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

Wednesday, March 1, 2017

Your Thoughts?


I have included my latest mystery/thriller - A CURE FOR THE LIVING - to my manuscripts page.
Thank you for your input to date on THE DAEDALUS PROJECT. All comments are very much appreciated.

Thanks,
Bill.

Friday, February 3, 2017

Epigenetic Markers for Cellular Aging

While there have been many hypotheses on the causes of ageing, the precise mechanism of cellular ageing, and how it can be measured, remains unclear.

A study in 2016 (1) has illuminated the differences between various measurements and possible mechanisms of cellular senescence and ageing.

One widely-reported association between telomere length and ageing has been proven to be inconsistent. Over-expression of oncogene, and DNA damage, have also been seen as contributing to cellular ageing. But the oncogene-induced senescence is really a tumor-suppressive mechanism. Oncogenes, which cause abnormal DNA replication, as well as short telomere length, are both detected by cellular mechanisms as damaged DNA and then initiate senescence of the cell.

Another change related to ageing is the level of methylation at some CpG sites. This has been developed by the authors as a tool for estimating chronological age. The study shows that this “epigenetic clock” measurement is much more accurate in measuring chronological age than telomere length, and correlates well with physical factors in the elderly.

The conclusion of this study is that epigenetic and chronological cellular ageing, as measured by CpG methylation, are independent of cellular senescence caused by telomere length or DNA damage. The results of this and other studies show that even if telomere length is artificially maintained by telomerase, the cell continues to age. The telomeres act as a mechanism for restricting the number of cellular divisions, not for preventing ageing. Cellular senescence, due to DNA damage, telomere shortening, oncogenes, or whatever, is merely a mechanism for removing cells that are seen as damaged, while the rest of the cells continue to age naturally. Cellular ageing “is an intrinsic mechanism that exists from the birth of the cell and continues” throughout its life. 

Which brings us to the larger questions of what causes cellular ageing. Do the methylation markers cause ageing, or does ageing from another source cause the methylation? It is known that methylation is a mechanism for turning certain genes on or off. Since each species has a specific life span, it is clear (at least to me), that each species has evolved a genetic mechanism for ageing and death at a precise moment. Methylation may be a mechanism for directing the cell to begin ageing.

One hypothesis for the specific rate of ageing of each species is that each species, in order to adapt to the rate of change of the environment in the niche it inhabits, developed at optimal time of reproduction. If the environment (food and water supply, weather, temperature, predators, etc.) changes quickly, the organism must adapt to reproduce quickly. It evolves a rapid rate of development to quickly reach sexual maturity and produce offspring with mutations better able to withstand the changes in the environment. Once reproductive maturity is reached, evolution can no longer exert an influence to keep the parent organism alive. In fact, there may even be evolutionary pressure for the parents to die off quickly in order to minimize competition with the offspring and thus increase their survival rate.

It is unclear to me, then, why so much money is currently being spent on researching what appear to be the consequences of ageing rather than focusing on the genetic process itself. DNA is a code, a very complicated code, but a code, nonetheless. Why not focus on breaking this code, and finding the obviously predetermined genetic cellular ageing mechanisms and limits on lifespan that each species has evolved?

We age and die because evolution could not function otherwise. But now we have reached a stage in our development where we no longer have to rely on natural evolution. Soon, hopefully, we will understand our genome to the extent that we will be able to control how we develop (and age). We will no longer be an evolving species, but a self-creating one. Of course, once we reach a stage where we no longer age, other problems will arise (reproductive, social, economic, political, psychological, etc.), as I have discussed in previous posts.


1.     Lowe, D. et al., Epigenetic clock analyses of cellular senescence and ageing, Oncotarget. 2016 Feb 23; 7(8): 8524–8531, https://dx.doi.org/10.18632%2Foncotarget.7383

Wednesday, June 8, 2016

Earth: One Of The Early Civilizations In The Universe

A paper in Monthly Notices of the Royal Astronomical Society in 2015 (1), based on data collected by NASA's Hubble Space Telescope and the Kepler space observatory, has arrived at some unexpected conclusions. The analysis suggests that earth was quite early in its formation as a habitable planet compared to all the habitable planets the universe will eventually produce.

Kepler's planet survey indicates that there are about 1 billion Earth-sized planets in the Milky Way galaxy at present. If you include the 100 billion galaxies in the observable universe, the number of Earth-like planets becomes exponentially larger. The Hubble volume (the volume of space containing all objects traveling away less than the speed of light due to the expanding universe) is estimated to contain about 10^20 Earth-like planets.

Calculations suggest that our solar system formed after 80% of the existing Earth-like planets in the Universe and the Milky Way had already formed. However, if the existing gas in the Universe continues to condense to form stars and planets, the analysis shows that the Earth formed before 92 per cent of similar Earth-like planets are expected to ever form in the future. In other words, there is less than an 8% chance that we are the only civilization the Universe will ever have.

But if we assume that the Milky Way today contains just one other civilization, calculations show that it is likely that Earth would be at least the ten billionth planet with a civilization in the observable Universe. The observable Universe would eventually contain at least one hundred billion civilizations.

If the calculations are right and most of the Earth-like planets in the Universe will form in the distant future, a civilization a trillion years from now will have a very difficult time in learning how the universe began and formed since most of the evidence for the big bang will have dissipated due to the accelerating expansion of the Universe. We may then consider ourselves lucky in being one of the “early” civilizations to form. 

If we are an early civilization, perhaps the only civilization in the Milky Way until now, though many more will eventually form, it might explain Fermi’s paradox, in which Enrico Fermi famously asked “Where is everybody?” in referring to why signs of extraterrestrial life haven’t yet been found. In the distant future we will be the the ones contacting their early civilizations, our own UFOs to be seen in their skies, and we will be imparting our knowledge of how the Universe formed since they would have no way of knowing.


1.     Peter Behroozi and Molly Peeples. On The History and Future of Cosmic Planet Formation. Monthly Notices of the Royal Astronomical Society, 2015 DOI: 10.1093/mnras/stv1817