Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells

Karin Stenderup Dokkedahl, Jeannette Justesen, Christian Clausen, Moustapha Kassem

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Age-related decrease in bone formation is well described. However, the cellular causes are not known. Thus, we have established cultures of bone marrow stromal cells (MSC) from young (aged 18-29 years, n = 6) and old (aged 68-81 years, n = 5) donors. MSC were serially passaged until reaching maximal life span. Cell growth, markers of cellular senescence, and osteogenic and adipogenic potential were determined in early-passage and late-passage cells established from young and old donors. MSC from old donors exhibited a decreased maximal life span compared with cells from young donors (24 +/- 11 population doublings [PD] vs 41 +/- 10 PD, P <0.05) and mean PD rate was lower in old donor cells (0.05 +/- 0.02 PD/day) compared with young donor cells (0.09 +/- 0.02 PD/day) (P <0.05). No differences were detected in number of senescence-associated beta-galactosidase positive (SA beta-gal+) cells and mean telomere length in early-passage cells obtained from young and old donors. However, MSC from old donors exhibited accelerated senescence evidenced by increased number of SA beta-gal+ cells per PD as compared with young (4% per PD vs 0.4% per PD, respectively). MSC from young and old donors were able to form similar amounts of mineralized matrix in vitro and of normal lamellar bone in vivo. In adipogenic medium similar numbers of adipocytes formed in cultures of young and old donors. In conclusion, aging is associated with decreased proliferative capacity of osteoprogenitor cells, suggesting that decreased osteoblastic cell number, and not function, leads to age-related decrease in bone formation.
Original languageEnglish
JournalBone
Volume33
Issue number6
Pages (from-to)919-26
Number of pages8
ISSN8756-3282
Publication statusPublished - 1. Dec 2003

Fingerprint

Mesenchymal Stromal Cells
Stromal Cells
Population
Osteogenesis
Cell Aging
Telomere
Adipocytes
Growth

Keywords

  • Adipocytes
  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging
  • Animals
  • Biological Markers
  • Bone Marrow Cells
  • Calcification, Physiologic
  • Cell Aging
  • Cell Differentiation
  • Cell Division
  • Cell Size
  • Cell Transplantation
  • Cells, Cultured
  • Female
  • Humans
  • Injections, Subcutaneous
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Osteoblasts
  • Osteogenesis
  • Stromal Cells
  • Subcutaneous Tissue
  • Telomerase
  • Telomere
  • Transplantation, Heterologous
  • beta-Galactosidase

Cite this

Dokkedahl, Karin Stenderup ; Justesen, Jeannette ; Clausen, Christian ; Kassem, Moustapha. / Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. In: Bone. 2003 ; Vol. 33, No. 6. pp. 919-26.
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Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. / Dokkedahl, Karin Stenderup; Justesen, Jeannette; Clausen, Christian; Kassem, Moustapha.

In: Bone, Vol. 33, No. 6, 01.12.2003, p. 919-26.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells

AU - Dokkedahl, Karin Stenderup

AU - Justesen, Jeannette

AU - Clausen, Christian

AU - Kassem, Moustapha

PY - 2003/12/1

Y1 - 2003/12/1

N2 - Age-related decrease in bone formation is well described. However, the cellular causes are not known. Thus, we have established cultures of bone marrow stromal cells (MSC) from young (aged 18-29 years, n = 6) and old (aged 68-81 years, n = 5) donors. MSC were serially passaged until reaching maximal life span. Cell growth, markers of cellular senescence, and osteogenic and adipogenic potential were determined in early-passage and late-passage cells established from young and old donors. MSC from old donors exhibited a decreased maximal life span compared with cells from young donors (24 +/- 11 population doublings [PD] vs 41 +/- 10 PD, P <0.05) and mean PD rate was lower in old donor cells (0.05 +/- 0.02 PD/day) compared with young donor cells (0.09 +/- 0.02 PD/day) (P <0.05). No differences were detected in number of senescence-associated beta-galactosidase positive (SA beta-gal+) cells and mean telomere length in early-passage cells obtained from young and old donors. However, MSC from old donors exhibited accelerated senescence evidenced by increased number of SA beta-gal+ cells per PD as compared with young (4% per PD vs 0.4% per PD, respectively). MSC from young and old donors were able to form similar amounts of mineralized matrix in vitro and of normal lamellar bone in vivo. In adipogenic medium similar numbers of adipocytes formed in cultures of young and old donors. In conclusion, aging is associated with decreased proliferative capacity of osteoprogenitor cells, suggesting that decreased osteoblastic cell number, and not function, leads to age-related decrease in bone formation.

AB - Age-related decrease in bone formation is well described. However, the cellular causes are not known. Thus, we have established cultures of bone marrow stromal cells (MSC) from young (aged 18-29 years, n = 6) and old (aged 68-81 years, n = 5) donors. MSC were serially passaged until reaching maximal life span. Cell growth, markers of cellular senescence, and osteogenic and adipogenic potential were determined in early-passage and late-passage cells established from young and old donors. MSC from old donors exhibited a decreased maximal life span compared with cells from young donors (24 +/- 11 population doublings [PD] vs 41 +/- 10 PD, P <0.05) and mean PD rate was lower in old donor cells (0.05 +/- 0.02 PD/day) compared with young donor cells (0.09 +/- 0.02 PD/day) (P <0.05). No differences were detected in number of senescence-associated beta-galactosidase positive (SA beta-gal+) cells and mean telomere length in early-passage cells obtained from young and old donors. However, MSC from old donors exhibited accelerated senescence evidenced by increased number of SA beta-gal+ cells per PD as compared with young (4% per PD vs 0.4% per PD, respectively). MSC from young and old donors were able to form similar amounts of mineralized matrix in vitro and of normal lamellar bone in vivo. In adipogenic medium similar numbers of adipocytes formed in cultures of young and old donors. In conclusion, aging is associated with decreased proliferative capacity of osteoprogenitor cells, suggesting that decreased osteoblastic cell number, and not function, leads to age-related decrease in bone formation.

KW - Adipocytes

KW - Adolescent

KW - Adult

KW - Age Factors

KW - Aged

KW - Aged, 80 and over

KW - Aging

KW - Animals

KW - Biological Markers

KW - Bone Marrow Cells

KW - Calcification, Physiologic

KW - Cell Aging

KW - Cell Differentiation

KW - Cell Division

KW - Cell Size

KW - Cell Transplantation

KW - Cells, Cultured

KW - Female

KW - Humans

KW - Injections, Subcutaneous

KW - Male

KW - Mice

KW - Mice, Inbred NOD

KW - Mice, SCID

KW - Osteoblasts

KW - Osteogenesis

KW - Stromal Cells

KW - Subcutaneous Tissue

KW - Telomerase

KW - Telomere

KW - Transplantation, Heterologous

KW - beta-Galactosidase

M3 - Journal article

VL - 33

SP - 919

EP - 926

JO - Bone

JF - Bone

SN - 8756-3282

IS - 6

ER -