AgingNCT00242255
Epigenetics in the Aging Process
An observational study of Aging, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 4 sites in United States.
Trial summary
This study will examine the role of epigenetics (heritable changes in gene function that occur without a change in DNA sequence) in the aging process. DNA is the primary genetic material, responsible for transmitting information from one cell to the next or from one generation to the next. Read more about this study
- Who is it for?
- Ages 14 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Aging
- How many people
- 90 participants
- Where
- 4 sitesUnited States
- Study dates
- 23 Sep 2008to 5 Feb 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 to 90 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Neonatal cord blood samples collected in association with normal deliveries at a NICHD obstetrics service in Wayne State University (PI Dr. Roberto Romero). Adult samples collected from volunteers at the NIH Blood Bank.
Who may be able to join
- Age 21-30 or 65-90, female or male
- Normal liver function, renal function adjusted for age
- Written informed consent
Who cannot join
- Down's or other premature aging syndromes
- Mastectomies: skin involvement in the malignant process or damage due to prior radiation therapy
- Active skin infection
- Skin damage due to photoaging will be noted but will not be a basis for exclusion
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Suburban Hospital
Bethesda, Maryland, 20814
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
Virginia Commonwealth University
Richmond, Virginia, 23284
GW University Medical Center
Washington D.C., District of Columbia, 20037
About this study
Official title: Remodeling of Chromatin-Based Epigenetic Structures in Development and Aging
This study will examine the role of epigenetics (heritable changes in gene function that occur without a change in DNA sequence) in the aging process. DNA is the primary genetic material, responsible for transmitting information from one cell to the next or from one generation to the next. A second layer of heredity is described by the term "epigenetics."
Epigenetic information is reset from one generation to the next. It works in two ways: 1) by modification of the DNA, like balloons stuck at irregular intervals onto the sides of the DNA helix that encodes genes, and 2) through specialized protein shells that wrap around some regions of DNA. As in DNA, these shells can copy themselves and can transmit instructions. Because they are used to turn genes on and off, errors in their settings cause critical misinformation to be transmitted.
Read more
Aging involves many changes, such as muscle weakening, graying hair, skin wrinkling, and so forth. There are several current theories of aging, including damage to genes by oxidation, shortening of tiny structures at the ends of chromosomes called telomeres, and the ability to stretch lifespan with caloric restrictions. This study will investigate the possible role of epigenetics in aging by examining and comparing the shell-like epigenetic settings in skin cells in young adults and older individuals. Preliminary results from earlier studies show differences in these settings in younger and older people.
Women between the ages of 21 and 30 years and 65 and 90 years who are undergoing breast reduction or mastectomy at Suburban Hospital in Bethesda, Maryland, may participate in this study. Tissue removed during surgery for pathological examination will also be used by researchers in this study to validate the preliminary findings noted above and to continue studies into the new area of epigenetics and aging.
...
Read the detailed description
Normal human lifespan is marked by a complex series of developmental events, relative stability during adulthood, and ultimately a gradual decline in viability. Biological clocks presumably underlie the developmental events that occur through childhood and adolescence, but the nature of those clocks has remained obscure. Progress in this area would be of considerable importance, not only for our understanding of child development, but also because instability in putative clock-like mechanisms may occur as part of the aging process. Such instability could well compromise tissue function and contribute to many of the common degenerative diseases of later life. We propose to investigate whether developmental clocks and related aspects of the aging process are attributable in part to age-related epigenome remodeling. Experiments done to date with cultured human fibroblasts derived from tissue banks provide tentative support for this hypothesis. To exclude tissue culture-related artifacts and to continue the work, it is essential to have access to fresh tissue material in the form of surgically obtained skin specimens that would otherwise be discarded. Elective breast reduction mammoplasty is a frequently performed surgery at Suburban Hospital, Bethesda, Maryland. Small skin specimens will be obtained from this procedure, as well as from normal skin derived from mastectomies. Patients who are to undergo these procedures will be asked to sign a consent form allowing the specimens, normally discarded, to be used instead for research on the mechanism of aging. They will be informed that clinical information will accompany the specimens, including age and known disease conditions. Twenty patients in each of two age ranges, 21-30 yr and 65-90 yr, will be enrolled in the study. The primary outcome will be confirmation of age-related epigenome change in the chromosome 4q35.2 region, previously documented using tissue bank-derived cultured skin fibroblasts. Mapping and sampling chromatin from this region revealed higher histone H4 acetylation in young (24-30 yr) than old (80-85 yr) individuals. Confirmation of this change in primary fibroblasts will be followed by more detailed mapping of chromatin structure and extension beyond the currently defined limits. Secondary outcomes will include examination of two areas of epigenome remodeling that appear to occur between birth and adulthood, as well as searches for additional regions of age-related chromatin change.
- Conditions
- Aging
- Keywords
- Histone, Chromatin, Epigenome, Senescence, Acetylation, Aging, Tissue Sample
What is being measured
The primary outcome is the main question the study is designed to answer.
Improved understanding of dynamic epigenome change and its roles in development and aging
Publication of scholarly articles describing previously unknown modes of postnatal human epigenome change and their consequences for gene expression.
Measured: Cross-sectional study design with measures corresponding to collection time point
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2005 (estimated)
- Study start23 Sep 2008
- Primary completion4 May 2020
- Study completion5 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for AgingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Bruce H Howard, M.D., Principal investigator, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00242255
- Sponsor's protocol ID
- 060010
- Other IDs
- 06-CH-0010
- Status last verified
- Feb 2021
- First submitted
- 19 Oct 2005
- Last updated
- 9 Feb 2021
- Results posted
- No
Publications
Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell. 2005 Feb 25;120(4):483-95. doi: 10.1016/j.cell.2005.02.001.
PubMed 15734681Bandyopadhyay D, Medrano EE. The emerging role of epigenetics in cellular and organismal aging. Exp Gerontol. 2003 Nov-Dec;38(11-12):1299-307. doi: 10.1016/j.exger.2003.09.009.
PubMed 14698809Bestor TH. The DNA methyltransferases of mammals. Hum Mol Genet. 2000 Oct;9(16):2395-402. doi: 10.1093/hmg/9.16.2395.
PubMed 11005794
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Remodeling of Chromatin-Based Epigenetic Structures in Development and Aging
- ClinicalTrials.gov ID
- NCT00242255
- Acronym / sponsor ID
- 060010
- Conditions
- Aging
- Keywords
- Histone, Chromatin, Epigenome, Senescence, Acetylation, Aging, Tissue Sample
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- 23 Sep 2008 (actual)
- Primary completion
- 4 May 2020 (actual)
- Study completion
- 5 Feb 2021 (actual)
- First posted
- 19 Oct 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine the role of epigenetics (heritable changes in gene function that occur without a change in DNA sequence) in the aging process. DNA is the primary genetic material, responsible for transmitting information from one cell to the next or from one generation to the next. A second layer of heredity is described by the term "epigenetics."
Epigenetic information is reset from one generation to the next. It works in two ways: 1) by modification of the DNA, like balloons stuck at irregular intervals onto the sides of the DNA helix that encodes genes, and 2) through specialized protein shells that wrap around some regions of DNA. As in DNA, these shells can copy themselves and can transmit instructions. Because they are used to turn genes on and off, errors in their settings cause critical misinformation to be transmitted.
Aging involves many changes, such as muscle weakening, graying hair, skin wrinkling, and so forth. There are several current theories of aging, including damage to genes by oxidation, shortening of tiny structures at the ends of chromosomes called telomeres, and the ability to stretch lifespan with caloric restrictions. This study will investigate the possible role of epigenetics in aging by examining and comparing the shell-like epigenetic settings in skin cells in young adults and older individuals. Preliminary results from earlier studies show differences in these settings in younger and older people.
Women between the ages of 21 and 30 years and 65 and 90 years who are undergoing breast reduction or mastectomy at Suburban Hospital in Bethesda, Maryland, may participate in this study. Tissue removed during surgery for pathological examination will also be used by researchers in this study to validate the preliminary findings noted above and to continue studies into the new area of epigenetics and aging.
...
Detailed description
Normal human lifespan is marked by a complex series of developmental events, relative stability during adulthood, and ultimately a gradual decline in viability. Biological clocks presumably underlie the developmental events that occur through childhood and adolescence, but the nature of those clocks has remained obscure. Progress in this area would be of considerable importance, not only for our understanding of child development, but also because instability in putative clock-like mechanisms may occur as part of the aging process. Such instability could well compromise tissue function and contribute to many of the common degenerative diseases of later life. We propose to investigate whether developmental clocks and related aspects of the aging process are attributable in part to age-related epigenome remodeling. Experiments done to date with cultured human fibroblasts derived from tissue banks provide tentative support for this hypothesis. To exclude tissue culture-related artifacts and to continue the work, it is essential to have access to fresh tissue material in the form of surgically obtained skin specimens that would otherwise be discarded. Elective breast reduction mammoplasty is a frequently performed surgery at Suburban Hospital, Bethesda, Maryland. Small skin specimens will be obtained from this procedure, as well as from normal skin derived from mastectomies. Patients who are to undergo these procedures will be asked to sign a consent form allowing the specimens, normally discarded, to be used instead for research on the mechanism of aging. They will be informed that clinical information will accompany the specimens, including age and known disease conditions. Twenty patients in each of two age ranges, 21-30 yr and 65-90 yr, will be enrolled in the study. The primary outcome will be confirmation of age-related epigenome change in the chromosome 4q35.2 region, previously documented using tissue bank-derived cultured skin fibroblasts. Mapping and sampling chromatin from this region revealed higher histone H4 acetylation in young (24-30 yr) than old (80-85 yr) individuals. Confirmation of this change in primary fibroblasts will be followed by more detailed mapping of chromatin structure and extension beyond the currently defined limits. Secondary outcomes will include examination of two areas of epigenome remodeling that appear to occur between birth and adulthood, as well as searches for additional regions of age-related chromatin change.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 14 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Neonatal cord blood samples collected in association with normal deliveries at a NICHD obstetrics service in Wayne State University (PI Dr. Roberto Romero). Adult samples collected from volunteers at the NIH Blood Bank.
Key inclusion criteria (3 listed)
- Age 21-30 or 65-90, female or male
- Normal liver function, renal function adjusted for age
- Written informed consent
Key exclusion criteria (4 listed)
- Down's or other premature aging syndromes
- Mastectomies: skin involvement in the malignant process or damage due to prior radiation therapy
- Active skin infection
- Skin damage due to photoaging will be noted but will not be a basis for exclusion
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Improved understanding of dynamic epigenome change and its roles in development and aging
Time frame: Cross-sectional study design with measures corresponding to collection time point
Publication of scholarly articles describing previously unknown modes of postnatal human epigenome change and their consequences for gene expression.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2021.
- Background: PubMed 15734681Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell. 2005 Feb 25;120(4):483-95. doi: 10.1016/j.cell.2005.02.001.
- Background: PubMed 14698809Bandyopadhyay D, Medrano EE. The emerging role of epigenetics in cellular and organismal aging. Exp Gerontol. 2003 Nov-Dec;38(11-12):1299-307. doi: 10.1016/j.exger.2003.09.009.
- Background: PubMed 11005794Bestor TH. The DNA methyltransferases of mammals. Hum Mol Genet. 2000 Oct;9(16):2395-402. doi: 10.1093/hmg/9.16.2395.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruce H Howard, M.D. principal investigator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Aging, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improved understanding of dynamic epigenome change and its roles in development and aging (time frame: Cross-sectional study design with measures corresponding to collection time point). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00242255, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2021.