Aging of lymphoid organs: Can photobiomodulation reverse age-associated thymic involution via stimulation of extrapineal melatonin synthesis and bone marrow stem cells?
- Department of Biomedical Engineering, Chinese University of Hong Kong, Hong Kong.
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
- Department of Dermatology, Harvard Medical School, Boston, MA, 02115, USA.
- Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, 02139, USA.
Thymic atrophy and the subsequent reduction in T cell production are the most noticeable age-related changes affecting lymphoid organs in the immune system. In fact thymic involution has been described as “programmed aging”. New therapeutic approaches such as photobiomodulation (PBM) may reduce or reverse these changes. PBM (also known as low-level laser therapy or LLLT) involves the delivery of non-thermal levels of red or near-infrared light that are absorbed by mitochondrial chromophores, in order to prevent tissue death and stimulate healing and regeneration. PBM may reverse or prevent thymic involution due to its ability to induce extrapineal melatonin biosynthesis via cyclic AMP or NF-kB activation, or alternatively by stimulating bone marrow stem cells that can regenerate the thymus. This perspective puts forward a hypotheses that PBM can alter thymic involution, improve immune functioning in aged people, and even extend lifespan.
The influence of pulsed infrared laser radiation on the hormone production in the thymus (an experimental study).
Local irradiation with pulsed (1500 Hz) low-energy infrared laser light of the thymus and thyroid gland region caused well-apparent stimulation of alpha-1-thymosin production in the healthy animals and normalized its level in the stressed ones. Similar stimulation of alpha-1-timosine biosynthesis was observed in an experiment with direct laser irradiation of the cultured HTSC epitheliocytes from the human thymus.
Adv Gerontol. 2010;23(4):547-53.
Induced thymus aging: radiation model and application perspective for low intensive laser radiation.
The influence of gamma-radiation on morphofunctional state of thymus is rather like as natural thymus aging. However gamma-radiation model of thymus aging widely used to investigate geroprotectors has many shortcomings and limitations. Gamma-radiation can induce irreversible changes in thymus very often. These changes are more intensive in comparison with changes, which can be observed at natural thymus aging. Low intensive laser radiation can not destroy structure of thymus and its effects are rather like as natural thymus aging in comparison with gamma-radiation effects. There are many parameters of low intensive laser radiation, which can be changed to improve morphofunctional thymus characteristics in aging model. Using low intensive laser radiation in thymus aging model can be very perspective for investigations of aging immune system.
Protective effect of low-power laser radiation in acute toxic stress.
The effect of preliminary short-term irradiation with He-Ne laser light (632.8 nm, 0.2 mW/cm2) of the thymus zone projection of male NMRI mice subjected to acute toxic stress on the responses of immune cells was studied. Stress was modeled by lipopolysaccharide injection, 250 mg/100 g of body weight, which induced a significant increase in the production of several macrophage cytokines, IL-1alpha, IL-1beta, IL-6, IL-10 and TNF-alpha. A single irradiation with laser light did not provoke considerable variations in NO production in cells but induced an enhancement in the production of heat shock proteins Hsp25, Hsp70, and Hsp90. Nevertheless, when irradiation with red laser light was applied prior to toxic stress, considerable normalization of production of nearly all cytokines studied and nitric oxide was observed. Moreover, the normalization of production of heat shock proteins has been shown in these conditions. Thus, preliminary exposure of a small area of animal skin surface provoked a significant lowering in the toxic effect of lipopolysaccharide.
Structure peculiarities of muscle regenerates and state of thymus under He-Ne laser therapy in different periods after muscle trauma.
We studied the gastrocnemius muscle regeneration and the reactive changes in thymus of rats under different regimens of He-Ne laser therapy of both operated legs (632.8 nm; 2.5-3.0 mW/cm(2) ). Laser radiation (10 exposures by 3 min within 1-15 days after muscle trauma, 4.5-5.4 J/cm(2) total dose per each leg) stimulated inflammatory reaction, muscle healing and favored preservation of muscle tissue in regenerates. The changes in thymus mass, its histological structure, size of cortex and thymocite mitotic index pointed to the increase of the functional load on thymus and delay of its recovery. The same dose of laser therapy of muscles within 16-30 days after trauma led to the increase of muscle tissue sclerotization in regenerates. The reactive changes in thymus were less pronounced. Threefold decrease of laser dose (10 exposures by 1 min for 1-15 days, 1.5-1.8 J/cm(2)) suppressed inflammatory reaction, impaired the muscle regeneration. The increase of functional activity in thymus was not observed.
Regeneration of skeletal muscles and state of thymus in gamma-irradiated rats under laser therapy of the area of muscle trauma.
A N Severtzov Institute of Ecology & Evolution, Russian Academy of Sciences, Moscow, Russia. firstname.lastname@example.org
The gamma-irradiation of adult rats with a semi-lethal dose (6 Gy) suppressed the posttraumatic regeneration of skeletal muscles and brought about considerable destructive changes in the thymus. The effect of He-Ne laser radiation at a total dose 4.5-5.4 J/cm2 at each operated leg in irradiated rats stimulated the regenerative capacity of skeletal muscle tissue, the healing of skin-muscle wound, and the processes of postradiation recovery in thymus cells (a decrease of chromosome aberrations). The histological structure of regenerates had more muscle pattern. At the same time, the positive dynamics of regenerative processes in muscles was achieved by an increased functional load on the thymus. To stimulate the regeneration of irradiated muscles on the background of a more moderate load on the thymus, the prolonged period of laser therapy and fragmentary distribution of laser exposures during muscle regeneration were preferable. Wound healing improved visibly. Nor formation of chronic radiation ulcers on operated shins was observed.
Effects of exposure of different skin areas to low-power laser light.
The effect of helium-neon laser light of extremely low power of 0.2 mW/cm2 and wavelength 632.8 nm on the immune status of mice bearing solid tumors was studied. The evaluation of the status of tumor-bearing animals was provided by taking into account the number of immune cells, cytokine concentration (tumor necrosis factor, interleukin 2, production of nitric oxide, expression of heat shock proteins (Hsp70 and Hsp90), and activity of natural killers. The model of a solid tumor was formed by subcutaneous injection of Ehrlich carcinoma cells, and average life span of tumor-bearing mice achieved about 55 days. Different areas of the skin of tumor-bearing mice were subjected either to a single (1 min, dose 0.012 J/cm3) or repeated exposure to laser light (1 min, 48-h intervals, 30 days). Two different areas were irradiated: the thymus projection area or a hind limb with solid tumors. The results showed that chronic exposure of tumor-bearing mice in the thymus projection area, and especially, hind limb, reduced the resistance, which manifested itself in the acceleration of tumor growth and a tendency of mouse life span to decrease. On the contrary, a single exposure stimulated the antitumor immunity for several days after the exposure. The results show the expediency of further investigation of the immunomodulative effects of low-power laser light and the necessity of monitoring the immune system during laser therapy.