RT Journal Article
T1 Reduced expression of mitochondrial complex I subunit Ndufs2 does not impact healthspan in mice.
A1 McElroy, Gregory S
A1 Chakrabarty, Ram P
A1 D'Alessandro, Karis B
A1 Hu, Yuan-Shih
A1 Vasan, Karthik
A1 Tan, Jerica
A1 Stoolman, Joshua S
A1 Weinberg, Samuel E
A1 Steinert, Elizabeth M
A1 Reyfman, Paul A
A1 Singer, Benjamin D
A1 Ladiges, Warren C
A1 Gao, Lin
A1 Lopéz-Barneo, José
A1 Ridge, Karen
A1 Budinger, G R Scott
A1 Chandel, Navdeep S
AB Aging in mammals leads to reduction in genes encoding the 45-subunit mitochondrial electron transport chain complex I. It has been hypothesized that normal aging and age-related diseases such as Parkinson's disease are in part due to modest decrease in expression of mitochondrial complex I subunits. By contrast, diminishing expression of mitochondrial complex I genes in lower organisms increases lifespan. Furthermore, metformin, a putative complex I inhibitor, increases healthspan in mice and humans. In the present study, we investigated whether loss of one allele of Ndufs2, the catalytic subunit of mitochondrial complex I, impacts healthspan and lifespan in mice. Our results indicate that Ndufs2 hemizygous mice (Ndufs2+/-) show no overt impairment in aging-related motor function, learning, tissue histology, organismal metabolism, or sensitivity to metformin in a C57BL6/J background. Despite a significant reduction of Ndufs2 mRNA, the mice do not demonstrate a significant decrease in complex I function. However, there are detectable transcriptomic changes in individual cell types and tissues due to loss of one allele of Ndufs2. Our data indicate that a 50% decline in mRNA of the core mitochondrial complex I subunit Ndufs2 is neither beneficial nor detrimental to healthspan.
YR 2022
FD 2022-03-25
LK http://hdl.handle.net/10668/19595
UL http://hdl.handle.net/10668/19595
LA en
DS RISalud
RD Apr 7, 2025