A group of scientists from Tbilisi State University in close cooperation with the scientists of the Institute of Physics have been studying the genetic aspects and pathologies of aging. Their work also focuses on finding ways to prevent age-related pathologies and to apply the general mechanisms of aging toward prolonging life.
The aging process is programmed in the genome of each organism and is manifested late in life. Any change in normal homeostasis, particularly any further loss of the cell function with aging, occurs in the functional units of the chromatin domains.
Modification of the chromatin structure and function by hetero- or deheterochromatinization occurs throughout life and plays a pivotal role in the irreversible process in aging by affecting gene expression, replication, recombination, mutation, repair, and programming (Gilson and Magdinier 2009
Heterochromatin is divided into two main forms according to their distinct structural functional dynamics: constitutive heterochromatin (CH) and facultative heterochromatin (FH). CH refers to the regions that are always maintained as heterochromatin; these span large portions of the chromosome and have a structural role. CH regions contain few genes and are located primarily in pericentromeric regions and telomeres. FH refers to those regions that can be formed as heterochromatin in a certain situation but can revert to euchromatin once required. FH can span from a few kilobases to a whole chromosome and generally includes regions with a high density of genes (Prokofieva-Belgovskaya 1986
; Vaquero 2009
We have used differential scanning microcalorimetry to produce a calorimetric curve in cultured human lymphocytes over the temperature range 38–130°C (Monaselidze et al. 2006
). The heating process produced clear and reproducible endothermic heat absorption peaks. We found that an endothermic peak at Tm
= 104 ± 1°C corresponds to melting of 30 nm-thick fibers, which represents the most condensed state of chromatin in interphase nuclei (heterochromatin), and that an endothermic peak at 96 ± 1°C corresponds to melting of 10 nm-thick filaments (euchromatin or chromatin). The chromatin heat absorption peaks VI and VII changed significantly with age. In particular, in the shifted endotherms VI and VII, the temperatures increased by 2°C and 3°C accordingly in old age (80–86 years). Additional condensation of the eu- and heterochromatin was demonstrated by an increase in Tm
by 2 and 3°C in comparison with the meddle age (25–40 years). These prominent changes in chromatin stability indicated transformation of eu- and heterochromatin in condensed chromatin (heterochromatinization).
One of the potential epigenetic mechanisms is heterochromatinization of chromatin within the region of the genome containing a gene sequence, which inhibits any further molecular interactions with that underlying gene sequence and effectively inactivates that gene (Ellen et al. 2009
). The chromatin peak behavior described above shows progressive heterochromatinization of lymphocyte chromosomes from old individuals and confirms previously reported data (Lezhava 1984
). These significant changes in chromatin stability in old age indicate that the aging process involves transformation of the eu- and heterochromatin into condensed forms and that further compaction or progressive heterochromatinization occurs during aging.