Progeria syndromes and ageing: what is the connection?
Abstract
One of the many debated topics in ageing research is whether progeroid syndromes are really accelerated forms of human ageing. The answer requires a better understanding of the normal ageing process and the molecular pathology underlying these rare diseases. Exciting recent findings regarding a severe human progeria, Hutchinson-Gilford progeria syndrome, have implicated molecular changes that are also linked to normal ageing, such as genome instability, telomere attrition, premature senescence and defective stem cell homeostasis in disease development. These observations, coupled with genetic studies of longevity, lead to a hypothesis whereby progeria syndromes accelerate a subset of the pathological changes that together drive the normal ageing process.
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HGPS fibroblasts present biomarkers of aging and senescence.
“To determine if sEV-Ys within the CM had the potential to ameliorate biomarkers of aging, we took advantage of primary fibroblasts derived from patients with a severe form of premature aging, HGPS, which present biomarkers of aging and senescence (Figure S2A) (Burtner and Kennedy, 2010, Ocampo et al., 2016, Liu et al., 2011).”
From Small Extracellular Vesicles Have GST Activity and Ameliorate Senescence-Related Tissue Damage (2020) · cites this paper as Burtner and Kennedy, 2010
The segmental nature of each progeroid disease may be partially explained by differences in the specific DNA damage repair strategies used by each tissue and cell type.
“The segmental nature of each disease may be partially explained by differences in the specific DNA damage repair strategies used by each tissue and cell type186.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [186]
Most progeroid syndromes are associated with an increased burden of DNA damage that may directly affect the tissue stem cell compartment.
“studies indicate that, like chronologic aging, most progeroid syndromes are associated with an increased burden of DNA damage that may directly affect the tissue stem cell compartment186.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [186]
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- Authors
- Burtner, C. R., & Kennedy, B. K.
- Affiliations
- University of Washington (US)
- Buck Institute for Research on Aging (US)
- Corresponding author
- Kennedy, Brian K.
- ORCID
- Kennedy, Brian K.
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2010-08
- Volume
- 11
- Issue
- 8
- Pages
- 567-578
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- OpenAlex
- W2066442023
- Cited by
- 386
- References
- 165
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 12 · 2023: 14 · 2022: 20 · 2021: 23 · 2020: 19 · 2019: 27 · 2018: 25 · 2017: 29 · 2016: 34 · 2015: 36 · 2014: 28 · 2013: 27 · 2012: 31
- FWCI
- 2.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Institute on Aging (T32 AG-00057, T32AG000057)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- accelerated aging, Hutchinson-Gilford progeria syndrome, genomic instability, telomere shortening, premature senescence, stem cell homeostasis
- MeSH terms
- Aging, Animals, DNA Damage, DNA Repair, Biological Evolution, Humans, Longevity, Models, Biological, Progeria, Syndrome, Signal Transduction, Sirolimus, Lamin Type A, Mesenchymal Stem Cells
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