CAUSES OF AGING

Our science-backed products combat the 10 main causes of aging in several ways.

For us, understanding causes of aging is as important as combating its signs. While most anti-aging companies just target signs of aging, KOBHO also addresses their prevention to minimize risks.

KOBHO has selected the best and more bioavailable ingredients to tackle the 10 causes of aging. And the best doctors and the scientific studies support them.

Aging is a complex process involving loss of physiological integrity, which is associated to or responsible for age-related diseases. At the molecular level, it is characterized by the progressive accumulation of molecular damage.

Why do we age?
Recent research uncovered 10 hallmarks of aging:

  1. Cellular senescence
  2. Mitochondrial dysfunction
  3. Proteostasis lost
  4. Deregulated nutrient sensing
  5. Epigenetic alterations
  6. Genomic instability
  7. Telomere shortening
  8. Cross linking
  9. Altered intercellular communication
  10. Stem cell exhaustion

HALLMARKS OF AGING

Senescent cells are former healthy cells that stopped dividing, but do not die, and secrete substances that harm healthy cells around. In the short term, cellular senescence is a protective response of the human body against damage signals. Over time, these “zombie” cells accumulate in tissues, contributing to age-related organ dysfunction, and accelerating the aging process.

Substances that help the body to eliminate senescent cells (“senolytics”): quercetin

1. Cellular Senescence

As we age, mitochondria, the energy powerhouse of cells lose their functionality. Without enough energy, cells do not function properly, and consequently drop overall performance. Mitochondria also produces more oxidative substances, which damage cells and accelerates aging.

Substances that contribute to healthy mitochondrial function: alpha-lipoic acid, astaxanthin, magnesium, and vitamin C and E

2. Mitochondrial Dysfunction

Autophagy is a fundamental process in proteostasis that removes erroneous proteins. During aging, autophagy decreases and these proteins accumulate inside our cells and damage them. Proteostasis collapse contributes to the development of age-associated diseases.

Substances that contribute to the maintenance of cellular proteostasis: curcumin, resveratrol.

3. Proteostasis Loss

When we get older, nutrient sensing pathways of cells begin to disrupt, which affects how our cells produce energy. This leads to lack of power, which compromises appropriate cell functions and accelerates aging.

Substances that support nutrient metabolism: magnesium, resveratrol.

4. Deregulated Nutrient Sensing

Epigenome compounds that regulate our genes’ activity become gradually disrupted with age. It is enhanced by exposure to harmful environmental factors. Epigenetic changes affect the proper gene expression to turn genes on and off. This results in alteration of cell functions, which plays a crucial role in the development of age-related diseases.

Substances that prevent epigenetic alteration: vitamin A and C.

5. Epigenetic Alterations

This is an excessive damage accumulation of the genetic material being mitochondria the main target of aging-associated mutations. These damaged organelles begin to produce harmful substances that accelerate the process of premature aging and its associated diseases.

Substances that support genomic stability: magnesium.

6. Genomic Instability

As we age, the accumulated DNA damage leads to the progressive loss of telomeres - chromosomal end regions that contain your genetic material. Telomere exhaustion involves a decline of cell division capacity, and by extension, the regenerative capacity of tissues, which accelerates the development of age-related diseases.

Substances that support telomere preservation: astaxanthin and coenzyme Q10.

7. Telomere Shortening

As we age, sugar-derived glycation bonds or crosslinks adjacent proteins, which leads to a stiffening of proteins, and by extension of tissues. Cross links accumulate over the years outside cells, affecting the performance of blood vessels, skin, and tendons.

Substances that prevent glycation: curcumin and resveratrol.

8. Cross Linking

Changes in the communication among cells at various levels are associated to “inflammaging” (age-related low-grade inflammation). Exposure to inflammatory agents prevent cells, especially those involved at the endocrine and neuronal levels from performing their functions properly.

Substances that reduce “inflammaging”: curcumin.

9. Altered Intercellular Communication

Over time, stem cells become less functional or die, as a consequence of multiple age-related genetic damage. The regenerative capacity of tissues is exhausted, since there are no new stem cells in reserve.

Substances that support stem cell maintenance: resveratrol, niacinamida, vitamins A, B6, C, and E, and zinc.

10. Stem cell exhaustion

REFERENCES

Chaudhuri, J. et al. (2018) “The role of advanced glycation end products in aging and metabolic diseases: Bridging association and causality,” Cell metabolism, 28(3), pp. 337–352. doi: 10.1016/j.cmet.2018.08.014.

van Deursen, J. M. (2014) “The role of senescent cells in ageing,” Nature, 509(7501), pp. 439–446. doi: 10.1038/nature13193.

Diggs, J. (2007) “The cross‐linkage theory of aging,” in Encyclopedia of Aging and Public Health. Boston, MA: Springer US, pp. 250–252.

Gonzalo, S. (2010) “Epigenetic alterations in aging,” Journal of applied physiology (Bethesda, Md.: 1985), 109(2), pp. 586–597. doi: 10.1152/japplphysiol.00238.2010.

Hermann, R. et al. (1996) “Enantioselective pharmacokinetics and bioavailability of different racemic α-lipoic acid formulations in healthy volunteers,” European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences, 4(3), pp. 167–174. doi: 10.1016/0928-0987(95)00045-3.

Li, Z. et al. (2021) “Aging and age-related diseases: from mechanisms to therapeutic strategies,” Biogerontology, 22(2), pp. 165–187. doi: 10.1007/s10522-021-09910-5.

López-Otín, C. et al. (2013) “The hallmarks of aging,” Cell, 153(6), pp. 1194–1217. doi: 10.1016/j.cell.2013.05.039.

Roger, L., Tomas, F. and Gire, V. (2021) “Mechanisms and regulation of cellular senescence,” International journal of molecular sciences, 22(23), p. 13173. doi: 10.3390/ijms222313173.

Rossmann, M. P. et al. (2021) “Mitochondrial function in development and disease,” Disease models & mechanisms, 14(6). doi: 10.1242/dmm.048912.

Soto-Palma, C. et al. (2022) “Epigenetics, DNA damage, and aging,” The journal of clinical investigation, 132(16). doi: 10.1172/JCI158446.

Taylor, R. C. and Dillin, A. (2011) “Aging as an event of proteostasis collapse,” Cold Spring Harbor perspectives in biology, 3(5), pp. a004440–a004440. doi: 10.1101/cshperspect.a004440.

Wollin, S. D. and Jones, P. J. H. (2003) “Alpha-lipoic acid and cardiovascular disease,” The journal of nutrition, 133(11), pp. 3327–3330. doi: 10.1093/jn/133.11.3327.

von Zglinicki, T. and Martin-Ruiz, C. M. (2005) “Telomeres as biomarkers for ageing and age-related diseases,” Current molecular medicine, 5(2), pp. 197–203. doi: 10.2174/1566524053586545.