Reference SummarySnyder JM, Geroscience 2023;45(1):385-397

Title

 Canagliflozin retards age-related lesions in heart, kidney, liver, and adrenal gland in genetically heterogenous male mice.

Authors

 Snyder JM; Casey KM; Galecki A; Harrison DE; Jayarathne H; et al.

Journal

 Geroscience

Volume

 45

Issue

 1

Year

 2023

Pages

 385-397

Abstract

 Canagliflozin (Cana), a clinically important anti-diabetes drug, leads to a 14% increase in median lifespan and a 9% increase in the 90th percentile age when given to genetically heterogeneous male mice from 7 months of age, but does not increase lifespan in female mice. A histopathological study was conducted on 22-month-old mice to see if Cana retarded diverse forms of age-dependent pathology. This agent was found to diminish incidence or severity, in male mice only, of cardiomyopathy, glomerulonephropathy, arteriosclerosis, hepatic microvesicular cytoplasmic vacuolation (lipidosis), and adrenal cortical neoplasms. Protection against atrophy of the exocrine pancreas was seen in both males and females. Thus, the extension of lifespan in Cana-treated male mice, which is likely to reflect host- or tumor-mediated delay in lethal neoplasms, is accompanied by parallel retardation of lesions, in multiple tissues, that seldom if ever lead to death in these mice. Canagliflozin thus can be considered a drug that acts to slow the aging process and should be evaluated for potential protective effects against many other late-life conditions.

Links

 J:336113 – MGI References
35974129 – National Library of Medicine/PubMed

Strain Notes

Strain Note
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 The mice used in this study were from 3 different colonies: TJL (40 female, 40 male), UM (42 female, 34 male), and UT (32 female, 40 male).
These "mice are bred as the progeny of (BALB/cByJ X C57BL/6 J)F1 mothers (JAX #100,009) and (C3H/HeJ X DBA/2 J)F1 fathers (JAX #100,004)".

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Adrenal gland - Cortex hyperplasia Adrenal gland - Cortex

0
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Adrenal gland - Cortex hyperplasia
  • canagliflozin (Cana)
 Adrenal gland - Cortex

0
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Adrenal gland - Cortex neoplasm Adrenal gland - Cortex

0 - 26
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Adrenal gland - Cortex neoplasm
  • canagliflozin (Cana)
 Adrenal gland - Cortex

6.7 - 7.7
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Adrenal gland - Subcapsular cell hyperplasia - spindle cell Adrenal gland - Subcapsular cell

0
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Adrenal gland - Subcapsular cell hyperplasia - spindle cell
  • canagliflozin (Cana)
 Adrenal gland - Subcapsular cell

0
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Blood neoplasia Blood

14 - 31
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Blood neoplasia
  • canagliflozin (Cana)
 Blood

13 - 31
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Blood vessel hemangiosarcoma Blood vessel

7.3 - 7.8
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Blood vessel hemangiosarcoma
  • canagliflozin (Cana)
 Blood vessel

5.1 - 14
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Liver - Hepatocyte hyperplasia Liver - Hepatocyte

9.1 - 24
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Liver - Hepatocyte hyperplasia
  • canagliflozin (Cana)
 Liver - Hepatocyte

6.8 - 17
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Liver foci Liver

3.6 - 14
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Liver foci
  • canagliflozin (Cana)
 Liver

5.1 - 7.9
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Liver hepatocellular adenoma Liver

7.3 - 9.8
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Liver hepatocellular adenoma
  • canagliflozin (Cana)
 Liver

8.5 - 16
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Liver hepatocellular carcinoma Liver

1.8 - 7.8
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Liver hepatocellular carcinoma
  • canagliflozin (Cana)
 Liver

1.7 - 4.8
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Lung adenoma Lung

11 - 31
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Lung adenoma
  • canagliflozin (Cana)
 Lung

14 - 27
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Lung carcinoma Lung

1.8 - 12
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Lung carcinoma
  • canagliflozin (Cana)
 Lung

5.1 - 7.9
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Lung hyperplasia Lung

16 - 24
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Lung hyperplasia
  • canagliflozin (Cana)
 Lung

22 - 30
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Ovary cyst Ovary

0
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Ovary cyst
  • canagliflozin (Cana)
 Ovary

0
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Ovary hyperplasia Ovary

0
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Ovary hyperplasia
  • canagliflozin (Cana)
 Ovary

0
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Pancreas - Islet of Langerhans hyperplasia Pancreas - Islet of Langerhans

27 - 78
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Pancreas - Islet of Langerhans hyperplasia
  • canagliflozin (Cana)
 Pancreas - Islet of Langerhans

28 - 69
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Thyroid gland - Follicular cell adenoma Thyroid gland - Follicular cell

0 - 6.5
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Thyroid gland - Follicular cell adenoma
  • canagliflozin (Cana)
 Thyroid gland - Follicular cell

0
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Thyroid gland - Follicular cell hyperplasia Thyroid gland - Follicular cell

4.3 - 11
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Thyroid gland - Follicular cell hyperplasia
  • canagliflozin (Cana)
 Thyroid gland - Follicular cell

14 - 24
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Uterus - Endometrium hyperplasia - cystic Uterus - Endometrium

0
(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Uterus - Endometrium hyperplasia - cystic
  • canagliflozin (Cana)
 Uterus - Endometrium

0