{"id":5007,"date":"2021-07-21T15:30:20","date_gmt":"2021-07-21T06:30:20","guid":{"rendered":"https:\/\/www.emukk.com\/WP\/?p=5000"},"modified":"2021-07-21T22:29:41","modified_gmt":"2021-07-21T13:29:41","slug":"age-dependent-t-cell-telomere-length-shortening-affects-covid-19-severity","status":"publish","type":"post","link":"https:\/\/www.emukk.com\/WP\/en\/age-dependent-t-cell-telomere-length-shortening-affects-covid-19-severity\/","title":{"rendered":"Age-dependent T-cell telomere length shortening affects COVID-19 severity\u00a0"},"content":{"rendered":"

A group from University of Washington, Seattle, USA, etc. has reported that age-dependent T-cell telomere length shortening affects COVID-19 severity.
\nhttps:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8282112\/<\/a><\/p>\n

Transient lymphopenia is a common feature of acute viral respiratory infections. The drastic and prolonged lymphopenia of COVID-19, however, is distinctive and largely stems from falling counts of T cells. Although the primary causes of this T-cell lymphopenia is still poorly understood, the decline in T-cell count in COVID-19 demands fast and massive T-cell clonal expansion, which is a telomere length (TL)-dependent issue. As hematopoietic cell TL (HCTL) shortens with age, T-cells from some older adults might lack the clonal expansion capacity required to offset the development of COVID-19 lymphopenia or recover from it.<\/p>\n

In absence of an acute infection, the T cell turnover is slow because of the relatively long biological half-lives of na\u00efve T cells and memory T cells in the circulation, i.e., ~ 5 years and ~ 5 months, respectively. In the face of SARS-CoV-2 infection, however, diminished TL-dependent T-cell proliferative capacity in older adults could result in a shortfall between T-cell depletion and repletion. Moreover, the clearance of SARS-CoV-2 requires clonal expansion and differentiation of na\u00efve T cells into SARS-CoV-2 antigen-specific effector\/memory (henceforth memory) T cells . Short na\u00efve T-cell telomeres might thus limit adaptive immunity against the virus even without infection-mediated T-cell lymphopenia.<\/p>\n

The following assumptions on T-cell replication and T-cell clone size (CS) are used in the following author’s model:
\n(i) T-cell TL-dependent cessation of replication is defined by a \u201ctelomeric brink\u201d (TLB) that stops replication at 5 kilobases, (ii) TL of a na\u00efve T cell at age 20 years (TL20<\/sub>) progressively shortens at a rate g of 0.03 kb\/year until it reaches the TLB, (iii) In exponential growth, a single na\u00efve T cell can generate a maximal CS (MCS) of ~ 106 (one million) memory T cells through ~ 20 replications (Nmax), (iv) the maximal TL shortening due to clonal expansion is defined as \u0394max<\/sub>, (v) Due to age-dependent TL shortening, a na\u00efve T- cell TL reaches the \u201ctelomeric onset\u201d (TLO = 6.4 kb) at \u201cage of onset\u201d (XO<\/sub>), (vi) Most memory T cells are formed in response to new antigens during childhood and early adulthood.<\/p>\n

\"\"<\/a>
\nTL20<\/sub> = TL at age 20 years,
\nTLB<\/sub> = Telomeric brink, stopping cell replication,
\nTLO<\/sub> = TL at onset of clone size limitation,
\nXO<\/sub> = Age in years when TLO is reached,
\nMCS = Maximal clone size (~106 T cells),
\n\u0394max<\/sub> = TL shortening required for achieving MCS (~1.4kb)<\/p>\n

In conclusion, the TL effect on na\u00efve T-cell clonal expansion probably influences the outcome of SARS-CoV-2 infection, because it becomes difficult to supply enough amount of T cell clone size with aging (with shortening TL).<\/p>\n","protected":false},"excerpt":{"rendered":"

A group from University of Washington, Seattle, USA, etc. has reported that age-dependent T-cell telomere leng<\/p><\/div>\n

\u7d9a\u304d\u3092\u8aad\u3080<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[70],"tags":[],"class_list":["post-5007","post","type-post","status-publish","format-standard","hentry","category-nature-en"],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/www.emukk.com\/WP\/wp-json\/wp\/v2\/posts\/5007","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.emukk.com\/WP\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.emukk.com\/WP\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.emukk.com\/WP\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.emukk.com\/WP\/wp-json\/wp\/v2\/comments?post=5007"}],"version-history":[{"count":4,"href":"https:\/\/www.emukk.com\/WP\/wp-json\/wp\/v2\/posts\/5007\/revisions"}],"predecessor-version":[{"id":5039,"href":"https:\/\/www.emukk.com\/WP\/wp-json\/wp\/v2\/posts\/5007\/revisions\/5039"}],"wp:attachment":[{"href":"https:\/\/www.emukk.com\/WP\/wp-json\/wp\/v2\/media?parent=5007"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.emukk.com\/WP\/wp-json\/wp\/v2\/categories?post=5007"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.emukk.com\/WP\/wp-json\/wp\/v2\/tags?post=5007"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}