{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:08:31Z","timestamp":1787875711866,"version":"build-2784847793"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["430174701"],"award-info":[{"award-number":["430174701"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018694","name":"HORIZON EUROPE Marie Sklodowska-Curie Actions","doi-asserted-by":"publisher","award":["101069035"],"award-info":[{"award-number":["101069035"]}],"id":[{"id":"10.13039\/100018694","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["430170797"],"award-info":[{"award-number":["430170797"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005156","name":"Alexander von Humboldt-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005156","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007537","name":"Freie Universit\u00e4t Berlin","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007537","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,1,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Aging, the decline in physiological function over time, is marked by the intracellular accumulation of damaged components. It can be attributed to trade-offs between organismal maintenance and the generation of high-quality offspring, where the parent retains damage upon reproduction and produces rejuvenated descendants. This occurs even in bacteria, such as\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      , which asymmetrically partition aggregates of misfolded proteins upon division. However, there is conflicting evidence on the fitness impact of protein aggregates, ranging from detrimental effects to enhanced stress survival. Here, we show that the decisive factor driving growth decline in\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      is not the presence of an aggregate, but the fraction of the intracellular space it occupies. By following single-cell\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      lineages expressing fluorescently labeled DnaK chaperones, we quantified damage accumulation and partitioning across generations in microfluidic devices. We found that the diameter of aggregates increases at linear rates, and cell growth declines as a function of the intracellular space lost to damage. At the same time, however, the mother cell undergoes a progressive enlargement that accommodates the growing aggregate. This could be regarded as a compensatory mechanism, allowing the mother to sustain stable growth despite the continuous accumulation of damage and resulting in the emergence of a morphological asymmetry between mother and daughter cells, challenging the long-standing assumption that\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      divides symmetrically. Our findings point to a more complex role of protein aggregation, with implications for our understanding of the cellular mechanisms underlying aging, as well as its evolutionary origins.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Among the simplest organisms known to age,\n                        <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                        bacteria suffer a functional decline as misfolded proteins accumulate into aggregates retained by the mother cell upon division. This mechanism places the loss of proteostasis as a conserved hallmark of aging. However, subsequent studies found no deleterious effects of harboring aggregates. By quantifying single-cell fitness and damage dynamics, we found that it is not the mere presence of an aggregate that drives a fitness decline, but the intracellular space it occupies. Yet, aging cells undergo a gradual enlargement that could allow them to sustain stable growth despite harboring intracellular damage. Cell enlargement thus emerges as another cross-domain aging phenotype, but with curiously opposite effects: protective in bacteria, whereas generally deleterious in eukaryotes. Our findings, therefore, offer a connection between damage dynamics, aging, and cell size regulation at the single-cell level, while tracing new parallels between bacterial and eukaryotic aging.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.02050-25","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T14:01:47Z","timestamp":1765893707000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Protein aggregation drives cell aging in a size-specific manner in\n                    <i>Escherichia coli<\/i>"],"prefix":"10.1128","volume":"17","author":[{"given":"Linda","family":"Wagener","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/046ak2485","id-type":"ROR","asserted-by":"publisher"}],"name":"Freie Universit\u00e4t Berlin, Institute of Biology","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7173-0671","authenticated-orcid":false,"given":"Arpita","family":"Nath","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/046ak2485","id-type":"ROR","asserted-by":"publisher"}],"name":"Freie Universit\u00e4t Berlin, Institute of Biology","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8523-0758","authenticated-orcid":false,"given":"Murat","family":"Tu\u011frul","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/046ak2485","id-type":"ROR","asserted-by":"publisher"}],"name":"Freie Universit\u00e4t Berlin, Institute of Biology","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1897-2305","authenticated-orcid":true,"given":"Abram","family":"Aertsen","sequence":"additional","affiliation":[{"name":"Department of Microbial and Molecular Systems, KU Leuven","place":["Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1778-5989","authenticated-orcid":true,"given":"Ulrich K.","family":"Steiner","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/046ak2485","id-type":"ROR","asserted-by":"publisher"}],"name":"Freie Universit\u00e4t Berlin, Institute of Biology","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3747-9719","authenticated-orcid":true,"given":"Audrey M.","family":"Proenca","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/046ak2485","id-type":"ROR","asserted-by":"publisher"}],"name":"Freie Universit\u00e4t Berlin, Institute of Biology","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.05.039"},{"key":"e_1_3_4_3_2","volume-title":"Evolutionary biology of aging","author":"Rose MR","year":"1991","unstructured":"Rose MR. 1991. 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