Distinguishing between longevity and buffered-deleterious genotypes for exceptional human longevity: The case of the MTP gene

Derek M. Huffman; Joris Deelen; Kenny Ye; Aviv Bergman; Eline P. Slagboom; Nir Barzilai; Gil Atzmon

doi:10.1093/gerona/gls103

Distinguishing between longevity and buffered-deleterious genotypes for exceptional human longevity: The case of the MTP gene

Derek M. Huffman, Joris Deelen, Kenny Ye, Aviv Bergman, Eline P. Slagboom, Nir Barzilai, Gil Atzmon

Research output: Contribution to journal › Article › peer-review

Abstract

The single nucleotide polymorphism, rs2866164, in the MTP gene, has been associated with human longevity but has not been validated by subsequent longevity studies. Using our population of Ashkenazi Jews, we find that the MTP CC genotype is significantly overrepresented in centenarians and their offspring, as compared with controls (p <. 05). However, when we examined MTP CC genotype frequency pattern with aging, we observed a monotonic decline between ages 55-85 years followed by a dramatic enrichment after age 90 years, forming a U-shape pattern (p <. 05). Furthermore, the MTP CC genotype was buffered by three validated longevity genotypes (p <. 05). This buffering effect was found to confer an enrichment of the MTP CC genotype in centenarians, whereas their absence in CC controls resulted in poorer survivorship (p <. 05). Thus, we conclude that MTP CC is a buffered-deleterious genotype and that assessing genotype frequency across aging is essential for discerning longevity from buffered-deleterious genotypes.

Original language	English
Pages (from-to)	1153-1160
Number of pages	8
Journal	Journals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume	67
Issue number	11
DOIs	https://doi.org/10.1093/gerona/gls103
State	Published - Nov 2012
Externally published	Yes

Bibliographical note

Funding Information:
This work has been supported by grants from the Paul Beeson Physician Faculty Scholar in Aging Award, the Ellison Medical Foundation Senior Scholar Award, the General Clinical Research Center ( M01-RR12248 ), and the Diabetes Research and Training Center ( DK20541 ) at the Albert Einstein College of Medicine and grants AG027734, AG028872 , RR12248 , and M01RR12248 from the National Institutes of Health . D.M.H. is supported by an National Institute of Aging -sponsored K99 award (AG037574).

Keywords

Aging
Buffering mechanism
Genetics
Microsomal triglyceride transfer protein

ASJC Scopus subject areas

General Medicine

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10.1093/gerona/gls103

Cite this

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title = "Distinguishing between longevity and buffered-deleterious genotypes for exceptional human longevity: The case of the MTP gene",

abstract = "The single nucleotide polymorphism, rs2866164, in the MTP gene, has been associated with human longevity but has not been validated by subsequent longevity studies. Using our population of Ashkenazi Jews, we find that the MTP CC genotype is significantly overrepresented in centenarians and their offspring, as compared with controls (p <. 05). However, when we examined MTP CC genotype frequency pattern with aging, we observed a monotonic decline between ages 55-85 years followed by a dramatic enrichment after age 90 years, forming a U-shape pattern (p <. 05). Furthermore, the MTP CC genotype was buffered by three validated longevity genotypes (p <. 05). This buffering effect was found to confer an enrichment of the MTP CC genotype in centenarians, whereas their absence in CC controls resulted in poorer survivorship (p <. 05). Thus, we conclude that MTP CC is a buffered-deleterious genotype and that assessing genotype frequency across aging is essential for discerning longevity from buffered-deleterious genotypes.",

keywords = "Aging, Buffering mechanism, Genetics, Microsomal triglyceride transfer protein",

author = "Huffman, {Derek M.} and Joris Deelen and Kenny Ye and Aviv Bergman and Slagboom, {Eline P.} and Nir Barzilai and Gil Atzmon",

note = "Funding Information: This work has been supported by grants from the Paul Beeson Physician Faculty Scholar in Aging Award, the Ellison Medical Foundation Senior Scholar Award, the General Clinical Research Center ( M01-RR12248 ), and the Diabetes Research and Training Center ( DK20541 ) at the Albert Einstein College of Medicine and grants AG027734, AG028872 , RR12248 , and M01RR12248 from the National Institutes of Health . D.M.H. is supported by an National Institute of Aging -sponsored K99 award (AG037574).",

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AU - Slagboom, Eline P.

AU - Barzilai, Nir

AU - Atzmon, Gil

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N2 - The single nucleotide polymorphism, rs2866164, in the MTP gene, has been associated with human longevity but has not been validated by subsequent longevity studies. Using our population of Ashkenazi Jews, we find that the MTP CC genotype is significantly overrepresented in centenarians and their offspring, as compared with controls (p <. 05). However, when we examined MTP CC genotype frequency pattern with aging, we observed a monotonic decline between ages 55-85 years followed by a dramatic enrichment after age 90 years, forming a U-shape pattern (p <. 05). Furthermore, the MTP CC genotype was buffered by three validated longevity genotypes (p <. 05). This buffering effect was found to confer an enrichment of the MTP CC genotype in centenarians, whereas their absence in CC controls resulted in poorer survivorship (p <. 05). Thus, we conclude that MTP CC is a buffered-deleterious genotype and that assessing genotype frequency across aging is essential for discerning longevity from buffered-deleterious genotypes.

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Distinguishing between longevity and buffered-deleterious genotypes for exceptional human longevity: The case of the MTP gene

Abstract

Bibliographical note

Keywords

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