Telomere shortening and decline in replicative potential as a function of donor age in human adrenocortical cells

Lianqing Yang, Tetsuya Suwa, Woodring E. Wright, Jerry W. Shay, Peter J. Hornsby

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Telomere shortening is the cause of replicative senescence of mammalian cells in culture and may be a cause of cellular aging in vivo. Some tissues clearly show telomere shortening during aging in humans, but the relationship between replication history and telomere length is obscured by complex relationships between stem cells and more differentiated cell types. Previous experiments on the adrenal cortex and human adrenocortical cells in culture indicate that the proliferative biology of this tissue is relatively simple; cell division occurs continuously throughout life, without evidence for a distinct stem cell compartment. In this tissue we investigated the relationship between telomere biology and replicative senescence by measuring replicative capacity and telomere length as a function of donor age. Cells cultured from adrenal tissue from donors of different ages showed a strong age-related decline in total replicative capacity, falling from about 50 population doublings for fetal cells to an almost total lack of division in culture for cells from older donors. Telomere restriction fragment (TRF) length was analyzed in the same sets of cells and decreased from a value of about 12 kb in fetal cells to approximately 7 kb in cells from older donors. The latter value is consistent with that in fibroblasts which have reached replicative senescence. Furthermore, there was a good correlation in individual donor samples between TRF length and replicative capacity in culture. To confirm the relationship between telomere length, telomerase, and replicative capacity, we measured telomere length in cells before and after infection with a retrovirus encoding hTERT, the catalytic component of human telomerase. The adult adrenal cortex does not have telomerase activity; cells after transduction with the hTERT retrovirus had high telomerase activity. Whereas control cells underwent a replication-dependent shortening in telomeres during long-term growth in culture, hTERT-modified cells maintained telomere length and are probably immortalized. Symmetric cell division in human adrenocortical cells, occurring slowly over the life span, is associated with progressive telomere shortening and may result in proliferative defects in vivo in old age, which could partly account for the age-related changes in the structure and function of the human adrenal cortex.

Original languageEnglish (US)
Pages (from-to)1685-1694
Number of pages10
JournalMechanisms of Ageing and Development
Volume122
Issue number15
DOIs
StatePublished - 2001

Fingerprint

Telomere Shortening
Telomerase
Telomere
Tissue
Cells
Stem cells
Cell Aging
Aging of materials
Adrenal Cortex
Fibroblasts
Cell culture
Cell Culture Techniques
Retroviridae
Cell Division
Stem Cells
Defects
Experiments
Cultured Cells
History
Tissue Donors

Keywords

  • Adrenal cortex
  • Immortalization
  • Replicative senescence
  • Telomeres

ASJC Scopus subject areas

  • Aging
  • Biochemistry
  • Developmental Biology
  • Developmental Neuroscience

Cite this

Telomere shortening and decline in replicative potential as a function of donor age in human adrenocortical cells. / Yang, Lianqing; Suwa, Tetsuya; Wright, Woodring E.; Shay, Jerry W.; Hornsby, Peter J.

In: Mechanisms of Ageing and Development, Vol. 122, No. 15, 2001, p. 1685-1694.

Research output: Contribution to journalArticle

@article{f733cb041e3c48428f321d63aebaa6fe,
title = "Telomere shortening and decline in replicative potential as a function of donor age in human adrenocortical cells",
abstract = "Telomere shortening is the cause of replicative senescence of mammalian cells in culture and may be a cause of cellular aging in vivo. Some tissues clearly show telomere shortening during aging in humans, but the relationship between replication history and telomere length is obscured by complex relationships between stem cells and more differentiated cell types. Previous experiments on the adrenal cortex and human adrenocortical cells in culture indicate that the proliferative biology of this tissue is relatively simple; cell division occurs continuously throughout life, without evidence for a distinct stem cell compartment. In this tissue we investigated the relationship between telomere biology and replicative senescence by measuring replicative capacity and telomere length as a function of donor age. Cells cultured from adrenal tissue from donors of different ages showed a strong age-related decline in total replicative capacity, falling from about 50 population doublings for fetal cells to an almost total lack of division in culture for cells from older donors. Telomere restriction fragment (TRF) length was analyzed in the same sets of cells and decreased from a value of about 12 kb in fetal cells to approximately 7 kb in cells from older donors. The latter value is consistent with that in fibroblasts which have reached replicative senescence. Furthermore, there was a good correlation in individual donor samples between TRF length and replicative capacity in culture. To confirm the relationship between telomere length, telomerase, and replicative capacity, we measured telomere length in cells before and after infection with a retrovirus encoding hTERT, the catalytic component of human telomerase. The adult adrenal cortex does not have telomerase activity; cells after transduction with the hTERT retrovirus had high telomerase activity. Whereas control cells underwent a replication-dependent shortening in telomeres during long-term growth in culture, hTERT-modified cells maintained telomere length and are probably immortalized. Symmetric cell division in human adrenocortical cells, occurring slowly over the life span, is associated with progressive telomere shortening and may result in proliferative defects in vivo in old age, which could partly account for the age-related changes in the structure and function of the human adrenal cortex.",
keywords = "Adrenal cortex, Immortalization, Replicative senescence, Telomeres",
author = "Lianqing Yang and Tetsuya Suwa and Wright, {Woodring E.} and Shay, {Jerry W.} and Hornsby, {Peter J.}",
year = "2001",
doi = "10.1016/S0047-6374(01)00280-9",
language = "English (US)",
volume = "122",
pages = "1685--1694",
journal = "Mechanisms of Ageing and Development",
issn = "0047-6374",
publisher = "Elsevier Ireland Ltd",
number = "15",

}

TY - JOUR

T1 - Telomere shortening and decline in replicative potential as a function of donor age in human adrenocortical cells

AU - Yang, Lianqing

AU - Suwa, Tetsuya

AU - Wright, Woodring E.

AU - Shay, Jerry W.

AU - Hornsby, Peter J.

PY - 2001

Y1 - 2001

N2 - Telomere shortening is the cause of replicative senescence of mammalian cells in culture and may be a cause of cellular aging in vivo. Some tissues clearly show telomere shortening during aging in humans, but the relationship between replication history and telomere length is obscured by complex relationships between stem cells and more differentiated cell types. Previous experiments on the adrenal cortex and human adrenocortical cells in culture indicate that the proliferative biology of this tissue is relatively simple; cell division occurs continuously throughout life, without evidence for a distinct stem cell compartment. In this tissue we investigated the relationship between telomere biology and replicative senescence by measuring replicative capacity and telomere length as a function of donor age. Cells cultured from adrenal tissue from donors of different ages showed a strong age-related decline in total replicative capacity, falling from about 50 population doublings for fetal cells to an almost total lack of division in culture for cells from older donors. Telomere restriction fragment (TRF) length was analyzed in the same sets of cells and decreased from a value of about 12 kb in fetal cells to approximately 7 kb in cells from older donors. The latter value is consistent with that in fibroblasts which have reached replicative senescence. Furthermore, there was a good correlation in individual donor samples between TRF length and replicative capacity in culture. To confirm the relationship between telomere length, telomerase, and replicative capacity, we measured telomere length in cells before and after infection with a retrovirus encoding hTERT, the catalytic component of human telomerase. The adult adrenal cortex does not have telomerase activity; cells after transduction with the hTERT retrovirus had high telomerase activity. Whereas control cells underwent a replication-dependent shortening in telomeres during long-term growth in culture, hTERT-modified cells maintained telomere length and are probably immortalized. Symmetric cell division in human adrenocortical cells, occurring slowly over the life span, is associated with progressive telomere shortening and may result in proliferative defects in vivo in old age, which could partly account for the age-related changes in the structure and function of the human adrenal cortex.

AB - Telomere shortening is the cause of replicative senescence of mammalian cells in culture and may be a cause of cellular aging in vivo. Some tissues clearly show telomere shortening during aging in humans, but the relationship between replication history and telomere length is obscured by complex relationships between stem cells and more differentiated cell types. Previous experiments on the adrenal cortex and human adrenocortical cells in culture indicate that the proliferative biology of this tissue is relatively simple; cell division occurs continuously throughout life, without evidence for a distinct stem cell compartment. In this tissue we investigated the relationship between telomere biology and replicative senescence by measuring replicative capacity and telomere length as a function of donor age. Cells cultured from adrenal tissue from donors of different ages showed a strong age-related decline in total replicative capacity, falling from about 50 population doublings for fetal cells to an almost total lack of division in culture for cells from older donors. Telomere restriction fragment (TRF) length was analyzed in the same sets of cells and decreased from a value of about 12 kb in fetal cells to approximately 7 kb in cells from older donors. The latter value is consistent with that in fibroblasts which have reached replicative senescence. Furthermore, there was a good correlation in individual donor samples between TRF length and replicative capacity in culture. To confirm the relationship between telomere length, telomerase, and replicative capacity, we measured telomere length in cells before and after infection with a retrovirus encoding hTERT, the catalytic component of human telomerase. The adult adrenal cortex does not have telomerase activity; cells after transduction with the hTERT retrovirus had high telomerase activity. Whereas control cells underwent a replication-dependent shortening in telomeres during long-term growth in culture, hTERT-modified cells maintained telomere length and are probably immortalized. Symmetric cell division in human adrenocortical cells, occurring slowly over the life span, is associated with progressive telomere shortening and may result in proliferative defects in vivo in old age, which could partly account for the age-related changes in the structure and function of the human adrenal cortex.

KW - Adrenal cortex

KW - Immortalization

KW - Replicative senescence

KW - Telomeres

UR - http://www.scopus.com/inward/record.url?scp=0034846018&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034846018&partnerID=8YFLogxK

U2 - 10.1016/S0047-6374(01)00280-9

DO - 10.1016/S0047-6374(01)00280-9

M3 - Article

VL - 122

SP - 1685

EP - 1694

JO - Mechanisms of Ageing and Development

JF - Mechanisms of Ageing and Development

SN - 0047-6374

IS - 15

ER -