{"entity": "researcher", "timestamp": "2026-08-20T20:57:15.088Z", "family": "Forsberg", "given": "Lars A", "initials": "LA", "orcid": "0000-0002-1701-755X", "affiliations": ["Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden. lars.forsberg@igp.uu.se.", "The Beijer Laboratory, Uppsala University, Uppsala, Sweden. lars.forsberg@igp.uu.se."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/8954f351ff414d1899bc0715d74ff86d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/8954f351ff414d1899bc0715d74ff86d"}}, "publications": [{"entity": "publication", "iuid": "990ab699db164ff0b48897549ff7bdb3", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/990ab699db164ff0b48897549ff7bdb3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/990ab699db164ff0b48897549ff7bdb3"}}, "title": "Hematopoietic loss of Y chromosome activates immune checkpoints and contributes to impaired senescent cell clearance and renal disease.", "authors": [{"family": "Arai", "given": "Yohei", "initials": "Y", "orcid": "0009-0002-7458-0266", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b547447efdbe4892b104d83e478cf73c.json"}}, {"family": "Chavkin", "given": "Nicholas W", "initials": "NW", "orcid": "0000-0001-9058-0245", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d743aefa38fa4698a3c8a2df945e85ae.json"}}, {"family": "Arai", "given": "Yuka", "initials": "Y"}, {"family": "Halvardson", "given": "Jonatan", "initials": "J", "orcid": "0000-0002-5533-1953", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fd5990b9edc749c9baa53290222e9255.json"}}, {"family": "Bjurling", "given": "Josefin", "initials": "J", "orcid": "0009-0006-7675-429X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/814171cd17eb40359b99086e4589d2a9.json"}}, {"family": "Doviak", "given": "Heather", "initials": "H", "orcid": "0000-0002-0720-3164", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8d970fc52e09468fb7bcba8a089814ab.json"}}, {"family": "Cochran", "given": "Jesse D", "initials": "JD", "orcid": "0000-0001-9705-5785", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e5b75b49335a44298e9e1b6e76d94b53.json"}}, {"family": "Evans", "given": "Megan A", "initials": "MA"}, {"family": "Horitani", "given": "Keita", "initials": "K", "orcid": "0009-0000-0909-9658", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/67ec8db5646644eb8c3f5d2a65054e64.json"}}, {"family": "Yura", "given": "Yoshimitsu", "initials": "Y", "orcid": "0000-0003-2618-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/154bd289c3f84d9c841212642cb4b044.json"}}, {"family": "Miura-Yura", "given": "Emiri", "initials": "E", "orcid": "0000-0002-5477-5886", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fa27affe09e14c889e91a8f3c2f72593.json"}}, {"family": "Sano", "given": "Soichi", "initials": "S", "orcid": "0000-0002-3361-0839", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9862fb8d024948fdbd707bb9fb03161b.json"}}, {"family": "Forsberg", "given": "Lars A", "initials": "LA", "orcid": "0000-0002-1701-755X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8954f351ff414d1899bc0715d74ff86d.json"}}, {"family": "Walsh", "given": "Kenneth", "initials": "K", "orcid": "0000-0001-7580-2276", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d3d341f0f05e499f98ca01d583703783.json"}}], "type": "journal article", "published": "2025-08-06", "journal": {"title": "Sci Transl Med", "issn": "1946-6242", "volume": "17", "issue": "810", "pages": "eadv4071", "issn-l": "1946-6234"}, "abstract": "The accumulation of senescent cells contributes to morbidity and mortality; however, common mechanisms underpinning this age-associated phenomenon remain elusive. Hematopoietic loss of the Y chromosome (LOY) is the most frequently acquired somatic mutation in males, and this condition has been associated with various age-associated diseases and reduced lifespan. Therefore, we investigated the role of hematopoietic LOY in promoting cellular senescence, focusing on kidney disease because of its well-documented connection with aging and senescence. Herein, a prospective cohort study revealed that LOY in blood is associated with an increased incidence of kidney diseases. Analyses of transcriptional signatures in human kidneys found that immune cell LOY is enriched in patients with kidney disease and associated with greater amounts of cellular senescence. In male mice reconstituted with bone marrow lacking the Y chromosome, renal dysfunction was accompanied by senescent cell accumulation in models of kidney injury and advanced age. Treatment with a senolytic agent promoted senolysis and preferentially inhibited the progression of renal dysfunction in LOY mice. Hematopoietic LOY led to up-regulation of multiple immune inhibitory receptors, and treatment with the combination of antibodies targeting PD-1 (programmed cell death protein 1) and SIRP\u03b1 (signal regulatory protein \u03b1) reduced senescent cell accumulation and rescued the renal pathology conferred by hematopoietic LOY in the kidney injury model. Collectively, these data indicate that hematopoietic LOY contributes to pathological conditions by impairing the clearance of senescent cells through up-regulation of immune checkpoint proteins.", "doi": "10.1126/scitranslmed.adv4071", "pmid": "40768598", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS2107368"}, {"db": "pmc", "key": "PMC12683723"}, {"db": "GEO", "key": "GSE301560"}], "notes": [], "created": "2026-08-20T11:59:58.272Z", "modified": "2026-08-20T11:59:58.583Z"}, {"entity": "publication", "iuid": "a386bee03a3a431eada00c785785e925", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a386bee03a3a431eada00c785785e925.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a386bee03a3a431eada00c785785e925"}}, "title": "Hematopoietic loss of Y chromosome leads to cardiac fibrosis and heart failure mortality.", "authors": [{"family": "Sano", "given": "Soichi", "initials": "S", "orcid": "0000-0002-3361-0839", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9862fb8d024948fdbd707bb9fb03161b.json"}}, {"family": "Horitani", "given": "Keita", "initials": "K"}, {"family": "Ogawa", "given": "Hayato", "initials": "H", "orcid": "0000-0002-1313-4230", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4ea30d3ba2d4e28b033737208005501.json"}}, {"family": "Halvardson", "given": "Jonatan", "initials": "J", "orcid": "0000-0002-5533-1953", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fd5990b9edc749c9baa53290222e9255.json"}}, {"family": "Chavkin", "given": "Nicholas W", "initials": "NW", "orcid": "0000-0001-9058-0245", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d743aefa38fa4698a3c8a2df945e85ae.json"}}, {"family": "Wang", "given": "Ying", "initials": "Y", "orcid": "0000-0002-6249-1859", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7956bc76076d48d7ab8e109a0a628997.json"}}, {"family": "Sano", "given": "Miho", "initials": "M"}, {"family": "Mattisson", "given": "Jonas", "initials": "J", "orcid": "0000-0002-4456-9667", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/55ab3f88462844d9884e8787bd46236a.json"}}, {"family": "Hata", "given": "Atsushi", "initials": "A", "orcid": "0000-0002-9578-683X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/54d30610e72b4509919ce747a42d639a.json"}}, {"family": "Danielsson", "given": "Marcus", "initials": "M", "orcid": "0000-0003-4418-0165", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d41181bacaa34f13ad8e4455e36566d4.json"}}, {"family": "Miura-Yura", "given": "Emiri", "initials": "E", "orcid": "0000-0002-5477-5886", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fa27affe09e14c889e91a8f3c2f72593.json"}}, {"family": "Zaghlool", "given": "Ammar", "initials": "A"}, {"family": "Evans", "given": "Megan A", "initials": "MA"}, {"family": "Fall", "given": "Tove", "initials": "T", "orcid": "0000-0003-2071-5866", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7dbbd468e6da4727b69333ade942c071.json"}}, {"family": "De Hoyos", "given": "Henry N", "initials": "HN", "orcid": "0000-0002-2083-1261", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9ec61e9e0f2b4d40ba33538dbb560702.json"}}, {"family": "Sundstr\u00f6m", "given": "Johan", "initials": "J", "orcid": "0000-0003-2247-8454", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2e1b8ae02d2949acaa8c2e18349b33a1.json"}}, {"family": "Yura", "given": "Yoshimitsu", "initials": "Y", "orcid": "0000-0003-2618-8569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/154bd289c3f84d9c841212642cb4b044.json"}}, {"family": "Kour", "given": "Anupreet", "initials": "A"}, {"family": "Arai", "given": "Yohei", "initials": "Y"}, {"family": "Thel", "given": "Mark C", "initials": "MC"}, {"family": "Arai", "given": "Yuka", "initials": "Y"}, {"family": "Mychaleckyj", "given": "Josyf C", "initials": "JC", "orcid": "0000-0003-2595-0005", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/eb04d147da184365831b33aedfef9cad.json"}}, {"family": "Hirschi", "given": "Karen K", "initials": "KK", "orcid": "0000-0001-7116-0130", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d70c2feaf8b74f75b80a0fb9dbb5f040.json"}}, {"family": "Forsberg", "given": "Lars A", "initials": "LA", "orcid": "0000-0002-1701-755X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8954f351ff414d1899bc0715d74ff86d.json"}}, {"family": "Walsh", "given": "Kenneth", "initials": "K", "orcid": "0000-0001-7580-2276", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d3d341f0f05e499f98ca01d583703783.json"}}], "type": "journal article", "published": "2022-07-15", "journal": {"title": "Science (New York, N.Y.)", "issn": "1095-9203", "volume": "377", "issue": "6603", "pages": "292-297", "issn-l": "0036-8075"}, "abstract": "Hematopoietic mosaic loss of Y chromosome (mLOY) is associated with increased risk of mortality and age-related diseases in men, but the causal and mechanistic relationships have yet to be established. Here, we show that male mice reconstituted with bone marrow cells lacking the Y chromosome display increased mortality and age-related profibrotic pathologies including reduced cardiac function. Cardiac macrophages lacking the Y chromosome exhibited polarization toward a more fibrotic phenotype, and treatment with a transforming growth factor \u03b21-neutralizing antibody ameliorated cardiac dysfunction in mLOY mice. A prospective study revealed that mLOY in blood is associated with an increased risk for cardiovascular disease and heart failure-associated mortality. Together, these results indicate that hematopoietic mLOY causally contributes to fibrosis, cardiac dysfunction, and mortality in men.", "doi": "10.1126/science.abn3100", "pmid": "35857592", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1830716"}, {"db": "pmc", "key": "PMC9437978"}], "notes": [], "created": "2026-08-20T11:59:34.066Z", "modified": "2026-08-20T11:59:34.628Z"}, {"entity": "publication", "iuid": "dd67852f6b454c12a3863fa03d159efa", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/dd67852f6b454c12a3863fa03d159efa.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/dd67852f6b454c12a3863fa03d159efa"}}, "title": "Reply to Guo's commentary on: \"Immune cells lacking Y chromosome show dysregulation of autosomal gene expression\".", "authors": [{"family": "Forsberg", "given": "Lars A", "initials": "LA", "orcid": "0000-0002-1701-755X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8954f351ff414d1899bc0715d74ff86d.json"}}], "type": "letter", "published": "2021-12-15", "journal": {"title": "Cell. Mol. Life Sci.", "issn": "1420-9071", "volume": "79", "issue": "1", "pages": "30", "issn-l": "1420-682X"}, "abstract": null, "doi": "10.1007/s00018-021-04028-w", "pmid": "34910245", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8732829"}, {"db": "pii", "key": "10.1007/s00018-021-04028-w"}], "notes": [], "created": "2026-08-20T06:38:36.237Z", "modified": "2026-08-20T06:38:36.323Z"}, {"entity": "publication", "iuid": "a2fd1e66b6924d19a34d3b3e8eb5146f", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a2fd1e66b6924d19a34d3b3e8eb5146f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a2fd1e66b6924d19a34d3b3e8eb5146f"}}, "title": "Reply to Veitia.", "authors": [{"family": "Danielsson", "given": "Marcus", "initials": "M", "orcid": "0000-0003-4418-0165", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d41181bacaa34f13ad8e4455e36566d4.json"}}, {"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Mattisson", "given": "Jonas", "initials": "J", "orcid": "0000-0002-4456-9667", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/55ab3f88462844d9884e8787bd46236a.json"}}, {"family": "Forsberg", "given": "Lars A", "initials": "LA", "orcid": "0000-0002-1701-755X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8954f351ff414d1899bc0715d74ff86d.json"}}], "type": "letter", "published": "2021-09-00", "journal": {"title": "Eur. J. Hum. Genet.", "issn": "1476-5438", "volume": "29", "issue": "9", "pages": "1323-1324", "issn-l": "1018-4813"}, "abstract": null, "doi": "10.1038/s41431-020-00802-9", "pmid": "33462398", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8440652"}, {"db": "pii", "key": "10.1038/s41431-020-00802-9"}], "notes": [], "created": "2026-08-20T08:50:08.464Z", "modified": "2026-08-20T08:50:08.574Z"}, {"entity": "publication", "iuid": "4138f96fa9384659834dcd9e01e09412", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/4138f96fa9384659834dcd9e01e09412.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/4138f96fa9384659834dcd9e01e09412"}}, "title": "Intra-individual changes in the frequency of mosaic loss of chromosome Y over time estimated with a new method", "authors": [{"family": "Danielsson", "given": "Marcus", "initials": "M"}, {"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Davies", "given": "Hanna", "initials": "H"}, {"family": "Moghadam", "given": "Behrooz Torabi", "initials": "BT"}, {"family": "Mattisson", "given": "Jonas", "initials": "J"}, {"family": "Rychlicka-Buniowska", "given": "Edyta", "initials": "E"}, {"family": "Jaszczy\u0144ski", "given": "Janusz", "initials": "J"}, {"family": "Heintz", "given": "Julia", "initials": "J"}, {"family": "Lannfelt", "given": "Lars", "initials": "L"}, {"family": "Giedraitis", "given": "Vilmantas", "initials": "V"}, {"family": "Ingelsson", "given": "Martin", "initials": "M"}, {"family": "Dumanski", "given": "Jan P", "initials": "JP"}, {"family": "Forsberg", "given": "Lars A", "initials": "LA", "orcid": "0000-0002-1701-755X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8954f351ff414d1899bc0715d74ff86d.json"}}], "type": "posted-content", "published": "2019-05-09", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/631713", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:13:41.548Z", "modified": "2026-08-20T11:13:41.564Z"}, {"entity": "publication", "iuid": "f34bcac96b2b4842b0f4ef9106989a55", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f34bcac96b2b4842b0f4ef9106989a55.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f34bcac96b2b4842b0f4ef9106989a55"}}, "title": "Back to the drawing board-loss of chromosome Y (LOY) in leukocytes is associated with age-related macular degeneration.", "authors": [{"family": "Forsberg", "given": "Lars A", "initials": "LA", "orcid": "0000-0002-1701-755X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8954f351ff414d1899bc0715d74ff86d.json"}}], "type": "journal article", "published": "2019-01-00", "journal": {"title": "Eur. J. Hum. Genet.", "issn": "1476-5438", "volume": "27", "issue": "1", "pages": "17-19", "issn-l": "1018-4813"}, "abstract": null, "doi": "10.1038/s41431-018-0261-9", "pmid": "30353152", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6303245"}, {"db": "pii", "key": "10.1038/s41431-018-0261-9"}], "notes": [], "created": "2026-08-20T08:50:06.482Z", "modified": "2026-08-20T08:50:06.555Z"}]}