The pineal aging and death program: life prolongation in pre-aging pinealectomized mice

Ann N Y Acad Sci. 2005 Dec:1057:133-44. doi: 10.1196/annals.1356.008.


A precise temporal program for growth, fertility, aging, and death exists in the "pineal complex" of the brain. It tracks, like a "clock," the ontogenetic phases of our life program. Transplantation of a very old pineal gland into the thymus or under the kidney capsule of a young mouse produces acceleration of aging and early death. We investigated the existence of such an inner biological clock on the assumption that a time exists in the pineal program when the pineal gland actively starts to deliver aging and death "signals" to the body, thus accomplishing its genetically inscribed sequence. Groups of BALB/c male or female mice were surgically pinealectomized (PX) at the age of 3, 5, 7, 9, 14, and 18 months, and their life span was evaluated. Periodical measurements of blood and hormonal and metabolic parameters were taken. Results showed that while PX at the age of 3 and 5 months promotes acceleration of aging, no relevant effect of PX is observed in mice PX at 7 or 9 months of age. On the contrary, a remarkable life prolongation was observed when mice were PX at the age of 14 months. No effects were seen when the mice were PX at 18 months of age. The same aging-promoting or -delaying effects were confirmed in the hematological and hormonal-metabolic values measured. The findings demonstrate the existence of an evolutionary-developmental role for the pineal complex during growth, fertility, and aging. The dominant role of the pineal in the initiation and progression of aging as a death signal is clear, but its nature and mechanism are totally unknown. In fact new experiments showed that an additional pineal gland from a young donor, when grafted into a young mouse, induces acceleration of aging. The significance of these intriguing findings is discussed.

MeSH terms

  • Age Factors
  • Animals
  • Biological Clocks / physiology
  • Death*
  • Female
  • Leukocytes / metabolism
  • Longevity*
  • Lymphocytes / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Pineal Gland* / metabolism
  • Pineal Gland* / surgery
  • Survival Rate
  • Thyroid Hormones / blood
  • Tissue Transplantation
  • Triglycerides / blood
  • Zinc / blood


  • Thyroid Hormones
  • Triglycerides
  • Zinc