LITMIR.BIZ

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tree nuts, tea leaf, and some fruits.²³ It is possible to obtain spermidine from semen (at concentrations on a par with tree nuts), however the concentration of spermidine in legumes is 6-times greater than that obtainable from semen.

      Senescence

      Cell senescence is the irreversible loss of the ability of cells to divide. There are 2 types of senescence:

      1.Replicative senescence – exhaustion of proliferative lifespan over time (aging), shortened telomeres induce DNA damage;

      2.Stress-induced premature senescence (SIPS) – triggered by external stimuli, including oxidizing agents and radiation. SIPS is not usually characterized by telomere shortening.

      Due to the mechanism of DNA replication, telomeres shorten with each cell division. Although some cells (e.g. adult germ cells) contain specific enzymes, such as telomerase, that maintain telomere length. Increasing evidence suggests that telomere integrity rather than telomere length may be responsible for controlling cell longevity. However, there is also plenty of research documenting the importance of telomere length for longevity. For example, Carlquist et al found that telomere length predicted survival in patients referred for an angiogram.²⁴ The researchers studied data from 3,569 patients with a mean age of 63-years, approximately two-thirds were male and approximately two-thirds had coronary artery disease. Patients were followed for a total of 9-years, during which 1,122 died, 530 had a myocardial infarction, and 232 had a stroke. Study results showed that while telomere length was not associated with myocardial infarction or stroke, longer telomere length was associated with a decreased risk of death, even after adjustment for age and other risk factors. The researchers concluded: “Telomere length is a strong univariable predictor of survival that is not eliminated by adjustment for age and other risk factors.” So, we can see that telomere length is obviously important, however it is not the only issue with senescence. Oxidative stress causes premature senescence, but has absolutely nothing to do with telomere shortening. Senescence triggered by oxidative stress has numerous deleterious effects upon the cardiovascular system, including:

      •Endothelial senescence is associated with loss of function and a shift toward a proinflammatory and proapoptotic state²⁵;

      •Vascular smooth muscle cell (VSMC) senescence generates a proinflammatory environment, and VSMCs have a diminished ability to repair plaques²⁵;

      •Monocyte senescence generates a greater proinflammatory environment.²⁵

      We can see that premature senescence is clearly linked to arterial inflammation. Thus, premature senescence is bad news for our arteries and bad news if you want to live a long time. But can we do anything about it? Fortunately, we can.

      The best way to prevent premature senescence is to prevent oxidative stress. So, the first and foremost thing anyone should do if they want to prevent premature senescence is avoid nicotine as it increases oxidative stress.²⁶ Jha found that current smokers were 3-times more likely to die than people who had never smoked. Smokers were also found to lose at least 1 decade of life expectancy.²⁷ Thus, nicotine is not compatible with longevity. Exercise, CR, and antioxidants may also be helpful. Some medications, e.g. statins, angiotensin receptor blockers (ARBs), angiotensin-converting-enzyme (ACE) inhibitors, and possibly chloroquine, can also reduce oxidative stress, but again they have the potential for harm as well.

      CONCLUDING REMARKS

      If an anti-aging program is to be successful it needs to include therapies that will improve arterial health, enhance autophagy, and prevent premature senescence. Patients need to be encouraged to exercise every day. They need to eat a diet that is rich in antioxidants and spermidine, and which incorporates CR. They need to maintain their BMI between 20.0 and 24.9, and they need to endure that they remain sensitive to insulin. Finally, they need to avoid nicotine.

      The problem with placing patients on programs that involve them doing a lot of exercise and making major changes to their diet is compliance. If they can’t see any real benefits in the short-term they are likely to slip back into old habits. However, there is a simple and inexpensive urine test that can be used to measure oxidative stress, which we now know hampers autophagy, causes premature senescence, and drives arterial disease. F2-isoprostane testing enables us to objectively measure oxidative stress. The great thing about this is it enables patients to directly see the impact of all their hard work. This helps to motivate them and works wonders with compliance; it is also useful for identifying patients who perhaps are not exercising as often as they say they are. In short, the F2-isoprostane test is a very useful addition to a comprehensive anti-aging program.

      REFERENCES

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      13.Hubbard BP, Gomes AP, Dai H, et al. Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science. 2013;339:1216-1219. doi: 10.1126/science.1231097.

      14.Walle T, Hsieh F, DeLegge MH, Oatis JE Jr, Walle UK. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos. 2004;32:1377-1382.

      15.la Porte C, Voduc N, Zhang G, Seguin I, Tardiff D, Singhal N, Cameron DW. Steady-State pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol) in healthy human subjects. Clin Pharmacokinet. 2010;49:449-454. doi: 10.2165/11531820-000000000-00000.

      16.Carrizzo A, Puca A, Damato A, et al. Resveratrol Improves Vascular Function in Patients With Hypertension and Dyslipidemia by Modulating NO Metabolism. Hypertension. 2013 Jun 10. [Epub ahead of print]

      17.Harrison DE, Strong R, Sharp ZD, et al. Rapamycin fed late in life extends lifespan

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