Aging and the Germ Line: Where Mortality and Immortality Meet

Abstract

Germ cells are highly specialized cells that form gametes, and they are the only cells within an organism that contribute genes to offspring. Germline stem cells (GSCs) sustain gamete production, both oogenesis (egg production) and spermatogenesis (sperm production), in many organisms. Since the genetic information contained within germ cells is passed from generation to generation, the germ line is often referred to as immortal. Therefore, it is possible that germ cells possess unique strategies to protect and transmit the genetic information contained within them indefinitely. However, aging often leads to a dramatic decrease in gamete production and fecundity. In addition, single gene mutations affecting longevity often have a converse effect on reproduction. Recent studies examining age-related changes in GSC number and activity, as well as changes to the stem cell microenvironment, provide insights into the mechanisms underlying the observed reduction in gametogenesis over the lifetime of an organism.

Epigenetic regulation of aging stem cells

“…While this review will focus on stem cell aging in mammals, it is important to note that elegant studies in invertebrates have highlighted the changes in stem cell and niche during aging, and the mechanisms underlying some of these changes (Arantes-Oliveira et al, 2002;Boyle et al, 2007;Jones, 2007;Biteau et al, 2008). In mammals, age-related changes to stem cells and their niches may be broadly grouped into two classes: those that are irreversible versus reversible in nature (Figure 1).…”

Germline stem cell maintenance as a proximate mechanism of life‐history trade‐offs?

“…Despite the limited life span of individual stem cells, Drosophila females may produce eggs for over 2 months, suggesting that the lost GSCs can be replaced [21]. Histological observations show that the rate of GSC loss is significantly slower than it would be in the absence of stem cell replacement [13].…”

“…The second group of factors involves the interactions between diet and hormonal signaling [11,28,29]. Recently, both types of GSC-maintaining mechanisms have been found to decline naturally with age, suggesting that reduction in some of these signals may contribute to the loss of fecundity through aging [15,20,21,23,24]. In the following sections, we outline candidate local and systemic mechanisms (Fig.…”

Stem Cells, Their Niches and the Systemic Environment: An Aging Network

“…First, however, I will describe the correlation between organismal aging and stem cell aging and review the potential mechanisms involved in stem cell decline. GSCs proliferate more slowly and are gradually lost in aging Drosophila females and males ( Jones 2007). The numbers of HSCs, NSCs, or satellite cells do not appear to decline with age, but their activity becomes compromised (Geiger and Van Zant 2002;Conboy et al 2003;Hattiangady and Shetty 2008).…”

“…Many layers of regulation in response to local, systemic, and environmental factors govern stem cell behavior Morrison and Spradling 2008). Evidence from several systems also suggests that stem cell functional output is altered during aging (Rando 2006;Jones 2007;Sharpless and Depinho 2007), although causal relationships and molecular underpinnings are poorly understood. To effectively wield these double-edged swords for therapeutic interventions, it will be essential to further explore their regulation and function using the combined power of multiple model organisms.…”