":134,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Public Health"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      During the COVID-19 pandemic, prolonged mask use exposed billions of people to repeatedly elevated inhaled CO\n                      <jats:sub>2<\/jats:sub>\n                      levels for extended periods. While these exposures typically produce only small pH shifts in healthy adults, older individuals exhibit age-related declines in respiratory, renal, metabolic, and proteostatic resilience that reduce their ability to buffer such disturbances. Because even mild acidosis can influence protein folding and accelerate amyloid formation under conditions of impaired homeostasis, aging populations may be disproportionately susceptible to downstream effects of chronic low-grade CO\n                      <jats:sub>2<\/jats:sub>\n                      exposure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This narrative review synthesizes data on age-related changes in ventilation, acid\u2013base regulation, metabolic buffering, and proteostasis, integrating these with biochemical pathways of pH-dependent amyloidogenesis. Evidence from mask-related CO\n                      <jats:sub>2<\/jats:sub>\n                      exposure studies, protein-misfolding research, and gerontological physiology was analyzed to evaluate whether age-specific vulnerability could plausibly modulate amyloidogenic risk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Across multiple studies, mask wearing increases inhaled CO\n                      <jats:sub>2<\/jats:sub>\n                      concentrations and produces small but measurable reductions in blood pH in some conditions. Although these changes remain within normal physiological range in healthy adults, aging is associated with impaired ventilatory responsiveness to hypercapnia, diminished renal compensation, reduced muscle-based buffering due to sarcopenia, and mitochondrial and proteostatic decline. These changes lower physiological reserve and may magnify the biological impact of minor pH fluctuations. Experimental literature consistently demonstrates that acidity accelerates amyloid formation in proteins relevant to aging disorders\u2014including A\u03b2, \u03b1-synuclein, IAPP, and \u03b2\n                      <jats:sub>2<\/jats:sub>\n                      -microglobulin\u2014while older adults also accumulate comorbidities (chronic kidney disease, diabetes, neurodegeneration) that themselves predispose to acidosis and amyloidogenic stress.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Although mask-associated CO\n                      <jats:sub>2<\/jats:sub>\n                      elevations appear insufficient to induce amyloid formation in isolation, the combination of age-related physiological decline, chronic inflammation, impaired proteostasis, and reduced buffering capacity may heighten vulnerability in older adults. Given global demographic aging, further age-stratified research is needed to clarify long-term implications of repeated low-grade hypercapnia, refine diagnostic approaches for early detection of proteostatic stress, and develop prevention strategies tailored to aging physiology.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpubh.2026.1759011","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T16:23:56Z","timestamp":1772468636000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Physiological responses to mask-associated CO2 exposure: a narrative review of acid\u2013base balance, aging, and amyloidogenic stress"],"prefix":"10.3389","volume":"14","author":[{"given":"Mawadda","family":"Alghrably","sequence":"first","affiliation":[{"name":"Smart-Health Initiative (SHI) and Red Sea Research Center (RSRC), Division of Biological and Environmental 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