Fig. 1: Armh4 deficiency promotes healthy aging and extends longevity in mice.

a The level of circulating ARMH4 decreased in aged people compared with young adults detected by mass spectrometry²³. Data are presented as mean values +/- SEM. Black circles represent individual data points for n = 3 independent subjects. b The analysis of the public GTEx database about ARMH4 expression in blood samples from individuals aged 70-79 years compared to those aged 20-29 years. Young group are presented as box plots showing the median (0.0123), the 25th (0.0080) and 75th (0.0199) percentiles, and the minimum (0.0000) and maximum (0.0749) values, n = 69 (20–29); Old group are presented as box plots showing the median (0.0096), the 25th (0.0000) and 75th (0.0138) percentiles, and the minimum (0.0000) and maximum (0.0266) values, n = 26 (70–79). c The protein levels of Armh4 in the brain, lung, heart, liver, kidney and muscle from young (2–month-old) and aged (25-month-old) mice measured by western blot. Representative blot of n = 3 independent mice. Data are presented as mean values +/- SEM. Black circles represent individual data points for n = 3 independent mice. d Schematic diagram illustrating the Armh4 gene knockout (KO) strategy in mouse. e Validation of Armh4 KO at the mRNA level in mouse tissues using qRT-PCR. Data are presented as mean values +/- SEM. Black circles represent individual data points for n = 5 independent mice. f Mendelian inheritance of the breeding offspring from heterozygous Armh4-KO mice. g Representative images showing fur appearance of wild type (WT) and Armh4-KO mice at 2 months (young) or 25 months (aged) of age. Scale bar, 1 cm. h Weights of WT and Armh4-KO mice during natural aging. Data are presented as mean values +/- SEM, with sample sizes of n = 12/9, 11/9, and 8/9 (WT/KO) for the 6–15, 18–21, and 24-month groups, respectively. i Representative Masson’s trichrome staining images showing the infrastructure of skins from young/aged WT and Armh4-KO mice. n = 3. Scale bar, 200 μm. j Representative images showing the hair regeneration capacity after excising a patch of dorsal fur from 21-month-old WT or Armh4-KO mice. n = 3. Scale bar, 1 cm. k, l Survival curves of two panels of WT and Armh4-KO mice under natural feeding conditions. The mice from the first panel (k) were euthanized at 25 months of age for molecular studies, while mice from the second panel (l) were further raised until natural death. Statistical significance was determined by a two-tailed unpaired t-test, and the exact P values are reported directly on the figures. Source data are provided as a Source Data file.