Remarkable 36% Lifespan Extension in Female Mice When Given Ovary Transplant
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Our PubMed screening during February 2020 had several especially noteworthy papers to choose from to highlight in our blog. Ultimately however, we decided to focus on this report of a remarkable 36% extension of average female mouse lifespan when given an ovarian transplant in middle-age.
To better understand these experiments and their implications, we should briefly review some concepts in female reproductive biology. The two important concepts to understand are (1) the ovary, and (2) the germ cells. You should know that the ovaries are essentially the “housing system” for the germ cells. Primitive germ cells reside in the ovaries and—with the help of the ovaries—can develop into ova (egg cells).
The experiments in this study were done only in female mice. The investigators tested whether young, healthy ovaries affected lifespan when transplanted into middle-aged mice with poorly functioning ovaries. But they tested one more factor: does it matter whether the ovaries contained germ cells?
They found that any youthful ovarian tissue, if transplanted into old mice with dysfunctional ovaries, significantly extended lifespan. However, it was the germ-cell-depleted ovaries which caused the greater (36%) increase in average lifespan. Also note that mice receiving any youthful ovarian transplant experienced a reduction in age-related kidney dysfunction and a dramatic reduction in age-associated inflammation.
One obvious question to ask is “why do germ-cell-depleted ovaries cause a greater extension of lifespan?” One might think that transplanting additional youthful tissue (ovaries + germ cells vs. ovaries only) into old animals would cause a greater extension of lifespan. But this was not the case. The authors offered an explanation. They suggested that germ cells essentially “use up” ovary cell capabilities in the process of hormonal cycling for reproductive processes. Without germ cells, ovaries are not burdened with this hormonal cycling for germ cell development, and thus do not become exhausted as quickly. As a result, these ovaries have a longer period time to promote the healthy functioning of the organism, resulting in a greater extension of lifespan.
Also noteworthy was the age at which these experiments were done. For the sake of illustration, let’s translate these study results into human terms, even though doing so might reasonably be considered reckless considering the dramatic differences between mice and humans. Let’s assume an average human female lifespan of 80 years, and let’s use the percent of total lifespan as markers in this conversion (e.g. menopausal age of 55 years is at 55 out of 80 years, or occurs at 68.75% of the human lifespan). Finally, let’s use the mouse figures reported in this study: an average mouse lifespan of 644 days, with estropause (reproductive senescence) at 360 days (12 months), or at 55.9% of average lifespan.
Using these mouse-to-human equivalencies, this study basically transplanted ovaries from young, menstruating girls into 45-year-old, (relatively young) menopausal women. If the older women received germ-cell-depleted ovaries, they lived to an average age of 109 years instead of 80, and they lived to a maximum age of about 130 years. That’s quite the lifespan extension!
To be abundantly clear, these researchers did nothing of the kind, nor are we advocating any such type of experiment be attempted. Moreover, the age translations between mice and humans performed above are not perfect (45 is quite early for human menopause, and human females usually don’t menstruate by age 7). But these translations help put the magnitude of the positive effect into perspective. Such a large, positive effect on lifespan suggests that the reproductive organs may influence an under appreciated proportion of healthy lifespan. We’re curious whether a similar effect might be seen in testicular transplants from young male mice to older male mice.
Recall the authors’ suggestion that the cyclic nature of germ cell recruitment may deplete the life-sustaining capability of healthy ovarian tissue. This raises the question: could some modern hormonal contraceptives extend human female lifespan by preventing the hormonal cycling associated with ovulation, menstruation—and apparently—depletion of ovarian function? Perhaps we will one day find out.
In any case, we found this study remarkable partly because of the magnitude of the lifespan extension, and partly because it was apparently mediated by something other than the usual interference with growth hormone/IGF-1 or mTOR signaling so often seen in successful lifespan extension studies in rodents (and other organisms). These results suggest that, at least in females, ovarian function may affect healthspan and lifespan to a greater extent than is usually appreciated at the present time.