Absence of the proapoptotic Bax protein extends fertility and alleviates age-related health complications in female mice.
The menopausal transition in human females, which is driven by a loss of cyclic ovarian function, occurs around age 50 and is thought to underlie the emergence of an array of health problems in aging women. Although mice do not undergo a true menopause, female mice exhibit ovarian failure long before death because of chronological age and subsequently develop many of the same age-associated health complications observed in postmenopausal women. Here we show in mice that inactivation of the proapoptotic Bax gene, which sustains ovarian lifespan into advanced age, extends fertile potential and minimizes many age-related health problems, including bone and muscle loss, excess fat deposition, alopecia, cataracts, deafness, increased anxiety, and selective attention deficit. Further, ovariectomy studies show that the health benefits gained by aged females from Bax deficiency reflect a complex interplay between ovary-dependent and -independent pathways. Importantly, and contrary to popular belief, prolongation of ovarian function into advanced age by Bax deficiency did not lead to an increase in tumor incidence. Thus, the development of methods for postponing ovarian failure at menopause may represent an attractive option for improving the quality of life in aging females.
Perez
Gloria I
GI
Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114, USA.
Jurisicova
Andrea
A
Wise
Lisa
L
Lipina
Tatiana
T
Kanisek
Marijana
M
Bechard
Allison
A
Takai
Yasushi
Y
Hunt
Patricia
P
Roder
John
J
Grynpas
Marc
M
Tilly
Jonathan L
JL
D000375:Aging / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D001823:Body Composition; D001842:Bone and Bones / Q000502:physiology; D003071:Cognition; D005260:Female; D005298:Fertility / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010052:Ovariectomy; D010053:Ovary / Q000473:pathology; D010465:Perception; D051028:bcl-2-Associated X Protein / Q000172:deficiency*
D051028:bcl-2-Associated X Protein