Advances in endocrinology of aging research, 2005–2006

Abstract

The purpose of this brief review is to highlight some of the more important advances in endocrinology of aging research over the past year. Four advances were chosen and briefly described. First, exploration of the early steps in the generation of the internal steroidal hormonal signal involved in lifespan extension via the insulin/IGF-like signaling pathway in the nematode by two research groups revealed that the product of cholestanoic acid derivatives metabolized by a cytochrome P-450-like protein activates a protein with homology to the mammalian nuclear receptor superfamily, a process strikingly similar to the steroid hormone signaling pathway documented in mammalian systems. Second is the discovery that sirtuins, proteins that regulate lifespan in model organisms, enhance pancreatic insulin secretion in mice following a glucose challenge, suggesting the potential to regulate mammalian lifespan through regulation of the insulin signaling pathway. Third, the newly discovered hormone klotho, which also plays a role in regulating lifespan, in this case in mice, is reported to not only negatively affect insulin sensitivity but, perhaps more importantly, significantly affects calcium and phosphate metabolism as a required co-factor of Fgf-23 signaling. Finally the gonadotropin FSH is shown to directly affect bone density in mice separate from any direct effect of estrogen, suggesting that reproductive hormones other than estrogen can directly impact menopause-associated pathophysiology in non-reproductive tissues. Keywordsendocrinology of aging; steroidal signaling; cholestanoic acid; sirtuins; insulin secretion; insulin signaling; klotho; gonadotropins; FSH; bone cells; bone density; model organisms Research on endocrinology of aging is quite broad, extending from mechanisms underlying the age-related declines in sex steroid and peptide reproductive and growth hormones, through male and female reproductive aging, and into pathophysiologic effects of age-altered hormone levels on somatic and neuronal tissues and the effects of treatment with exogenous hormones to ameliorate the health declines associated with aging. Several fascinating new or progressing areas of endocrinology of aging research came to light over the past year from about mid-2005 through about mid-2006. This is one perspective, not meant to be a complete survey of all of the research conducted in the area of endocrinology of aging over the past year. Certainly many readers will have their own selection of the highlights over this past year that will differ in whole or in part from those summarized here.Specific areas covered in this brief review are new and exciting findings regarding 1) identification of steroidal ligands involved in hormonal regulation of the lifespan-determining pathway in the nematode model, 2) new findings related to the role of factors involved in * present address: 4899 Elmer Derr Rd.,

The lifespan-promoting effect of acetic acid and Reishi polysaccharide

“…The sirtuin Table 2 List of differentially expressed proteins in C. elegans treated with acetic acid and Reishi polysaccharide fraction RF3 Spot Protein name family can enhance pancreatic insulin secretion in mice following a glucose challenge, suggesting again the potential to regulate mammalian lifespan through the insulin signaling pathway. 42 To date, these two signaling systems coupled with dietary restriction appear to account for the lifespan in most experimental organisms. 43 To ask whether the aging and longevity pathways described above can be used to evaluate the anti-aging activity of herbal mushrooms and vinegars, we have carried out a series of investigations and discovered that the lifespan-promoting effect of RF3 and acetic acid is based on their action on the signaling pathways of longevity.…”

Endocrine function in naturally long-living small mammals

“…McShane and Wise (1996) proposed that this extension of reproductive lifespan results from the preservation of the neuroendocrine axis since gonadotrophin secretions were sustained and even enhanced with caloric restriction while those in age-matched controls showed a decline in luteinizing hormone (LH) concentration and pulse amplitude. Age-related hypothalamic and pituitary changes may also be directly involved in reproductive cessation and non-reproductive menopausal effects, such as the cognitive decline associated with menopause (Bellino 2006). Both LH and follicle stimulating hormone (FSH) as well as hypothalamic gonadotrophin releasing hormone (GnRH) may affect cognition and beta amyloid induced neurofibrillary tangle development (Bowen et al, 2004) and LH suppression in an aged transgenic mouse model for Alzheimer’s disease markedly reduced beta amyloid deposition and the decline in cognitive function (Casadesus et al, 2006).…”

Evolutionary ecology of endocrine‐mediated life‐history variation in the garter snake Thamnophis elegans

“…The endocrine system is critically involved in the determination of fundamental life-history traits involved in evolutionary fitness, such as growth, reproduction, and even, as recent studies have indicated, aging and lifespan (e.g., Sinervo and Licht 1991, Flatt et al 2005, Bellino 2006. Life-history theory has long focused on how constraints involved in allocation of energy and other resources create tradeoffs among life-history traits both within and among taxa (Kirkwood 1977, Roff 1992, Stearns 1992, Charlesworth 1994.…”