Linking Stem Cells, Insulin Metabolism, and Aging

Reason
 
Issue CCLXVI - November 23, 2010
Recommend this page.
A sample image

It is an unfortunate fact of life that some people are dealt a better hand by chance and happenstance. This includes the biology we are born with, and its contributions to our life expectancy: for example, some people have better mitochondrial DNA than others, which does seem to be correlated with inherited longevity.

By way of a different example, let me point out recent research that shows a correlation between better insulin metabolism and inherited longevity. You might look back into the Fight Aging! archives for an introduction to insulin and its relationship with aging. It's a much-studied area:

Mainstream research on the biochemistry of aging and longevity - with an eye to slowing down aging rather than repairing it - is at this time primarily focused on a small number of areas. One is the cluster of mechanisms and signaling pathways associated with insulin and insulin-like growth factor 1 (IGF-1). You might recall that a tenfold increase in nematode life span was engineered via manipulation of IGF-1, for example.

Here is the research paper that caught my eye. The authors look at insulin sensitivity in long-lived families - how well the body's glucose metabolism operates, and whether that correlates well with longevity.

Familial longevity is marked by enhanced insulin sensitivity:

Insulin resistance is a risk factor for various age related diseases. In the Leiden Longevity study, we recruited long-lived siblings and their offspring. Previously we showed that, compared to controls, the offspring of long-lived siblings had a better glucose tolerance. Here, we compared groups of offspring from long-lived siblings and controls for the relation between insulin and glucose ... After adjustment for sex, age and fat mass, the insulin-mediated glucose disposal rate was higher in offspring than controls ... Furthermore, glucose disposal rate was significantly correlated with the mean age of death of the parents. In conclusion, offspring from long-lived siblings are marked by enhanced peripheral glucose disposal. Future research will focus on identifying the underlying biomolecular mechanisms, with the aim to promote health in old age.

Folk like you and I do in fact have a great deal of control over the course of our own insulin and glucose metabolisms. We can laze around and grow fat, or we can exercise and eat a diet that keeps us thin - type 2 diabetes, and the unseen biochemical damage that precedes it, is largely a choice. The Leiden offspring have a helping hand in this game in comparison to the rest of us, but it is only a helping hand, not a get out of jail free card. They can still damage themselves and become diabetic if they choose to take poor care of their health.

To me, it has long seemed that one of the more noble goals of longevity science is to make all the human variability in DNA and metabolism irrelevant when it comes to our life spans. Medicine of the near future will add far more healthy years to life - and far greater resistance to age-related disease - than even the best natural human metabolism. Longevity-enhancing therapies will make it possible for even the most genetically disadvantaged people to live in youthful vigor for far, far longer than we presently can.

Here is an open access paper that looks at stem cells, insulin signaling processes, and aging. In short, the activity of stem cells is vital to your long-term health, but this activity declines with age - and this decline is linked to other age-related changes, such as in insulin metabolism:

Tissue and organ rejuvenation and senescence/aging are closely related to the function of stem cells. Recently, we demonstrated that a population of [pluripotent] very small embryonic-like stem cells (VSELs) resides in the adult murine bone marrow (BM) and other murine tissues. We hypothesize that these pluripotent stem cells play an important role in tissue/organ rejuvenation, and have demonstrated that their proliferation and potentially premature depletion is negatively controlled by epigenetic changes of some imprinted genes that regulate insulin factor signaling.

...

Since the attenuation of insulin/insulin growth factor (Ins/Igf) signaling positively correlates with longevity, we propose, based on our experimental data, that gradual decrease in the number of VSELs deposited in adult tissues, which occurs throughout life in an Ins/Igf signaling-dependent manner, is an important mechanism of aging. In contrast, a decrease in Ins/Igf stimulation of VSELs that extends the half life of these cells in adult organs would have a beneficial effect on life span. Our preliminary data in long-living Igf-1-signaling-deficient mice show that these animals possess a 3-4 times higher number of VSELs deposited in adult BM, lending support to this novel hypothesis.

The big picture here is that mammals have evolved a balance of mechanisms to (a) repair themselves, and (b) suppress cancer. Crudely, we might think of cancer as being caused by damaged repair mechanisms run amok. The loss of repair capacity with age - which involves stem cell populations being reduced in number or becoming inactive due to changes in signaling processes - is a way to reduce the risk of cancer. This loss of stem cell capacity is coordinated by changes in the controlling systems of our biology: responses to accumulated damage and dysfunction, for example.

Thus, we should not be surprised to find that longer-lived animals of a given species have a greater regenerative capacity: more stem cells, or more active stem cells, or both. Nor should we be surprised to find out that known biochemical changes associated with longevity are a part of the controlling systems for stem cell behavior.

It is clearly the case that the evolved present state of many species is not optimized for longevity, but individuals have the capacity for longer lives if their metabolism ran slightly differently. Life spans are more plastic than was thought even a few decades ago: members of a smaller mammalian species like mice can live 30% longer if calorie restricted, and a change to their insulin metabolism can achieve the same end. There are survival advantages for a species that can more easily evolve into different lengths of life, better allowing it to prosper even if the environment changes dramatically.


Recommend this page.

This TRA feature has been edited in accordance with TRA's Statement of Policy.

Click here to return to TRA's Issue CCLXVI Index.

Learn about Mr. Stolyarov's novel, Eden against the Colossus, here.

Read Mr. Stolyarov's comprehensive treatise, A Rational Cosmology, explicating such terms as the universe, matter, space, time, sound, light, life, consciousness, and volition, here.

Read Mr. Stolyarov's four-act play, Implied Consent, a futuristic intellectual drama on the sanctity of human life, here.