Does a retrograde response in human aging and longevity exist?

G. De Benedictis, G. Carrieri, S. Garasto, G. Rose, O. Varcasia, M. Bonafè, C. Franceschi, S. M. Jazwinski

Research output: Contribution to journalArticle

Abstract

The retrograde response (RR) is a compensatory mechanism by which mutant strains of yeast are able to cope with mitochondrial DNA (mtDNA) impairments by up-regulating the expression of the stress-responder nuclear genes and significantly increasing lifespan. Starting from the observation that both mtDNA variability and Tyrosine hydroxylase (THO, stress-responder gene) variability are correlated with human longevity, we asked ourselves whether mechanisms similar to RR may exist in humans. As a first investigative step we have analyzed the distribution of the mtDNA inherited variants (haplogroups) according to THO genotypes in three sample groups of increasing ages (20-49 years; 50-80 years; centenarians). We found that the mtDNA haplogroups and the THO genotypes are associated randomly in the first group, while in the second group, and particularly in the centenarians, a non-random association is observed between the mtDNA and nuclear DNA variability. Moreover, in centenarians the U haplogroup is over-represented (p = 0.012) in subjects carrying the THO genotype unfavorable to longevity. On the whole these findings are in line with the hypothesis that longevity requires particular interactions between mtDNA and nuclear DNA and do not exclude the possibility that an RR has been maintained throughout evolution and it is present in higher organisms. (C) 2000 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)795-801
Number of pages7
JournalExperimental Gerontology
Volume35
Issue number6-7
DOIs
Publication statusPublished - 2000

Keywords

  • Human longevity
  • mtDNA haplogroups
  • Retrograde response

ASJC Scopus subject areas

  • Ageing
  • Medicine(all)

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    De Benedictis, G., Carrieri, G., Garasto, S., Rose, G., Varcasia, O., Bonafè, M., Franceschi, C., & Jazwinski, S. M. (2000). Does a retrograde response in human aging and longevity exist? Experimental Gerontology, 35(6-7), 795-801. https://doi.org/10.1016/S0531-5565(00)00169-8