Graceful Aging

For many people, the term aging can conjure images of thinning hair, night sweats, and hip replacements. But aging is a beautiful, reliable part of life that can be managed effectively by determining our genetic tendencies coupled with healthful lifestyle choices.


Some of the top concerns involved with aging are hormonal fluctuations and increased risk of fracture. In females, where risk of fracture is higher, hormones and fractures truly go hand in hand. As estrogen levels tend to decline in peri and post-menopause1, bone resorption increases.2 Changes in estrogen levels correlate with COMT breakdown of catecholestrogens. COMT is known to regulate and feedback on estrogen, playing a relevant role in hormone balance in aging. It is known that shifting androgens play a significant role in hair loss, but evidence points to the role of Vitamin D receptors modulating the hair growth cycle.

Single nucleotide polymorphism identification offers the advantage of reducing the rate of aging. One combination of SNP’s in particular gives us the benefit of supporting PREmenopausal women. WNT16 and ESR1-1 are two SNPs that have been found to be significantly associated with bone mineral density, particularly in the lumbar spine.3 Wnt16 is involved in the development of housing for vertebral and vascular smooth muscle precursors. SNPs in the WNT16 region have been associated with BMD and bone phenotypes at numerous skeletal sites.3 Studies have shown that bone diseases and disorders such as osteoporosis, sclerosteosis and van Buchem’s disease have been associated with aberrant WNT signaling.4,5 It is important to remark on the interaction of vitamin D receptors (VDR) and WNT signaling. 1,25D-VDR induces low density lipoprotein related protein which in turn potentiates WNT signaling resulting in proliferation of osteoblasts, emphasizing the role of VDR in bone health.6 Estrogen receptors (ESR1) encode a nuclear transcription factor believed to play a role in periosteal structure and growth. Gene wide association studies have linked ESR1 polymorphisms with changes in bone mineral density. The power of prevention is enhanced by assessing polymorphisms in the WNT and ESR1 genes.

With aging comes fluctuation in hormone levels. COMT, catechol-O-methyltransferase, is an integral part of degrading the catechol derivatives of estrogen as well as catecholamines. The COMT enzyme requires the presence of magnesium in order to degrade estrogen effectively. Research shows that serum estrogen levels are significantly affected by COMT status. Therefor the presence of COMT polymorphisms are involved, not only in estrogen balance, but also in the balance of dopamine and catecholamines in the aging process.

The hair growth cycle is governed by the status of androgen feedback on the follicle. In aging, the cycle shortens due to the activation of androgen receptors. The association between dihydrotestosterone and 5 alpha-reductase with hair loss is well known.7 A more novel concept is the role of vitamin D and the vitamin D receptor (VDR) in driving the mammalian hair cycle.6 Past research has emphasized the role of 1,25 hydroxyvitamin D3, the active D metabolite, in skin health. More recently, research has shown that 1,25(OH)2D3 induces expression of a β-catenin regulated gene which is required for not only epidermal differentiation but hair follicle differentiation. These studies have shown that VDR, through its role in 1,25(OH)2D3, promotes the ability of β-catenin to stimulate hair follicle differentiation and therefore hair follicle formation.8 VDR and vitamin D status may therefore play a role in the development of alopecia or hair loss.

With the aid of genetic polymorphism recognition, practitioners and their patients have the power to take a dynamic role in choosing to age gracefully by addressing genetic predispositions based on SNP testing. ESR and WNT status can determine the necessity of a plan for osteoporosis and fracture prevention. COMT status can help identify the need for hormone replacement therapy or hormone degradation support. Finally, vitamin D status, VDR and SNPs that affect 1,25(OH)2D3 production may play a role in age related alopecia. A close look at the inner workings of our DNA can provide tools to improve long-term health outcomes.

References

1. Su I.H, Freeman, E.W. Hormone changes associated with the menopausal transition. Minerva Ginecol. 2009;61(6):483-489.
2. Vaananen HK, Harkonen PL. Estrogen and bone metabolism. Maturitas. 1996;23(Suppl:)S65-9.
3. Koller D.L., Zheng H-F., et al. Meta-analysis of genome-side studies identifies WNT16 and ESR1 SNPs associated with bone mineral density in premenopausal women. J Bone Miner Res. 2013;28(3):547-558.
4. Kim et al. Wnt signaling in bone formation and its therapeutic potential for bone diseases. Ther Adv Musculoskel Dis. 2013; 5(1):13-31.
5. Medina-Gomez et al. Meta-Analysis of Genome-Wide Scans for Total Body BMD in Children and Adults Reveals Allelic Heteogeneity and Age-Specific Effects at the WNT16 Locus. PLoS Genet. 2012;8(7):e1002718.
6. Haussler M.R, Haussler C.A, et al. The nuclear vitamin D receptor controls the expression of genes encoding factors which feed the “Fountain of Youth” to mediate healthful aging. J Steroid Biochem Mol Ciol. 2010;121(1-2):88-97.
7. Ho C.H., Hughes J. Alopcia, Androgenetic. Treasure Island (FL): Statpearls Publishing; 2018.
8. Hu L, Bikle DD, Oda Y. Reciprocal Role of Vitamin D Receptor on β-Catenin Regulated Keratinocyte Proliferation and Differentiation. The Journal of steroid biochemistry and molecular biology. 2014;144PA:237-241. doi:10.1016/j.jsbmb.2013.11.002.
9. Palmer H.G, Anjos-Afonso F, et al. The Vitamin D Receptor Is a Wnt Effector that Controls Hair Follicle Differentiation and Specifies Tumor Type in Adult Epidermis. PLoSONE. 2008;