[Frontiers in Bioscience S5, 181-197, January 1, 2013]

Aging and male reproductive function: A mitochondrial perspective

Sandra Amaral1, Alexandra Amaral1, Joao Ramalho-Santos1,2

1CNC Center for Neuroscience and Cell Biology, University of Coimbra, Portugal, 2Department of Life Sciences, University of Coimbra, PO Box 3046, 3001-401 Coimbra, Portugal

TABLE OF CONTENTS

1.Abstract
2. Aging
3. Mitochondria and aging: the oxidative stress connection?
3.1. Age-related oxidative damage to mitochondrial macromolecules and bioenergetics
3.2. Uncoupling proteins, reactive oxygen species and aging
3.3. Imperfect turnover and aging
4. The male reproductive system
4.1. Mitochondria and male reproductive function
4.2. Mitochondria, oxidative stress and male infertility
5. Age and male reproduction: are mitochondria involved?
5.1. Changes in hormone levels and hypothalamus-pituitary-gonadal axis functionality
5.2. Changes in testicular architecture
5.2.1. Stem cell aging
5.2.2. Sperm and age associated male infertility
5.3. The role of reproductive tissues in lifespan modulation
5.4. Targets of intervention
6. Are mitochondria a link between aging and loss of fertility?
7. Acknowledgments
8. References

1. ABSTRACT

Researching the effects of aging in the male reproductive system is not trivial. Not only are multiple changes at molecular, cellular and endocrine levels involved, but any findings must be discussed with variable individual characteristics, as well as with lifestyle and environmental factors. Age-related changes in the reproductive system include any aspect of reproductive function, from deregulation of the hypothalamic-pituitary-gonadal axis and of local auto/paracrine interactions, to effects on testicular stem cells, defects in testicular architecture and spermatogenesis, or sperm with decreased functionality. Several theories place mitochondria at the hub of cellular events related to aging, namely regarding the accumulation of oxidative damage to cells and tissues, a process in which these organelles play a prominent role, although alternative theories have also emerged. However, oxidative stress is not the only process involved in mitochondrial-related aging; mitochondrial energy metabolism, changes in mitochondrial DNA or in mitochondrial-dependent testosterone production are also important. Crucially, all these issues are likely interdependent. We will review evidence that suggests that mitochondria constitute a common link between aging and fertility loss.

2. AGING