AGING THEORY: CAUSE 6: CELLULAR SENESCENCE

CELLULAR SENESCENSE-PRO

Added 1 Aug 2020 – Scientists recently discovered a way to preserve stem cells, which decrease as we age. Stem cells are necessary to replace differentiated cells that die from shortened telomeres, misfolded protein clumps, physical damage, etc. In particular, the immune system fails progressively from loss of stem cells to generate new immune response to viruses, cancer cells, etc. However, it has been found that the amount of alpha-ketoglutarate (AKG) in our bodies regulate whether stem cells survive, or differentiate which causes their loss.

Added 4 Aug 2021 – The Copenhagen City Heart Study (CCHS) is a prospective population study that included detailed questionnaires regarding participation in different types of sports and leisure-time physical activity. The 8577 participants were followed for up to 25 years. Multivariable-adjusted life expectancy gains compared with the sedentary group for different sports were as follows: tennis, 9.7 years; badminton, 6.2 years; soccer, 4.7 years; cycling, 3.7 years; swimming, 3.4 years; jogging, 3.2 years; calisthenics, 3.1 years; and health club activities, 1.5 years. See section on exercise.

24 July ’20 Science pg 373 – Alpha-ketoglutarate is an intermediate in the citric acid cycle. This cycle in all mitochondria is the way we generate ATP, which is the energy source for everything our body does.  “Perhaps alpha-ketoglutarate supplementation could promote a healthy lifespan in humans…” It promotes maintenance of stem cells, which usually decrease as we age, preventing regeneration of immune and other cells.

In a 2016 article, “It is a nitrogen scavenger and a source of glutamate and glutamine that stimulates protein synthesis and inhibits protein degradation in muscles. AKG as a precursor of glutamate and glutamine is a central metabolic fuel for cells of the gastrointestinal tract as well. AKG can decrease protein catabolism and increase protein synthesis to enhance bone tissue formation in the skeletal muscles and can be used in clinical applications. AKG not only extends lifespan, but also delays age-related disease (in worms).”

There is no known hazard. I am now taking 1g per day. It is inexpensive.

See also why removing senscent cells with senolytics may be hazardous.

Emerging senolytic agents derived from natural products
Cellular senescence is a hallmark of aging, it is a permanent state of
cell cycle arrest induced by cellular stresses. During the aging
process, senescent cells (SCs) increasingly accumulate in tissues,
causing a loss of tissue-repair capacity because of cell cycle arrest in
progenitor cells and produce proinflammatory and matrix-degrading
molecules which are known as the senescence-associated secretory
phenotype (SASP), and thereby contribute to the development of various
age-related diseases. Genetic evidence has demonstrated that clearance
of SCs can delay aging and extend healthspan. Senolytics, small
molecules that can selectively kill SCs, have been developed to treat
various age-related diseases – effective senolytic agents, such as
quercetin, fisetin, piperlongumine and the curcumin analog. Some of the
compounds have been validated in animal models and have great potential
to be pushed to clinical applications.

MUSCLE – Muscle is 45-50% of body mass. Until about age 30, muscle cells continue to divide so working out grows more muscle cells. After age 30, unused muscle cells turn into collagen, and new muscle cells cannot be replaced or produced. But strength training helps maintain muscle cells, and can make the cells larger, so muscles appear bigger. There is now a redox stress theory of aging, in contrast to the free radical theory. It suggests pairs of electrons oxidize molecules and damage signaling pathways. People with more oxidative damage have slower walking speeds, in fact gait is proportional to longevity – so walk faster if you can. Slow gait is associated with development of dementia and AD. Cells respond to exercise and produce antioxidant enzymes in response. Everyone loses muscle fibers as they age, but you can hypertrophy remaining fibers to appear more fit. Branched chain amino acids help maintain muscles. Sat’d fats damage and decrease muscles, while MUFA, PUFA and vegetable diet help maintain them.