Friday, April 5, 2019

The Slow Progress in Aging Research

In previous posts, I reported on studies in 2005 suggesting that infusing young blood into old mice can reverse the aging process. A follow-up study suggested that old blood may cause young mice to age faster, but young blood infused into old mice cannot rejuvenate them. In this 2016 study (1), researchers infused young blood into old mice and found no positive effect. When they infused old blood into young mice, however, researchers found that various organs tested, such as liver cell development, brain cell development, muscle strength and muscle tissue repair, all degenerated and aged to a much faster degree. Their conclusion was that old blood contains inhibitors that cause tissues to age. The previous findings of young blood causing old mice to rejuvenate may have been caused by diluting the old blood with young blood, and thus diluting the ‘aging’ molecules in the old blood.

Since the original 2005 studies, a great deal of effort has been put into trying to identify the molecules in the blood that may affect the aging process. A 2017 study (2) suggested that osteocalcin, a hormone produced by bone cells and which declines with age, can reverse age-related memory loss in mice. In a 2018 study at Harvard Medical School (3), researchers showed that sirtuin1, or SIRT1, a protein in endothelial cells of blood vessels decreases with age. If these, and associated proteins, are administered, the endothelial cells rejuvenate and reverses the aging process of the vascular system. This resulted in markedly increased muscle function and exercise capacity in mice. Another study in 2018 (4) found that the addition of certain chemicals targeting mitochondria reversed the aging process. Still another study (5) showed that MANF, (mesencephalic astrocyte-derived neurotrophic factor), which regulates metabolism and immune response, and which declines with age, can slow liver aging in mice and improve age-related metabolic dysfunction.

These and other studies (6) focus on specific organ systems to try to identify factors that are involved in the aging process. However, the hope of researchers is that a day will come when a unifying, global genetic answer can eventually be found that controls the aging process of the entire body, which can then be used to significantly extend a healthy human lifespan. At this pace of research, that day seems to be still a way off. 

  1. Justin Rebo, Melod Mehdipour, Ranveer Gathwala, Keith Causey, Yan Liu, Michael J. Conboy, Irina M. Conboy. A single heterochronic blood exchange reveals rapid inhibition of multiple tissues by old bloodNature Communications, 2016; 7: 13363 DOI: 10.1038/NCOMMS13363
  2. Gerard Karsenty et al. Gpr158 mediates osteocalcin’s regulation of cognition. Journal of Experimental Medicine, August 2017 DOI: 10.1084/jem.20171320
  3. Abhirup Das, George X. Huang, Michael S. Bonkowski, Alban Longchamp, Catherine Li, Michael B. Schultz, Lynn-Jee Kim, Brenna Osborne, Sanket Joshi, Yuancheng Lu, Jose Humberto Treviño-Villarreal, Myung-Jin Kang, Tzong-tyng Hung, Brendan Lee, Eric O. Williams, Masaki Igarashi, James R. Mitchell, Lindsay E. Wu, Nigel Turner, Zolt Arany, Leonard Guarente, David A. Sinclair. Impairment of an Endothelial NAD -H 2 S Signaling Network Is a Reversible Cause of Vascular Aging. Cell, 2018; 173 (1): 74 DOI: 10.1016/j.cell.2018.02.008
  4. Eva Latorre, Roberta Torregrossa, Mark E. Wood, Matthew Whiteman, Lorna W. Harries. Mitochondria-targeted hydrogen sulfide attenuates endothelial senescence by selective induction of splicing factors HNRNPD and SRSF2. Aging, 2018; DOI: 10.18632/aging.101500
  5. Pedro Sousa-Victor, Joana Neves, Wendy Cedron-Craft, P. Britten Ventura, Chen-Yu Liao, Rebeccah R. Riley, Ilya Soifer, Nicholas van Bruggen, Ganesh A. Kolumam, Saul A. Villeda, Deepak A. Lamba, Heinrich Jasper. MANF regulates metabolic and immune homeostasis in ageing and protects against liver damage. Nature Metabolism, 2019; DOI: 10.1038/s42255-018-0023-6
  6. Young-min Han, Tatiana Bedarida, Ye Ding, Brian K. Somba, Qiulun Lu, Qilong Wang, Ping Song, Ming-Hui Zou. β-Hydroxybutyrate Prevents Vascular Senescence through hnRNP A1-Mediated Upregulation of Oct4. Molecular Cell, 2018; DOI: 10.1016/j.molcel.2018.07.036